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Hong Kong Baptist University
MASTER'S THESIS
Effects of osmotic stress on molecular responses of gill cells fromJapanese eels, Anguilla JaponicaHo, Cheuk Hin
Date of Award:2021
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Download date: 26 Jan, 2022
HONG KONG BAPTIST UNIVERSITY
Master of Philosophy
THESIS ACCEPTANCE
DATE: January 11, 2021 STUDENT'S NAME: HO Cheuk Hin THESIS TITLE: Effects of Osmotic Stress on Molecular Responses of Gill Cells from Japanese Eels,
Anguilla Japonica This is to certify that the above student's thesis has been examined by the following panel members and has received full approval for acceptance in partial fulfilment of the requirements for the degree of Master of Philosophy. Chairman: Prof Wong Ricky M S
Professor, Department of Chemistry, HKBU (Designated by Dean of Faculty of Science)
Internal Members: Prof Zhao Zhongying Professor, Department of Biology, HKBU (Designated by Head of Department of Chemistry) Prof Wong Chris K C Professor, Department of Biology, HKBU
External Examiner: Prof Wong Anderson On Lam Professor School of Biological Sciences The University of Hong Kong
Issued by Graduate School, HKBU
Effects of Osmotic Stress on Molecular Responses of Gill
Cells from Japanese Eels, Anguilla Japonica
HO Cheuk Hin
A thesis submitted in partial fulfilment of the requirements
for the degree of
Master of Philosophy
Principal Supervisor:
Prof. WONG Chris K C (Hong Kong Baptist University)
January 2021
! i!
DECLARATION+!
I!hereby!declare!that!this!thesis!represents!my!own!work!which!has!been!done!
after!registration!for!the!degree!of!MPhil!at!Hong!Kong!Baptist!University,!and!has!
not!been!previously!included!in!a!thesis!or!dissertation!submitted!to!this!or!any!
other!institution!for!a!degree,!diploma!or!other!qualifications.!
!
! ! I! have! read! the! University’s! current! research! ethics! guidelines,! and! accept!
responsibility! for! the! conduct! of! the! procedures! in! accordance! with! the!
University’s!Research!Ethics!Committee!(REC).!I!have!attempted!to!identify!all!the!
risks!related!to!this!research!that!may!arise!in!conducting!this!research,!obtained!
the!relevant!ethical!and/or!safety!approval!(where!applicable),!and!acknowledged!
my!obligations!and!the!rights!of!the!participants.!
!
!
!
!
!
! Signature:!___________________________!
! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Date:! January! 2021!
!
!
! !
! ii!
Abstract+
Japanese!eels!(Anguilla!japonicas)!are!snakelike!fishes!living!in!waters!in!the!
Asian!region.!In!contrast!to!most!fishes!which!are!stenohalines!that!can!only!live!
in!waters!with!a!narrow!range!of!salinity,!Japanese!eels!are!classified!as!
euryhalines!that!can!habitat!in!a!broad!range!of!salinity.!As!the!lifecycle!of!
Japanese!eels!consists!of!stages!across!fresh!and!seawater!districts,!a!wellS
developed!osmoregulation!mechanism!is!needed!to!balance!the!intraS!and!extraS!
cellular!osmolarity!of!the!fishes!throughout!the!seawater!acclimation!process.!
While!fish!gills!are!one!of!the!organs!that!separating!the!ambient!water!and!the!
inner!body!fluid!of!the!fish,!the!fish!gills!of!the!Japanese!eels!have!been!studied!
as!one!of!the!most!crucial!organs!for!osmoregulation!purposes.!Yet,!the!
osmoregulation!and!survival!strategies!of!Japanese!eels!under!hyperosmotic!
stress!has!not!been!fully!elucidated.!!
!
In!chapter!2,!this!study!has!performed!a!transcriptome!study!on!the!ex#vivo!gill!
filament!model!of!the!Japanese!eel!to!profile!the!molecular!responses!after!a!
hypertonic!treatment!of!4!hours!or!8!hours.!The!experiment!is!aimed!to!mimic!
the!gill!cells!exposed!to!seawater!in!the!seawater!acclimation!process!of!
Japanese!eels.!A!profile!of!differential!expressed!genes!(DEGs)!has!been!revealed!
that!577!DEGs!were!commonly!upregulated!and!711!DEGs!
were!commonly!downregulated!in!both!4S!and!8Shours!hypertonic!treatment.!
Functional!analysis!and!annotation!have!been!processed!with!these!DEGs,!
including!Ingenuity!Canonical!Pathways!analysis!and!gene!ontology.!These!
analyses!have!revealed!that!the!cellular!homeostasis!of!the!gill!cells!has!been!
disrupted!and!cell!death!responses!has!been!induced!by!osmotic!stress.!The!
! iii!
results!have!raises!a!concern!that!the!maintenance!of!cellular!viability!and!a!cell!
death!regulation!mechanism!are!needed!for!the!fishes!to!survive!in!the!early!
stage!of!seawater!acclimation.!
!
In!chapter!3,!this!chapter!demonstrated!that!gill!cells!in!Japanese!eels!are!
susceptible!to!apoptosis!when!they!are!exposed!to!hyperosmotic!treatments!in!
both!in!vitro!gill!cell!and!the!ex!vivo!gill!filament!model.!To!maintain!the!viability!
of!the!gills!cells,!two!inhibitors!of!apoptosis,!XIAP,!and!survivin,!were!seen!to!be!
expressed!in!gills!cells.!The!expression!of!XIAP!and!survivin!were!upregulated!by!
dexamethasone,!which!is!an!agonist!mimicking!the!effect!of!cortisol!on!fishes!in!
seawater!acclimation.!Meanwhile,!the!expression!levels!of!the!
apoptosis!executor,!caspase!3,!were!downregulated.!These!data!suggested!that!
with!the!regulation!of!cortisol!express!in!the!fishes,!XIAP!and!survivin!are!
effective!apoptosis!regulators!in!the!gill!cells!of!Japanese!eels.!
!
The!study!has!demonstrated!the!molecular!responses!of!the!gills!of!Japanese!eels!
exposed!to!hyperosmotic!stress!at!the!transcriptional!level!and!postStranslational!
level!by!using!transcriptome!studies!and!protein!study!respectively.!The!study!
has!paved!cell!death!regulation!to!be!another!the!key!field!to!study!in!
understanding!the!ability!of!salinity!tolerance!in!euryhalines.!!
!
! iv!
Acknowledgements+!
! ! I!would!like!to!express!my!sincere!gratitude!to!my!principal!supervisor,!Prof.!Chris!
KC!Wong! for! his! patience,! guidance,! and! encouragement! throughout!my! study!
period.!
! ! Besides,! I! would! like! to! express! my! thanks! to! Dr.! Ball! KP! Lai! from! the! City!
University!of!Hong!Kong!and!Dr.!William!KF!Tse!from!the!Kyushu!University!for!their!
guidance!and!support!on!my!research!work.! ! !
! ! I!would!like!to!extend!my!gratitude!to!Prof.!NS!Wong,!Dr.!Jamie!HT!Wan,!Dr.!Alice!
HM!Ng!and!Dr.!Cherry!CT!Leung!for!their!companionship!and!advice.! ! ! ! ! !
I!would!also!like!to!thank!all!scientific!officers!and!office!staff!in!the!Department!of!
Biology!for!their!technical!and!administrative!support.! !
! ! Last!but!not!least,!I!would!like!to!thank!Ms.!Sylvia!TW!Lau!and!my!family!for!their!
endless!support,!tolerance!and!unconditional!love.! !
!
!
!
! !
! v!
Tables+of+Contents+
DECLARATION+...................................................................................+i!
Abstract+...........................................................................................+ii!
Acknowledgements+........................................................................+iv!
Tables+of+Contents+...........................................................................+v!
List+of+Figures+...............................................................................+viii!
List+of+Tables+...................................................................................+ix!
List+of+Abbreviations+........................................................................+x!
Chapter+1+........................................................................................+1!Literature+Review+....................................................................................................+1!
1.!Eel!..........................................................................................................................!1!
1.1.)!Anguillid!eel!...............................................................................................................!1!
1.2)!Life!cycle!of!Anguilla#japonica!.....................................................................................!1!
2.!Fish!gills!..................................................................................................................!5!
2.1)!Structure!.....................................................................................................................!5!
2.2)!Gill!filament!.................................................................................................................!6!
2.3)!Gill!epithelium!and!gill!cell!..........................................................................................!7!
3.!Osmotic!and!salinity!stress!..................................................................................!11!4.!Cell!Death!............................................................................................................!12!
4.1)!Programmed!cell!death!and!apoptosis!.....................................................................!12!
4.2)!Caspases!....................................................................................................................!14!
4.3)!Inhibitors!of!apoptosis!(IAPs)!....................................................................................!16!
5.!Objectives!............................................................................................................!18!
Chapter+2+......................................................................................+19!Transcriptomic+Analysis+of+Ex#Vivo+Gill+Filaments+under+Hyperosmotic+Challenge+...+19!
2.1!Introduction!.......................................................................................................!19!Materials!and!Methods!...........................................................................................!21!
i)!Animal!...........................................................................................................................!21!
ii)!Ex#vivo!gill!filament!culture!..........................................................................................!21!
iii)!Osmotic!stress!induction!treatment!............................................................................!21!
! vi!
iv)!RNA!isolation!and!quantification!.................................................................................!23!
v)!Transcriptome!sequencing!...........................................................................................!23!
vi)!DEGs!Functional!annotation!........................................................................................!23!
vii)!RealStime!PCR!analysis!...............................................................................................!24!
2.3!Results!...............................................................................................................!25!
i)!Transcriptome!revealed!DEGs!in!ex#vivo!gill!filament!culture!upon!hyperosmotic!stress
!.........................................................................................................................................!25!
ii)!Functional!analysis!.......................................................................................................!26!
2.4!Discussion!..........................................................................................................!33!
i)!Acute!osmotic!stress!induces!a!broad!set!of!dysregulated!genes!.................................!33!
ii)!Acute!osmotic!stress!did!not!induce!the!expression!of!ion!transporters!.....................!33!
iii)!Enhanced!tgfb3#expression!evidenced!SW!acclimation!process!in!the!ex#vivo#gill!model
!.........................................................................................................................................!34!
iv)!Osmotic!stress!showed!disruptions!to!cellular!homeostasis,!and!trigger!cell!death!
responses!in!Japanese!eel!................................................................................................!34!
v)!Enriched!molecular!function!lied!clues!for!the!molecular!mechanism!that!interrupted!
translation!process!or!protein!synthesis!..........................................................................!35!
2.5!Summary!............................................................................................................!37!
Chapter+3+......................................................................................+38!The+AntiLapoptotic+Role+of+Dexamethasone+on+Gill+cells+upon+Osmotic+Challenge+..+38!
3.1!Introduction!.......................................................................................................!38!Materials!and!Methods!...........................................................................................!40!
i)!Animal!...........................................................................................................................!40!
ii)#In#vitro#primary!gill!cell!culture!....................................................................................!40!
iii)!Ex#vivo#gill!filament!culture!.........................................................................................!41!
iv)!Hormonal!treatment!and!osmotic!stress!induction!treatment!...................................!41!
vi)!Protein!extraction!and!western!blot!...........................................................................!42!
3.3!Result!.................................................................................................................!43!
! vii!
In#vitro#gill!cell!model!...............................................................................................!43!
i)!Hyperosmotic!stress!reduced!the!viability!of!gill!epithelial!cells!..................................!43!
ii)!Hyperosmolarity!triggered!the!activation!of!apoptotic!executor!caspase!3!................!43!
iii)!The!SW!acclimation!hormone!cortisol!reduced!the!level!of!cleaved!caspaseS3!
expressions!in!SW!acclimating!gill!cells!............................................................................!44!
Ex#vivo!gill!filament!model!.......................................................................................!50!
iv)!Ex#vivo!gill!filament!culture!model!showed!proScaspaseS3!cleavage!and!the!expression!
of!inhibitors!of!apoptosis!induced!by!osmotic!treatment!................................................!50!
v)!Dexamethasone!reduced!caspaseS3!cleavage!and!induced!the!expression!of!XIAP!and!
survivin!in!ex!vivo!gill!filament#model!under!hypertonic!treatment!................................!50!
3.4!Discussion!..........................................................................................................!53!
i)!Hypertonicity!activates!proScaspaseS3!cleavage!and!apoptosis!....................................!53!
ii)!Dexamethasone!diminished!the!threat!of!apoptosis!in!gill!cells!under!hyperosmotic!
treatment!.........................................................................................................................!54!
iii)!Expression!of!inhibitors!of!apoptosis!were!induced!by!osmotic!pressure!..................!55!
iv)!Dexamethasone!prompts!the!expression!of!both!XIAP!and!survivin!in!the!ex#vivo#gill!
filament!culture!under!hypertonic!treatment!..................................................................!56!
3.5!Summary!............................................................................................................!58!
Appendix+.......................................................................................+59!
Bibliography+................................................................................+230!
CURRICULUM+VITAE+.....................................................................+248!! +
! viii!
List+of+Figures+!
Fig.!1.1! A!schematic!diagram!of!the!anatomy!of!fish!gill!
Fig.!2.1! A!schematic!diagram!of!the!workflow!of!the!study!
Fig.!2.2! Valcano!plots!of!DEGs!identified!from!the!ex#vivo!culture!
model!after!4S!(upper)!and!8S!hours!(lower)!hypertonic!
stress!induction!
Fig.!2.3! Venn!diagram!showed!comparison!between!the!DEGs!from!
4S!and!8S!hours!hypertonic!treatment!
Fig.!2.4! Transcriptome!data!validation!by!qPCR!
Fig.!2.5! Bar!chart!showing!the!significance!of!the!top!20!enriched!
Ingenuity!Canonical!Pathways!
Fig.!2.6! Gene!ontology!analysis!of!common!DEGs!by!DAVID!
Fig.!3.1! Cell!morphology!after!exposure!to!various!osmotic!stress!for!
1!hour!
Fig.!3.2! In# vitro# primary! gill! cell! culture! showing! cleavage! of! proS
caspase3!and!PARP!under!hypertonic!stress.!
Fig.!3.3! DEX!effect!on!cells!treated!with!osmotic!treatment!
Fig!3.4! DEX!showed!reduction!on!the!expression!of!cleaved!caspase!
3!in!1!hour!hypertonic!treatments!
Fig!3.5! The!effect!of!10!uM!DEX!on!gill!cells!in!hypertonicity!
Fig!3.6! Western! blot! of! ex# vivo! gill! filament! culture! in! osmotic!
treatment!for!8!hours!
Fig!3.7! Western! blot! of! ex# vivo! gill! filament! culture! after! 8! hours!
osmotic!pressure!exposure!and!dexamethasone!treatment!
!!
! ix!
List+of+Tables+!
Table 2.1 Nucleotide!sequence!of!the!gene!specific!primers!used!
Supplementary Table 1 Commonly upregulated DEG from transcriptome analysis
Supplementary Table 2 Commonly downregulated DEG from transcriptome analysis
Supplementary Table 3 Enriched Ingenuity Canonical Pathways
!
!
!
!
!
! !
! x!
List+of+Abbreviations+!
ACs! ! Accessory!cells!
ATP! ! Adenosine!triphosphate!
CCs! ! Chloride!cells!
CFTR! ! Cystic!fibrosis!transmembrane!regulator!
DAVID!! The!Database!for!Annotation,!Visualization!and!Integrated!Discovery!
DEGs! ! Differential!expressed!genes!
DEX! ! Dexamethasone!
DMSO!! Dimethyl!sulfoxide!
EDN1! ! EndothelinS1!
EGF! ! Epidermal!growth!factor!
EPC! ! Epithelioma!papulosum!cyprini!
FBS! ! Fetal!bovine!saline!
FW! ! Freshwater!
GO! ! Gene!ontology!
GR! ! Glucocorticoid!receptor!
IAPs! ! Inhibitors!of!apoptosis!
IGFS1! ! Insulin!growth!factor!1!
ITS! ! Insulin!transferrin!selenium!
MRCs! ! Mitochondrion!rich!cells!
NCCD! ! Nomenclature!Committee!on!Cell!Death!
NKA! ! Na/K+SATPase!
NKCC! ! Na/K/ClScoStransporter!
Ostf1! ! Osmotic!stress!transcription!factor!1!
P/S! ! PenicillinSstreptomycin!
! xi!
PBS! ! Phosphate!buffered!saline!
PCD! ! Programmed!cell!death!
PPT! ! Parts!per!thousand!
PVCs! ! Pavement!cells!
RA! ! ReninSangiotensin!
RF! ! Release!factor!
!
! 1!
Chapter+1++
Literature+Review++
1.+Eel+!
1.1.)+Anguillid+eel+ +
!
Eels!are! snakelike! teleost! fishes!characterized!by! the!absence!of!pelvic! fins!and!
scales.!The!fish!belong!to!the!order!of!Anguilliformes,!which!consist!of!4!suborders,!
20! families,! 111! genera! and! about! 800! species.! Eels! inhabit! almost! all! waters,!
including! oceans,! rivers,! lakes,! or! estuaries.! Nevertheless,! members! from! the!
family! Anguillida! are! the! only! types! of! eels! mature! in! freshwater.! The! family!
Anguillida!includes!19!existing!species!and!six!subspecies.!All!family!members!are!
catadromous,! for! example,! Auguilla# anguilla! (European! eel),! Anguilla# rostrata!
(American! eel),! and! Anguilla# japonica! (Japanese! eel).! These! species! share! a!
peculiar! life!cycle!as! the! larva!spawn! in!seawater!and!migrate!to! freshwater! for!
maturation!(Berg,!1958),!and!return!to!their!seawater!spawning!spot!to!mate.! ! ! !
!
1.2)+Life+cycle+of+Anguilla(japonica+ +
! !
Anguilla#japonica,!also!known!as!the!Japanese!eels,!are!members!of!the!Anguillid!
eel!distributing!in!Asian!waters,!near!Japan,!Korea,!Taiwan,!Vietnam,!and!northern!
Philippines!(Masuda!et!al.,!1984).!Due!to!their!catadromous! life!cycle,! Japanese!
eels! at! different! developmental! stages! inhabit! in! seawater,! brackish!water,! and!
freshwater!regions!(Riede,!2004).!
!
!
! 2!
Japanese!eels!are!oviparous.!Mature!Japanese!eels!migrate!from!freshwater!to!the!
ocean!and!spawn!eggs!before!the!new!moon!period!of!May!to!August!(Cheng!&!
Tzeng,!1996;!Ishikawa!et!al.,!2001;!Han!et!al.,!2012).!The!spawning!area!was!first!
suggested! in! 1991!with! the! discovery! of! the! flat! and! transparent! larva! of! eels,!
leptocephali,!at!the!junction!of!the!Suruga!Seamount!and!along!the!West!Marina!
Ridge! (14–17°! N,! 142–143°! E)! (Tsukamoto,! 1992).! The! research! team! further!
narrowed!the!spawning!area!in!2005!with!the!identification!of!the!immature!larva!
of!eels,!preleptocephali!at!2S5!days!old,!in!the!same!region!(Tsukamoto,!2006).!In!
2009,!wild!Japanese!eel’s!egg!was!first!collected!at!the!same!location!and!finally!
concluded!the!exact!spawning!spot!of!Japanese!eel!(Tsukamoto!et!al.,!2011).! !
!
The!eggs!of!Japanese!eel!hatch!within!27S32!hours!postSfertilization!at!an!optimum!
temperature!around!25!°C!(Ahn!et!al.,!2012).!Newly!hatched!larvae!are!known!as!
the! preleptocephali! at! about! 3.6! mm! in! length.! The! preleptocephali! mainly!
consume! planktons! or! other! delicate! organic! residues! and! grow! into! the!
leptocephali!stage! in!a! few!days! (Aoyama!et!al.,!2001;!Tanaka!et!al.,!2001).!The!
leptocephali!then!swim!along!the!North!Equatorial!Current!from!the!spawning!spot!
and!enter!the!Kuroshio!Current!(Cheng!et!al.,!1996;!Han!et!al.,!2012;!Tsukamoto,!
2006).! ! The! leptocephali! are! drifted! along! with! the! Kuroshio! Current! to! their!
freshwater! habitation! continents! (Tzeng,! 2003).! During! the! 4S8!months! drifting!
period,! the! leptocephali! enter! the! first!metamorphosis! and! transform! into! the!
glass!eel!stage.!This!threeSweek!metamorphosis!process!is!featured!by!a!dramatic!
change!of!physique,! from!the!flat! leafSlike!shape!body!to!a!round!and!snakelike!
appearance! (Tabeta! &!Mochioka,! 2003).! The! newly!metamorphosed! glass! eels!
(~65mm)!swam!further!inland!to!freshwater!estuaries!or!rivers!to!explore!suitable!
habitats!and!entered!the!next!growth!stage!known!as!the!elver!stage!(Paxton!&!
!
! 3!
Eschmeyer,!1998).!Eels!at!the!elver!stage!gain!an!increasing!amount!of!pigment!for!
better! camouflage.! Diets! on! shrimps,! aquatic! insects,! crustaceans,! and! other!
invertebrates,!eels!eventually!grow!into!the!yellow!eel!stage,!which!is!the!longest!
maturing!stage!in!the!lifecycle!of!Japanese!eels!(Bertin,!1956;!Lamothe!et!al.,!2000;!
Strubberg,!1913;!Tesch,!2003).!The!yellow!eel!stage!of!Japanese!eels!begins!with!
the!sign!of!the!development!of!golden!pigment.!This!stage!can!last!for!five!years!or!
even!longer!until!the!onset!of!sexual!maturation!(Fukuda!et!al.,!2013;!Han!et!al.,!
2003;! Tzeng,! 2000).! Japanese! eels! in! the! yellow! eel! stage! gain! a! significant!
increment!in!body!size!and!start!producing!mucus!from!the!skin!cell.!The!yellow!
eel! stage! terminates!with! the! second!metamorphosis! known!as! the! “silvering.”!
Japanese!eels! in! the!silvering!process!undergo!a!visible!change! in!pigmentation!
with!their!dorsum!turn!darker,!and!the!ventral!part!becomes!silvery!(Durif!et!al.,!
2005;!Okamura!et!al.,!2007).!The!silvering!stage!indicates!that!the!Japanese!eels!
are!sexually!mature!and!will!soon!begin!a!long!migration!towards!their!birthplace!
for!mating!and!giving!birthing!to!the!next!generation!(Han!et!al.,!2003;!Lokman!&!
Young,!1998).! !
! !
The!voyage!back!to!the!ocean!is!the!final!stage!of!the!lifecycle!of!Japanese!eel.!Eels!
stop!their!ingestion!behaviors!in!the!journey!and!obtain!energy!by!consuming!their!
body! fat.!Due! to! the! loss!of! functions,! the!guts! and! the! teeth!are!degenerated!
(Panhurst! &! Sorensen,! 1984;! Tsukamoto! et! al.,! 2011).! The! fish! develop! both!
morphological! and! physiological! modifications! to! adapt! to! the! seawater!
environment.!For!example,! the!development!of!more!enormous!eyes,!deepSsea!
vision!(increase!sightSsensitivity!from!red!to!blue!spectrum),!an!increment!in!the!
integument!thickness!to!withstand!a!higher!water!pressure,!and!the!rising!density!
of! gill! chloride! for! hyperosmoregulation! (Beatty,! 1974;! Fontaine! et! al.,! 1995;!
!
! 4!
Sorensen!&!Pankhurst,!1988).!Japanese!eels!are!terminal!breeders,!and!they!die!
after!mating!and!spawning!(Tesch!1977;!Tsukamoto!1992).!The!eggs!hatch!within!
a!week,! and! the! larvae! start! their! long! journey! towards! fresh!waters! like! their!
ancestors.! The! euryhaline! life! cycle! of! Japanese! eels! has! demonstrated! their!
astonishing! ability! to! accommodate! a!wild! range! of! salinity! and! cope!with! the!
osmotic! stresses,! making! Japanese! eels! to! be! a! perfect! model! for! studying!
osmoregulation! and! to! understand! cellular! survival! strategies! against! osmotic!
stress.! !
! !
!
! 5!
2.+Fish+gills+!
2.1)+Structure+!
Gill! is!a!complex!tissue!unique!in!aquatic!organisms.!It! is!responsible!for!various!
vital! functions! such! as! ventilation,! osmoregulation,! acidSbase! regulation,! and!
nitrogen!waste!excretion!of!fishes!(Evans!et.!al,!2005;!Hughes,!1958).!Anatomically,!
fish!gills!serve!as!a!physical!barrier!separating!the!external!environment!and!body!
milieu!of!fishes.!Gill!epithelia!directly!contact!with!the!ambient!water!at!the!apical!
side,! and! with! blood! capillaries! at! the! basal! side! (Olson,! 2002).! Teleost! fishes!
consist!of!two!separate!sets!of!gills!locating!at!both!sides!of!the!pharynx.!The!gills!
are!protected!by!the!coverage!of!a!thin!bony!layer!known!as!the!opercula!(Charles!
et! al.,! 2008).! Fish! gills! have! a! highly! differentiated! structure! to! maximize! its!
functional!surface!area!for!gaseous!exchange!and!osmoregulation.!Each!set!of!gills!
comprise!of!four!pairs!of!holobranch!gills!(Wilson!&!Laurent,!2002).!The!gill!arch!
bone! and! gill! filaments! together! form! the! differentiated! structure! called! the!
holobranch! gills.! A! branchial! afferent! artery! and! an! efferent! branchial! artery!
perfuse!the!arch!bones!of!the!holobranch!gills!and!gill! filaments!for!oxygen!and!
nutrient! transport,! as! well! as! to! remove! CO2! and! nitrogenous! wastes.! Each!
holobranch! gill! can! be! further! divided! into! two! hemibranch! gills,! which! are!
supported!by!two!independent!interbranchial!septa!extended!from!the!arch!bone!
to!the!base!of!the!gill!filaments!to!enhance!free!movement!of!the!gill!(Robert!et!
al.,!2015)!(Fig.!1).! !
! !
!
! 6!
2.2)+Gill+filament+ +!
Gill! filaments! are! villi! like! extensions! connecting! with! the! gill! arches.! All! gill!
filaments!are!covered!with!discSshaped,!flatted!structures!known!as!the!lamellae.!
The!lamellae!are!the!basic!functional!unit!of!fish!gills!and!can!be!further!divided!
into! two! parts:! the! primary! lamellae! and! the! secondary! lamellae.! The! primary!
lamellae! are! located!at! the! terminal! septal! end!of! the! secondary! lamellae.! The!
primary!lamellae!function!as!the!major!sites!for!vascular!perfusion!that!regulate!
blood!flow!between!the!afferent/!efferent!branchial!artery!and!the!capillaries!in!
the!secondary!lamellae!(Laurent!&!Dunel,!1980).!The!secondary!lamellae!are!flat!
plates! allocated!on! the! filaments! to! function!as! the! sites! for! gaseous! and! ionic!
exchange.! They! arrange! perpendicularly! along! the! surface! on! every! filament,!
creating!regular!spaces!between!each!other!and!forming!channels! to!direct! the!
water!passing!through!gill!filaments.!This!arrangement!of!the!secondary!lamellae!
extensively!enlarges!the!surface!area!for!gaseous!and!ion!exchange!between!the!
fish! gill! and! the! ambient! water! (Huges,! 1966).! The! intraSlamellar! blood! flow!
circulates! in! the! opposite! direction! from! the! external!water! flow! to! produce! a!
countercurrent! and! enhance! the! efficiency! of! material! exchange! between! the!
external!environment!and!the!gills!(Evans!et!al.,!2005).!The!highly!differentiated!
structures! and!morphological! features! highly! expedite! the! functions! of! the! gill.!
These!also!provide!a!larger!surface!area!for!the!attachment!of!the!gill!epithelial!cell!
layer.! ! ! ! !
!
!
! 7!
!+
Fig.+1.1+A+schematic+diagram+of+the+anatomy+of+a+fish+gill.+
The!red,!purple,!and!blue!arrows!represent!the!flow!direction!of!oxygenated!blood!
(OB),! deoxygenated! blood! (DOB),! and! the! ambient! water,! respectively.! The!
enlarged!window!shows!the!blood!flow!in!the!secondary!lamella!(figure!modified!
from! AS! biology! Ms! Timms.! (2013).! Structure! of! fish! gill.! Retrieved! from!
http://mstimmSasbiology.blogspot.com/2013/02/structureSofSfishSgills.html).! !
+
2.3)+Gill+epithelium+and+gill+cell+
!
The!gill!epithelial!layer!composes!of!several!cell!types!(i.e.,!pavement!cells,!chloride!
cells,! and!accessory! cells)!differentiated! from! the!multipotent! cells! in! the! inner!
layer!of!primary!lamellae!(Laurent,!1984;!Morgan,!1974;!Olsom,!2002).!Pavement!
cells!(PVCs)!are!the!most!abundant!cell!type,!contributing!over!90%!of!the!total!cell!
population!of!the!epithelia.!Morphologically,!PVCs!feature!a!large!polygonal!apical!
surface! covering! with! microSridges! that! form! concentric! circular! structures! to!
increase!the!contact!surface!area!of!PVCs!with!the!ambient!water!(Wong!&!Chan,!
!
! 8!
1999;!Wilson!&!Laurent,!2002).!The!functions!of!PVCs!may!vary!among!different!
types!of!fishes.!Immunohistochemistry!showed!the!presence!of!proton!pumps!in!
gill!PVCs!of!rainbow!trout!(Oncorhynchus#mykiss)!to!support!its!role!in!acidSbase!
and! ion! regulatory! functions! (Sullivan! el! al.,! 1995).! Under! carbon! dioxide! and!
alkaline!exposure,!PVCs!show!a!morphological!alteration!in!increasing!the!density!
of! microSridges! on! the! apical! surface,! suggesting! the! facilitation! of! ionS
transportation!and!acidSbase!balance!(Gross!et!al.,!1994;!Laurent!et!al.,!2000).!In!
euryhaline! fishes,! PVCs! in! rainbow! trout!were! found! to! be! responsible! for! the!
uptake!of!calcium!ion!when!the!number!of!chloride!cells!was!low!(MacKenzie!&!
Perry,! 1997).! In! nonSteleost! fishes,! a! high! concentration! of! mucous! secretory!
granules! has! been! found! in! the! apical! cytoplasm! of! the! PVCs,! suggesting! that!
mucus!secretion!is!also!one!of!the!functions!of!PVCs!(Bartels,!1985;!Laurent,!1984;!
Mallatt!&!Paulsen,!1986).!In!Japanese!eel,!a!transcriptome!study!has!revealed!the!
gene!expression!profile!of!PVCs.!Specific!differential!expressed!genes!(DEGs)!with!
14!enriched!signaling!pathways!were!identified,!including!the!prolactin!signaling!
and!insulin!growth!factor!1!(IGFS1)!signaling!pathway!(Lai!et!al.,!2015).!Prolactin!
signaling!was!reported!to!regulate!freshwater!acclimation!in!fishes!(Evans!et!al.,!
2005).!The!IGFS1!signaling!pathway,!also!known!as!the!growth!hormone!pathway,!
was!reported!as!the!regulator!of!Na+/K+SATPase!(NKA)!under!seawater!acclimation!
(McCormick,! 2001).! These! studies! suggested! that! PVCs! are! responsible! for!
hormonal!response!to!regulate!osmoregulation!in!Japanese!eels.!
!
Chloride!cells! (CCs)!are!named!as! ionocytes!or!mitochondrionSrich!cells! (MRCs).!
CCs! are! characterized! by! a! high! number! of! mitochondria! for! adenosine!
triphosphate!(ATP)!synthesis!to!support!active!ion!transport!(Claiborne!et!al.,!2002;!
van!der!Heijden!et!al.,!1997).!CCs!and!their!subtypes!only!composed!less!than!10%!
!
! 9!
of!the!total!cell!population!in!the!gill!epithelia.!Due!to!their!essential!and!distinctive!
role!in!chloride!ion!excretion!in!seawater!teleosts,!CCs!were!one!of!the!major!study!
targets!for!understanding!gill!functions!(Marshall!et!al.,!2002).!The!majority!of!CCs!
locate!in!the!interSlamellar!space.!The!apical!membrane!of!CCs!varies!from!concave!
to!convex!shape!and!is!covering!by!microvilli!at!the!apical!surface.!Generally,!CCs!
acquire! a! distinct! feature! of! an! intracellular! tubulovesicular! system,! which! is!
independent!of!the!Golgi!apparatus!(Wilson!&!Laurent,!2002).!A!high!abundance!
of! Na+/K+SATPase,! which! are! highly! dependent! on! ATP! for! its! function! of! ion!
transportation,!is!associated!with!the!tubulovesicular!system!(Marshall!et!al.,!2002!
and!Sardet!et!al.,!1979).!The!expression!of!three!primary!protein!transporters!for!
salt! secreting,! including! Na+/K+SATPase! a1b,! NaSKSCl! cotransporter! (NKCC)! and!
cystic! fibrosis! transmembrane! regulator! (CFTR),!were! upregulated! by! the! IGFS1!
(Pelis!&!McCormick,!2001;!Tipsmark!&!Madsen,!2009).!The!functions!of!active!ion!
transportation!by!CCs!are!highly!associated!with!the!ambient!salinities!and!so!the!
ion!gradient!across!the!extracellular!and!intracellular!compartments!(Perry,!1997;!
Evans!et!al.,!1999).!CCs!are!involved!in!the!active!ion!excretion!of!excessive!sodium!
ion!in!seawater,!but!the!uptake!of!sodium,!calcium,!and!chloride!ions!in!freshwater!
environments.!Transcriptome!profile!of!Japanese!eel!has!revealed!12!CCs!specific!
expressed! pathways,! including! endothelinS1! (EDN1),! epidermal! growth! factor!
(EGF),!and!reninSangiotensin!(RA)!signaling!(Lai!et!al.,!2015).!These!three!pathways!
are!all! relating! to! the! ion! transport! function!of!CCs.!EDN1! is!known!to! regulate!
chloride!ion!transportation!in!teleost!fish,!with!its!expression!upregulated!during!
seawater!acclimation!(Hyndman!&!Evans,!2007).!The!EGF!signaling!pathway!has!
reported! being! responsible! for! cell! volume! regulation! and! ion! balance! under!
hypertonic!stress!(Brown!&!Baumgarten,!2006).!In!eels,!RA!signaling!plays!a!role!in!
epithelial! sodium! ion! transportation! and! controlling! their! blood! pressure! and!
!
! 10!
drinking!behavior!(Marsigliante!et!al.,!1997;!Tierney!et!al.,!1995).! !
!
Accessory!cells!(ACs)!are!another!type!of!gill!epithelial!cell!containing!a!high!density!
of!mitochondria!but!having!a!less!developed!tubulovesicular!system!in!contrast!to!
CCs.! ! Comparatively,!ACs!contain!a!lower!level!of!Na+/K+!ATPase!and!are!smaller!
in! size! (Hootman! &! Philpott,! 1980).! ACs! mostly! locate! at! the! surface! of! the!
epithelial! layer.! ! Intriguingly,!ACs! show!a!close! functional! connection!with!CCs,!
evidenced!by!its!cytoplasmic!processes!connected!to!the!apical!surface!of!CCs!to!
form!an!intricate!mosaic!establishment.!The!structure!shows!practical!importance!
in!the!paracellular!sodium!ion!efflux,!which!facilitates!the!apical!chloride!ion!efflux!
(Marshall!et.! al,!2002).!ACs!are!discovered! in! freshwater!euryhaline!by!osmium!
staining!(Pisam!et!al.!1988;!Pisam!et!al.!1989;!Pisam!1990).!Yet,!the!functions!of!
ACs! are!not! fully! characterized.!Wendelaar! et! al.! (1989)! suggested!ACs! are! just!
immature!MRCs!at! the!early!developmental! stages.!Nevertheless,!Laurent!et!al.!
(1995)!reported!the!identification!of!seawater!ACs!in!tilapia!in!an!alkaline!lake!(pH!
10)!in!associated!with!CCs!to!process!the!paracellular!sodium!ion!efflux!while!CCs!
were! excreting! hydrogen! carbonate! ions.! The! study! proposed! the! rapid! ion!
pumping!function!of!ACs!is!critical!to!immediate!tolerance!of!ambient!salinity!and!
pH!stresses.! !
With!hindsight,! fish!gills!have!shown!to!be!a!physiologically! important! tissue!to!
regulate! the! vital! processes! in! fishes,! supporting! gaseous! exchange! and! ionS
osmoregulation.! Having! the! ability! to! habitat! in! both! fresh! and! seawater!
environment,!the!gills!of!Japanese!eels!are!one!of!the!best!models!to!understand!
the!working!mechanism!of!osmoregulation!of!teleosts.! ! !
! !
!
! 11!
3.+Osmotic+and+salinity+stress+!
Different! from!stenohaline! fishes! that!only! live! in!waters!with!a!stable! range!of!
salinity,!euryhaline!fishes!can!habitat!in!waters!with!a!wide!range!of!salinity.!In!the!
life! cycle! of! Japanese! eels,! mature! eels! migrate! from! freshwater! back! to! the!
seawater!mating!spot.!The!salinity!ranges!from!<0.5!parts!per!thousand!(ppt)! in!
freshwater! to! about! 30S40! ppt! in! seawater.! At! the! same! time,! the! salinities! of!
brackish!water!in!the!estuary!can!vary!from!0.5!to!35!ppt!(IAL!&!IUBS,!1958).!The!
varying!salinities!in!estuaries!and!intertidal!zones!can!impose!great!osmotic!stress!
on!fishes.!An!effective!and!efficient!osmoregulation!system!is!thus!necessary!to!
stabilize! body! ion! and! water! concentration! (Marshall,! 2013).! Considerable!
molecular! and! cellular! changes! in! fish! gills! are! known! as! critical! biological!
processes! to! restore! electrolyte! balance! and! is! indispensable! for! cell! survival!
(Karnaky!et!al.,!1976;!Kültz!et!al.,!1992;!Laverty!&!Skadhauge,!2012).!A!failure!of!
osmoregulation! would! lead! to! an! osmotic! imbalance,! perturbing! normal!
physiological!processes,!and!leading!to!cell/tissue!damage!(Hashimoto!et!al.,!1998).!
For! example,! salinity! stress! can! induce! oxidative! damage! via! the! generation! of!
reactive!oxygen!species!and!apoptosis!(RiveraSIngraham!et!al.,!2016).!As!Japanese!
eels! can! adapt! to! varying! water! salinities,! their! competence! affirms! the! high!
efficiency! in! the! prevention! of! cell! and! tissue! damage! under! osmotic! stresses.!
Therefore,! fish!gill! cells!are!programmed! to!maintain!cellular!milieu!against! the!
changing!osmotic!conditions!in!the!water.!
! !
!
! 12!
4.+Cell+Death+ +!
Cells!are!the!basic!functional!units!of!living!organisms.!Maintenance!of!the!cells!in!
their! optimum! state! is! thus! imperative.! Nevertheless,! cells! are! constantly!
challenged! by! different! stresses! that! can! induce! cell! damage/death.! There! are!
various!forms!of!cell!death!mechanism,!and!those!can!be!categorized!according!to!
four!aspects:!1)!The!morphological! features;!2)! the!enzymological! requirements!
for!the!process,!for!example,!the!involvement!of!nucleases!and!proteases;!3)!the!
functions! and! causations! to! evaluate! whether! the! cell! death! events! are!
programmed! or! accidental,! and! physiological! or! pathological;! and! 4)! the!
immunological! characteristics! (Kroemer! et! al.,! 2009).! The! Nomenclature!
Committee!on!Cell!Death!(NCCD)!has!proposed!a!precise!classification!and!stages!
of! different! types! of! cell! death,! mainly! including! apoptosis,! autophagy,! and!
necrosis!(Kroemer!et!al.,!2005).! !
!
4.1)+Programmed+cell+death+and+apoptosis+ +
Compare!to!the!accidental!cell!death!incident!of!necrosis,!programmed!cell!death!
(PCD)! is! regulated!by!a! series!of! cellular!events! involving!both!biochemical! and!
morphological!alterations!(Ameisen!et.!al,!2002;!2004;!Kroemer!et!al.,!2005).!This!
process! removes! unwanted,! nonSfunctional,! or! damaged! cells! that! cannot! be!
rescued! (Jacobsen! et! al.,! 1997).! PCD! has! shown! to! be! crucial! in! different!
developmental!processes!in!various!species.!In!Drosophila,!the!inhibition!of!PCD!
has! caused! malformation! and! organismal! lethality! on! physiological! structure,!
including! legs,! wings,! eyes,! genitalia,! digestive! system! and! the! nervous! system!
(White!et!al.,!1994,!Grether!et!al.,!1995,!Xu!et!al.,!2005,!Srivastava!et!al.,!2007).!In!
vertebrates,! Kerr! at! al.! (1972)! revealed! a! type! of! PCD! with! morphological!
distinctiveness! known! as! “apoptosis.”! The! sign! of! apoptosis! were! reported! in!
!
! 13!
nearly!all!developmental!process.! ! For!example!the!differentiation!of! the! inner!
cell!mass!of!blastocytes,!and!the!stabilization!of!tissue!homeostasis!by!removing!
cells!with!a!slower!growth!or!potential!harmful!effect.!Through!the!head!involution!
defective! (HID)! meditated! apoptosis,! the! process! arrested! cells! from! further!
multiplying!and!spreading!(de!la!Cova!et!al.,!2004;!Moreno,!2008).! !
!
Despite! the! internal! developmental! signals,! PCD! can! be! triggered! by! external!
abiotic! stresses! (Beers! &! McDowell,! 2011).! Although! necrosis! is! the! nonS
physiological! type! of! cell! death! in! extracellularSabioticSstressStolerating! cells,!
abiotic!stressSinduced!PCD!activities!have!been!reported!in!cells!of!plants,!fishes!
and!mammals!(AnvariFar!et!al.,!2017;!Ferraro!&!Cecconi,!2007;!Kvitt!et!al.,!2016;!
Lennon!et!al.,!1991;!Petrov,!2015).!In!fishes,!apoptosis!is!induced!under!osmotic!
stress! and! directly! distorted! cellular! homeostasis! (Hashimoto! et! al.,! 1998).! In!
addition,! apoptosis! also! functions! as! an! immune! strategy! to! remove! nonS
repairable! cells! caused! by! disease! or! pernicious! agents! (Norbury! and! Hickson,!
2001).! !
!
Although!the!threshold!level!of!stimulus!causing!apoptosis!varies!among!cell!types,!
the!morphological! features!of!cells!undergoing!apoptosis!are! the!same!(Hacker,!
2000;!Kerr!et!al.,!1972).!Apoptosis!is!first!featured!with!cell!shrinkage!and!pyknosis.!
The!process! is!then!followed!by!the!breakdown!of!plasma!and!the!formation!of!
apoptotic!bodies.!The!apoptotic!bodies!contain!part!of!the!cytoplasm!with!packed!
organelles!and!nucleic!fragments.!The!presence!of!apoptotic!bodies!indicates!the!
execution!phase!of!the!apoptosis,!and!the!apoptotic!bodies!will!eventually!engulf!
by!phagocytes!(Elmore,!2007).!Different!from!other!types!of!cell!death,!apoptosis!
does! not! cause! inflammatory! response! as! the! process! does! not! involve! the!
!
! 14!
breakdown! of! cells! and! the! leakage! of! the! inner! cellular! components! into! the!
surrounding! interstitial! tissue.! The! phagocytes! do! not! produce! any! antiS
inflammatory!cytokines!in!the!phagocytic!process!as!well!(Kurosaka!et!al.,!2003;!
Savill! and! Fadok,! 2000).! These! make! the! unique! psychological! features! in!
identifying!an!apoptosis!cell!death!from!necrosis.! !
!
On!the!aspect!of!biochemical!features,!apoptosis!is!a!highly!sophisticating!process!
that! involves! a! series! of! energySdependent! biochemical! modifications.! Protein!
cleavage,!proteins!crossSlinking,!DNA!fragmentation,!and!recognition!of!phagocytic!
activities!are!the!biochemical!characteristic!in!apoptotic!cells!(Hangartner,!2000).!
Two!distinct!types!of!apoptotic!pathways,!the!intrinsic!and!extrinsic!pathway,!have!
been! recognized! with! specific! initiators! in! each! pathway.! Nevertheless,! both!
pathways!have!shown!to!be!linked!and!share!some!common!biomolecules!(Igney!
and!Krammer,!2002).! !
!
4.2)+Caspases+ +!
Apoptosis!is!dependent!on!a!protease!cascade!involving!the!caspase!protein!family.!
Caspases!are!the!major!biomolecules!responsible!in!different!stages!of!apoptosis,!
which!express!as!inactive!proenzymes!form!(procaspase)!in!cells.!The!activation!of!
any!caspases!further!activate!other!procaspases!and!initiate!a!protease!cascade!to!
amplify!the!apoptotic!signaling!pathway!and!the!proteolytic!effect!(Kumar,!2007).!
Caspases! can! be! categorized! into! three! classes:! the! initiator! caspases! the!
propagate!the!apoptotic!signal!(caspaseS2,!S8,!S9!and!S10),!effector!caspases!the!
directly!cleave!the!target!proteins!or!nucleotides! (caspaseS3,! S6!and!S7)!and!the!
inflammatory!caspases!that!are!related!to!necrosis!causing!apoptosis!(caspaseS1,!S
!
! 15!
4! and! S5)! (Cohen,! 1997;! Rai! et! al.,! 2005).! Other! minor! caspases,! for! example,!
caspaseS11,!S12,!S13!andS14,!are!identified!to!be!functional!in!specialStissueSunique!
apoptosis!caused!under!specific!stresses!(Hu!et!al.,!1998;!Kang!et!al.,!2002;!Koenig!
et!al.,!2001;!Nakagawa!et!al.,!2000).!Initiator!procaspase!can!be!activated!under!
apoptotic! signals,! while! the! activation! of! executor! procaspase! depends! on! the!
activated! initiator! to! trigger! an! internal! cleavage! event.! The! process! cleaves!
executor! caspases! separated! subunits,! following! with! the! dimerization! of! the!
isolated! subunits! and! from! the! functional! protease! to! digest! their! target!
biomolecules!in!the!execution!pathway!(Adams!&!Cory,!2002;!Shi,!2002).! !
!
The! execution! pathway! indicates! the! end! phase! of! a! caspase! cascade.! In! the!
execution!phase,!activated!executioner!caspaseS3,!S6,!and!S7!cleave!biomolecules!
including!cytokeratins,!polySADP!ribose!polymerase!(PARP)!that!is!responsible!for!
DNA!repair,!plasma!membrane!cytoskeletal!protein!and!various!nuclear!proteins!
(Slee!et!al.,!2001).!CaspaseS3!can!be!activated!by!initiator!caspaseS8,!S9!or!S10!in!
both! intrinsic! and! extrinsic! pathways! of! apoptosis! and! further! enables!
endonuclease!CAD!for!chromosomal!DNA!degradation!(Sakahira!et!al.,!1998).!An!
actinSbinding!protein!gelsolin!will!also!be!cleaved!by!activated!caspaseS3!and!cause!
extensive! destruction! on! the! cellular! cytoskeleton! and! the! intracellular!
transportation!network! (Kothakota!et!al.,!1997).!The!cellular!division!and!signal!
transduction!processes!are!thus!disrupted!directly,!and!all!cellular!functions!will!be!
ceased.! ! !
In! an! osmotic! challenge! to! euryhaline! fishes,! the! erratic! external! environment!
conditions!put!the!gill!cells!to!the!threat!of!apoptosis.!The!regulation!of!apoptosis!
is!thus!one!of!the!main!parts!to!elucidate!the!strategy!of!Japanese!eel!to!maintain!
their!cellular!functions!in!waters!with!a!wide!range!of!salinity.!
!
! 16!
4.3)+Inhibitors+of+apoptosis+(IAPs)+!
IAPs!are!one!of!the!regulators!targeting!caspases!to!regulate!apoptotic!activities!in!
both!the!intrinsic!and!extrinsic!pathways!(Deveraux!and!Reed,!1999).!To!date,!eight!
mammalian! IAP! proteins! have! been! identified! (OberoiSKhanuja! et! al.,! 2013).! In!
aquatic!animals,!IAPsSlike!genes!and!proteins!have!been!found!in!oysters!(Qu!et!al.,!
2015).! IAPs! are! also! known! as! BIR! domainScontaining! proteins! (BIRCs)! as! all!
members!of!IAPs!contain!at!least!one!Baculovirus!IAP!Repeat!(BIR)!domain.!IAPs!
genes!are!highly!conserved!from!viruses!to!mammals!(Birnbaum!et!al.,!1994;!Crook!
et! al.,! 1993).! Members! of! the! IAPs! also! show! other! structural! similarities;! for!
example,!the!reallySinterestingSnewSgene!(RING)!domain! is!present! in!the!family!
member!of!cIAP1,!cIAP2,!XIAP,!MLSIAP!and!hILP2!to!equip!the!proteins!with!an!E3!
ubiquitin!ligase!activity!for!autoSubiquitination,!crossSubiquitination!of!other!IAPs!
and!substrate!ubiquitination.!cIAP1,!cIAP2,!XIAP,!and!ILP2!also!share!a!ubiquitinS
associated!domain!(UBA)!to!promote!cell!signaling!(Husnjak!&!Dikic,!2012).! !
IAPs! can! regulate! each! other.! Nevertheless,! IAPs! can! also! regulate! different!
biological!pathways!and!components!(Cheung!et!al.,!2008).!IAPs!have!revealed!to!
be!present!in!heteromeric!complexes!(Rajalingam!et!al.,!2006).!The!heteromeric!
complex! of! two! IAPs! members,! survivin! and! XIAP,! has! shown! to! establish! a!
resistance!of!apoptosis!in!cells!(Dohi!et!al.,!2004).!Furthermore,!structural!function!
analysis!has!reported!the!BIR3!domain!on!XIAP!can!bind!directly!to!the!subunit!of!
the! caspase! initiator! caspaseS9.! The! process! inhibits! caspaseS9! activation! and!
suppresses!its!function!on!the!activation!of!the!caspase!cascade!(Srinivasula!et!al.,!
2001).! The! BIR2! domain! of! XIAP! has! also! revealed! the! highSaffinity! binding! to!
executor!caspasesS3!and!S7!and!occlude!the!binding!of!substrates!to!the!active!site!
of!the!caspases!(Chai!et!al.,!2001;!Riedl!et!al.,!2001).!With!the!functions!to!inhibit!
!
! 17!
the!activation!of!caspase!cascade!and!the!proteolytic!reaction!manufacture!by!the!
caspase!proteins,!IAPs!lie!as!one!of!the!clues!for!the!gill!cells!of!euryhaline!fishes!
to!against!apoptosis.! !
! !
!
! 18!
5.+Objectives+!
In! the! life! cycle! of! the! catadromous! Japanese! eels,! they! migrate! between!
freshwater! and! seawater.! The! substantial! change! in! water! salinity! imposes!
considerable!osmotic!stress!on!the!fishes.!As!the!fish!gills!are!in!direct!contact!with!
the!ambient!water,!acute,!and!chronic!cellular!response/acclimation!are!required!
to! maintain! the! cellular! homeostasis,! to! prevent! cell! damage.! In! the! previous!
studies,! there! are! extensive! data! on! ionSosmoregulatory! functions! of! gills! of!
Japanese!eels.!However,!the!cellular!mechanisms!against!the!apoptotic!effects!of!
osmotic!stress!have!not!been!fully!elucidated.! ! !
In!this!study,!the!primary!objectives!are!to:!
!
i)!To!characterize!the!molecular!responses!of!gill!cells!under!hypertonic!stress!by!
using!transcriptome!analysis!and!functional!annotation;!and! !
ii)!To!determine!the!effects!of!dexamethasone!on!the!cellular!viability!of!gill!cells!
upon!osmotic!challenges! !
!
! !
!
! 19!
Chapter+2+ +!
Transcriptomic+Analysis+of+Ex(Vivo+Gill+Filaments+under+Hyperosmotic+Challenge(!
2.1+Introduction+!
Most!fishes!are!stenohaline.!To!maintain!fluid!and!electrolytes!balance,!saltwater!
stenohaline! fishes!drink!ambient!water!and!eliminate!excess! salts! through!gills.! !
In!contrast,!freshwater!stenohaline!fishes!absorb!salts!from!the!ambient!water!and!
excrete!diluted!urine!(Evans,!1993).!There!is!a!small!proportion!of!fishes!known!as!
euryhaline;!those!can!tolerate!a!board!range!of!salinity!at!some!stages!of!their!life!
cycle! (Moyle! &! Cech,! 2004).! These! fishes! possess! the! ability! to! modify! the!
expression! levels! and! trafficking! of! ion! transport! in! the! polarized! cells! of! ionS
transporting! epithelial,! like! gills,! intestines,! and! kidneys! to! retain! homeostatic!
levels!of! ions!and!water!(Evans!et!al.,!2005;!Hwang!et!al.,!2011;!Tipsmark!et!al.,!
2002).! In! the! past! decades,! the! gills! of! euryhaline! fish,! Japanese! eel! (Anguilla#
japonica)! has! been! used! as! a! study! model! on! osmoregulation.! Different!
physiological! modifications! for! osmoregulatory! processes! have! been! identified!
upon! hypoS! or! hyperSosmotic! stress.! These! physiological! modifications! mainly!
involve! in! ion! transportation,! hormonal! control! and! the! expression! of! ion!
transporter!proteins!(Cao!et!al.,!2018).!The!epithelial!membrane!of!gills,!consisting!
of! pavement! cells! (PVCs)! and!mitochondria! rich! cells! (MRCs).! The! cells! express!
different! types! of! ion! transporters! during! freshwater! (FW)! or! seawater! (SW)!
acclimation.!These! transporter!proteins! include!Na/KSATPase! (NKA),!Na/K/ClScoS
transporter!(NKCC),!and!Na+/H+!exchangerS1!(NHES1)!(Tang!et!al.,!2012;!Tse!et!al.,!
2007).!Different!osmoregulatory!hormones!exert!their!effects!on!the!gills!of!both!
!
! 20!
FWS! and! SWSacclimating! Japanese! eel,! for! example,! cortisol! and! natriuretic!
peptides!(Mishina!&!Takei,!1997;!Wong!&!Chen,!2001).!Thus,!the!gill!of!Japanese!
eel! is! an! essential! model! for! the! understanding! of! different! osmoregulatory!
processes!in!fishes.! !
!
In!recent!years,!the!highSthroughput!sequencing!on!differential!gene!expression!
has!been!used!to!characterize!the!molecular!responses!of!fishes,!in!the!transition!
between!FW!and!SW!habitats!(Gu!et!al.,!2015;!Liu!et!al.,!2016).!This!methodology!
was!applied!to!the!study!of!the!gills!of! Japanese!eel! (Lai!et!al.,!2015;!Tse!et!al.,!
2013).! These! studies! revealed! differentially! expressed! genes! and! biological!
pathways!of!PVCs!and!MRCs!in!gills!of!seawater!acclimating!fish.!To!characterize!
the! molecular! responses! of! gills! in! the! absence! of! extrabranchial! factors,! this!
experimental!chapter!aimed!to!produce!a!transcriptome!profile!of!an!ex!vivo!gill!
culture.!The!ex#vivo#gill!model!can!provide!a!more!realistic!study!of! fish!gills!by!
maintaining!the!3Sdimentional!structures!of!the!gills,!including!the!arrangement!of!
the! holobranches,! hemibranches! and! the! lamellas! (Smith! et! al.,! 2018).! These!
physical!compartmental!structures!are!known!to!be!important!in!supporting!the!
gill! physiological! functions! in! directing! the!water! flow! in! order! to! enhance! the!
efficiency!for!gaseous!and!ionic!exchange!(Huges,!1966).!In!the!experimental!setup,!
gills!from!Japanese!eels!were!dissected!and!exposed!to!hypertonic!treatment!for!
4Shour!or!8Shour.!A!transcriptome!analysis!was!conducted!at!the!twoStime!points,!
which! are! equivalent! to! the! early! stage! of! the! SW! acclimation! process.! The!
differential!expressed!genes!(DEGs)!were!processed!for!functional!studies!to!reveal!
the! enriched! molecular! pathways! and! biological! processes.! The! findings! will!
provide!us!a!better!understanding!of! the!molecular!responses!of! Japanese!eel’s!
adaptation!to!the!change!of!the!environmental!osmolarity.! #
!
! 21!
Materials+and+Methods+!
i)+Animal+ +!
Japanese! eels! (Anguilla! japonica)! weighted! between! 500! to! 600! grams! were!
purchased!from!a!local!market.!The!fishes!were!kept!in!fiberglass!tanks!filled!with!
aerated!and!UV!sterilized!tap!water,!with!a!12:12!artificial!lightSdark!cycle!at!23ºC.!
The!water!was! filtered!using!carbonScanisterSrecirculating!pumps.!The!fish!were!
acclimated!for!at!least!three!weeks!before!experiments.!
!
ii)+Ex(vivo+gill+filament+culture+ +!
The! eel! was! anesthetized! with! 0.1%! ethyl! 3Saminobenzoate! methanesulfonate!
(#E10521,!SigmaSAldrich)!in!tap!water.!The!fish!was!pithed,!and!gills!were!cleared!
with! PBS! perfusion! before! dissection.! The! gill! filaments! and! divided! into! small!
pieces!of!similar!size!(1!cm!X!1!cm)!with!the!gill!arches!removed.!Filament!pieces!
were!rinsed!with!phosphateSbuffered!saline!(PBS)!(#P3813,!pH!7.7)!for!5!to!6!times!
to!remove!mucus!and!clotted!blood.!Cleaned!filament!pieces!were!cultured!in!6S
well!culture!plate!(#140675,!Thermofisher!Scientific)!with!one!piece!of!filament!in!
each! well.! Each! well! was! filled! with! 500! ul! of! Leibovitz's! LS15! Medium! (LS15,!
300mOsm/L)!(#41300039,!Gibco)!with!10%!fetal!bovine!serum!(FBS)!(#SV30106.03,!
Hyclone)!and!1%!penicillinSstreptomycin!(P/S)!(#P4333,!SigmaSAldrich).!The!culture!
was!incubated!for!at!least!an!hour!before!experimental!treatments.! ! !
!
iii)+Osmotic+stress+induction+treatment+!
A!hypertonic!medium!(600!mOsm/L)!was!prepared!with!an!addition!of!5M!NaCl!
solution! into! the! culture!medium.! The! gill! filament! culture!was! incubated!with!
!
! 22!
either!normal!L15!(300!mOsm/L)!or!modified!LS15!(600!mOsm/L).!The!sample!was!
collected!at!4S!or!8Shour!of!postSincubation.! !
! +
!
! 23!
iv)+RNA+isolation+and+quantification+ +!
Gill!filaments!were!collected.!Gill!epithelial!cells!were!scraped!and!harvested!for!
RNA! isolation.! Sample! RNA!was! extracted! using! a!mirVana!miRNA! Isolation! Kit!
(#AM1560,! Thermo! Fisher! Scientific).! Extracted! RNA! was! subjected! to! quality!
assessment!by!Agilent!2100!bioanalyzer!system!(Agilent!Technologies,!Germany).!
Samples!with!an!RNA!Integrity!Number>8!were!used!to!construct!cDNA!libraries!
for!transcriptome!sequencing.!
!
v)+Transcriptome+sequencing+ +!
cDNA!libraries!were!sequenced!by!Beijing!Genomics!Institute!(Wuhan,!China)!with!
BGISEQS500RS!sequencer!to!produce!singleSend!reads!with!a!read!length!of!150bp.!
Raw!reads!trimming!were!processed!with!SolexaQASBWA!algorithms!(Del!Fabbro!
C! et! al.,! 2013).! Trimmed! sequence! reads! were! validated! by! using! the! Kallisto!
version!0.43.0!of!the!Anguilla#japonica#transcriptome!assembly!(Bray!et!al.,!2016;!
Lai!et!al.,!2015).!Entries!were!analyzed!by!the!edgeR!package!(Robinson,!Mccarthy!
&!Smyth,!2010).!Genes!with! |log2! (fold! change:! treatment/control)! |! >!1,! log2!
count! per! million! >! 0! and! pSvalue! <! 0.05! were! considered! as! differentially!
expressed!genes.!
!
vi)+DEGs+Functional+annotation+ ++ +
Transcripts!reads!were!subjected!to!Ingenuity!Pathway!Analysis!(IPA®,!QIAGEN)!for!
the!pathway!analysis.!Pathways!with!pSvalue!<!0.05!were!considered!as!statistically!
significant.!The!transcript!reads!were!further!investigated!using!The!Database!for!
Annotation,! Visualization! and! Integrated! Discovery! (DAVID)! v6.8! for! functional!
!
! 24!
annotation! for! gene! ontology! analysis! referencing! to! the! UniProtKB/SwissSProt!
database! (Huang! et! al.,! 2009;!Michael! &!Uniport! Consortium,! 2011;! The! Gene!
Ontology!Consortium,!2017).! !
+
vii)+RealRtime+PCR+analysis+ +!
GeneSspecific! primers! were! designed! based! on! the! gene! expression! profile! of!
Japanese!eel!(Lai!at!al.,!2015)!(nucleotide!sequences!were!listed!in!table!2.1).!PCR!
was! performed! using! the! SYBR! green! PCR! master! mix! (Applied! Biosystem,!
#4347659)!in!a!StepOne!realStime!PCR!system!(Applied!Biosystem,!#4376357).!The!
mRNA!expressional!level!was!normalized!to!the!expression!of!the!housekeeping!
gene!gapdh.!
!
!
Table!2.1.)!Nucleotide!sequence!of!the!geneSspecific!primers!used!
Gene! Forward!Primer!Sequence! ! Reverse!Primer!Sequence! !
gapdh# # 5’SGCGCCAGCCAGAACATCATCS3’! 5’SGTTAAGCTCGGGGATGACCS3’!
ga45b# 5’S!ATGGAGTCTGTGGGTCAAGCS3’! 5’S!TCATCCTCGTCCTCCTCATCS3’!
tgfb3# 5’SACATCGACTTCCGACAGGACS3’! 5’S!TCAGCACTGCGTAGGTATGGS3’!
nc2a# 5’S!GAAGGACAAGAAGCAGTCGGS3’! 5’S!GCTGACCATGTGGAGGTACTGS3’!
erf1# 5’S!CGAGGTTACAAGCCAAGGTGS3’! 5’S!TCCACGCCGAAGCAATACS3’!
!
!
!
! !
!
! 25!
2.3+Results+!
i)+Transcriptome+revealed+DEGs+in+ex(vivo+gill+filament+culture+upon+hyperosmotic+stress+ +
!
The!transcriptome!data!were!collected!and!assembled!from!ex#vivo#culture#after!
the!exposure!to!600mOsm!medium!for!4!or!8!hours!(Fig.!2.1).!A!total!of!2085!DEGs!
were!identified!in!the!4!hours!of!hypertonic!stress!treatment.!There!were!890!and!
1195!upS!or!downSregulated!DEGs!respectively.!In!the!8!hours!of!the!hypertonic!
treatment,!1670!DEGs!were!identified,!with!841!DEGs!were!upregulated!and!892!
DEGs!downregulated!(Fig.!2.2).!A!further!comparison!was!made!using!the!two!DEG!
profiles!at!4!and!8!hours!for!commonly!dysregulated!genes.!A!total!of!577!common!
DEGs!were!upregulated!at!the!4S!or!8Shours!hypertonic!treatment!(Supp.!table!1).!
While!711!DEGs!were!found!commonly!downregulated!at!both!the!time!points!(Fig.!
2.3)! (Supp.! table! 2).! Two! upregulated! DEGs! candidates,! and! 2! downregulated!
candidates!were!selected!for!qPCR!validation.!The!candidates!were!chosen!by!the!
following! parameters:! 1)! the! expression! trend! of! the! candidates! should! be!
consistent!in!both!4S!and!8Shours!treatments,!and!2)!the!candidates!should!have!
at! least! 1.5SfoldSchange! in! both! timeSpoints.! 4! DEGs! candidates! were! chosen!
according!to!the!above!parameters!for!qPCR!validation.!All!qPCR!validation!results!
showed!the!same!expressional!pattern!as!the!transcriptome!data!acquired!(Fig.!
2.4).! ! ! !
! !
!
! 26!
ii)+Functional+analysis+ +!
The! common!DEGs! identified! from! the! two! timeSpoints!were! subjected! to! IPA!
pathway!analysis.!A!total!of!441!Ingenuity!Canonical!Pathways!were!identified!with!
130! enriched! pathways! that! were! statistically! significant! (Supp.! table! 3).! The!
enriched! pathways! involved! in! various! biological! functions,! including! stress!
adaptation! (e.g.,! endoplasmic! reticulum! stress! pathway),! transmembrane!
receptors! signaling! and! transportation! regulation! (e.g.,! RAN! signaling,! RAR!
activation),! apoptotic! regulation! and! DNA! damage! repairing! (p53! signaling,!
GADD45!signaling,!death!receptor!signaling)!(Fig.!2.5).! !
!
The!common!DEGs! identified! from!the!twoStime!points!were! further!compared!
with!the!UniProtKB/SwissSProt!database!by!DAVID!version!6.8!for!gene!ontology!
analysis! (Fig.! 2.6).! A! total! of! 964! common! DEGs! were! identified! as! unique!
UniProtKB! entries! through! ID! mapping.! The! analysis! was! divided! into! three!
categories:! biological! process,!molecule! functions,! and! the! cellular! component.!
90.3%! of! the! common!DEGs!were! found! responsible! for! at! least! one! enriched!
proposed! biological! process.! 119! DEGs! (12.65%)! and! 109! DEGs! (11.5%)! were!
involved! in! cellular! protein! metabolic! process! and! cellular! macromolecule!
biosynthesis!process,!respectively.!Other!identified!enriched!biological!processes!
are!mainly!related!to!protein!regulation!or!modification,!signal!transduction,!and!
metabolic!processes.!Programmed!cell!death!relating!processes!was!one!of! the!
enriched!processes.!Correlated!biological!processes!include!the!apoptotic!process!
(rank!15th,!5.1%!DEGs),!regulation!of!apoptotic!process!(rank!18/19th,!4.2%!DEGs),!
and!regulation!of!programmed!cell!death!(rank!18/19th,!4.2%!DEGs).!There!was!
86.6%!of!the!common!DEGs!were!found!to!enrich!at!least!one!specific!molecular!
!
! 27!
function,!with!266!DEGd!(28.1%)!and!222!DEGs!(23.4%)!were!recruited!for!binding!
and!protein!binding!functions!respectively.!Enrichment!of!catalytic!activities!was!
promoted! by! 122! genes! (12.9%),! ranked! the! third! most! enriched! molecule!
function.! There!were! 94.5%! of! DEGs! found! to! be! enriched! in! different! cellular!
components,!with!110!DEGs!(11.6%)!enriched!in!the!cytoplasm,!and!81!DEGs!(8.5%)!
enriched!in!the!cytosol.!Some!genes!were!associated!with!specific!compartments!
of!the!cells,!for!example,!nucleoplasm!(rank!3rd!6.9%!DEGs),!Golgi!apparatus!(rank!
7th,!2.8%!DEGs),!and!endoplasmic!reticulum!(rank!8th,!2.6%!DEGs).!
!
!
!
Fig.+2.1+A+schematic+diagram+of+the+workflow+of+the+study.+
Japanese! eel! gill! filaments! were! subjected! to! 600!mOsm/L! for! 4S! or! 8S! hours)!
treatment.!Samples!were!subjected!to!transcriptome!sequencing.!DEGs!identified!
from! both! transcriptome! data! sets! were! further! assembled! for! functional!
annotation!studies.!
Osmotic!stress!induction!600mOsm/L!
!
! 28!
!
!
Fig.+2.2+Valcano+plots+of+DEGs+identified+from+the+ex#vivo+culture+model+after+4L+
(upper)+and+8L+hours+(lower)+hypertonic+stress+induction.!
2085! DEGs! were! found! under! 4! hours! of! hypertonic! stress,! with! 890! genes!
upregulated! and! 1195! genes! downregulated.! 1670! DEGs! were! found! under! 8!
hours! of! hypertonic! treatment,! with! 841! genes! upregulated! and! 829! genes!
downregulated.!Genes!with!|log2!(fold!change:!treatment/control)|!>!1,!Slog10!qS
value!>!2!were!defined!as!DEGs!in!the!analysis.!
!
!
!
!
!
!
!
!
!
! 29!
!
Fig.+ 2.3+Venn+diagram+showed+ comparison+between+ the+DEGs+ from+4L+ and+8L+
hours+hypertonic+treatment.!
577! genes! were! commonly! upregulated! and! 771! genes! were! commonly!
downregulated.!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
! 30!
!
Fig+2.4+Transcriptome+data+validation+by+qPCR.!
Four!candidates!of!DEGs!were!picked!for!the!validation!process,!including!ga45b,!
tgfbr3,! nc2a,! and! erf1.# All! genes! show! the! same!mRNA! expressional! trend! as!
identified!in!the!transcriptome!sequencing.!
!
!
!
!
!
!
!
!
!
!
!
! 31!
!Fig.+ 2.5+ Bar+ chart+ showing+ the+ significance+ of+ the+ top+ 20+ enriched+ Ingenuity+
Canonical+Pathways.!
The!line!graph!represents!the!number!of!genes!identified!from!the!transcriptome!
study!to!the!number!of!known!gene!involved!in!the!specific!pathway.! !
!
!
!
!
!
!
!
! 32!
!
Fig.+2.6+Gene+ontology+analysis+of+common+DEGs+by+DAVID.+
Bar!charts!showing!the!top!20th!enriched!gene!ontology!(GO)!terms!in!biological!
process!(top),!molecular!function!(middle),!and!cellular!component!(down).! !
!
!
! 33!
2.4+Discussion+!
i)+Acute+osmotic+stress+induces+a+broad+set+of+dysregulated+genes+ +!
A! total! of! 1288!DEGs!were! revealed! in! transcriptome! study! to! share! the! same!
expressional!patterns!after!4S!or!8Shours!exposure!to!A!600mOsm/L!treatment,!
account!for!34.3!%!(1288/3755)!of!the!total!DEGs!identified.!The!result!expressed!
that!the! immediate!toleration!and!adaptation!of!osmotic!stress! in!Japanese!eel!
involved!a!stable!and!regular!subset!of!genes.! !
!
ii)+Acute+osmotic+stress+did+not+induce+the+expression+of+ion+transporters+!
Under! osmotic! stresses,! the! gills! of! Japanese! eel! have! been! established! as! an!
important!organ!for!the!balancing!of!fluid!and!electrolytes!between!the!ambient!
water! and! the! inner! body! environment.! The! plasticity! and! expression! of! ion!
transporters,! for!example,!Na+/K+!ATpase,!ClS!channel!CFTR!and!water!channel!
aquaporins!in!PVCs!and!MRCs!have!enable!the!transportation!of!ions!and!water!
across!the!cellular!membranes!(Maclver!et!al.,!2009;!Tang!et!al.,!2012;!Tse!et!al.,!
2006).!Thus,!the!enrichment!of!relating!pathways!and!biological!processes!were!
expected! in! gill! filaments! after! exposure! to! hyperosmotic! pressure.! However,!
common! ion! transportation! pathways! have! not! been! identified! as! an! enriched!
Ingenuity!Canonical!Pathways.!Similar!result!has!been!mentioned!in!Wong!et!al.,!
2017,!which!suggesting!that!ionic!transporter!such!as!NKCC!and!CFTR!were!not!the!
early!responsive!genes!to!hyperosmotic!stress!(Wong!et!al.,!2017).! !
In!this!study,!the!glucocorticoid!receptor!pathway!(rank!14th)!is!the!only!enriched!
ion!transporter!associated!pathway!which!is!known!to!regulate!osmoregulation.!
IN! hindsight,! cortisol! regulates! gill! fundtions! in! SW! acclimation! (Sandor! et! al.,!
!
! 34!
1984).! Cortisol! is! a! stimulating! factor! for! the! expression! of! osmotic! stress!
transcription! factor! 1! (ostf1)! in! the! gills! of! Japanese! eel! (Chow! et! al.,! 2013).!
Meanwhile,!ostf1!has!been!studied!in!various!type!of!fishes!and!were!upregulated!
in! SW!acclimation! (Tse,!2014).! Thus,! the!enrichment!of! glucocorticoid! receptor!
signaling!pathway!is!coherent!to!previous!studies!of!SW!acclimation!of!the!fish!gills!
in!Japanese!eels.! !
!
iii)+Enhanced+tgfb3(expression+evidenced+SW+acclimation+process+in+the+ex(vivo(gill+model+ +
!
To! further! validate! the! presence! SW!acclimation! process! under! the! hypertonic!
treatment,! tgfbr3# was! chosen! as! a! candidate! for! qPCR.! tgfbr3! was! highly!
upregulated!in!the!transcriptome!of!Japanese!eel!intestine!in!the!early!stage!of!SW!
acclimation! (Wong! et! al.,! 2017).# tgfbr3# is! also! one! of! the! targets! of! the! SW!
acclimation!hormone!glucocorticoid! that#plays!a! critical! role! in! inhibiting!TGFSβ!
signaling! induced! apoptosis! (Chu! et! al.,! 2011).! The! upregulated! expression! on!
tgfbr3! suggests! that! the! inhibtion! of! apoptosis! occurred! in! the! exposure! to!
hypertonicity.!Thus,!it!makes!the!study!of!cell!death!processes!and!its!regulation!
as!one!of!the!possible!focus!in!later!discussion.!
!
iv)+Osmotic+stress+showed+disruptions+to+cellular+homeostasis,+and+trigger+cell+death+responses+in+Japanese+eel+ + +
!
Although! Japanese! eels! are! known! for! their! ability! in! osmotic! stress! tolerance,!
hypertonic! stress! apparently! perturb! many! cellular! processes.! Form! the! IPA!
pathway! analysis,! the! significantly! enriched! unfolded! protein! response! (UPR)!
indicates! the! disruption! of! endoplasmic! reticulum! homeostasis,! whereas! the!
!
! 35!
unrestored!ER!homeostasis!often!leads!to!the!ER!stress!induced!cell!death!(Sano!
&!Reed,!2013).!It!comes!to!our!concern!that!a!certain!number!of!cell!death!and!
DNA! repairing! pathways! were! enriched,! including! the! p53! signaling! pathway,!
GADD45B!pathway!and!the!death!receptor!pathway.!In!the!GO!analysis,!apoptosis!
and! programmed! cell! death!were! the! top! 20! enriched! biological! processes.! To!
validate!the!result,!we!picked!gadd45b!as!a!validation!target,!as!it!is!a!DNA!damage!
marker!and!a!stress!sensor!(Schäfer,!2013).!gadd45b#was!significantly!upregulated!
in!our!transcriptome!studies!(4.13!fold!upregulated!in!4Shour!treatment,!6.93!fold!
upregulated!in!8Shour!treatment).!The!upregulation!of!gadd45!indicated!that!the!
promoted!biological!processes!of!cell!senescence,!cell!cycle!arrest,!DNA!repairing!
mechanisms!or!apoptosis!(Zumbrun!et!al.,!2009).! !
!
v)+Enriched+molecular+function+lied+clues+for+the+molecular+mechanism+that+interrupted+translation+process+or+protein+synthesis+
!
With!the!highly!enriched!unfolded!responses!and!cell!death!pathways,!this!study!
picked!two!highly!enriched!gene!involved!in!the!most!enriched!molecule!function!
for! qPCR! validation.! ! The! downregulated! eukaryotic! translation! termination!
factor!1!(etf1),!which!encode!the!protein!eRF1,!was!selected.!In!eukaryotes,!eRF1!
is!the!only!release!factor!(RF)!which!can!recognize!all!three!types!of!stop!codons.!
eRF1! functions! in! pair!with! the!GTPase! eRF3! as! a! protein! complex! to!mediate!
translation!termination!(Frolova!et!al.,!1996).!From!our!transcriptome!data,!etf1!is!
one!of!the!DEGs!with!the!most!reduced!expression!(13.83Sfold!downregulated!in!
4h!treatment,!15.89Sfold!down!regulated!in!8h!treatment).!In!yeast,!the!depletion!
of!etf1!showed!a!reduction!in!the!efficiency!of!translation!termination,!resulting!in!
errors! in!the!translation!processes!and!the!release!of!proteins!(Stansfield!et!al.,!
!
! 36!
1996).!The!significant!downregulation!of!etf1!in!the!study!might!explain!the!highly!
enriched!UPR!and!cell!death!pathways.! !
!
Another! commonly!downregulated!DEG!nc2α# is! identified! in!our! transcriptome!
data!to!be!associated!with!the!“binding”!category!(3.53Sfold!downregulated!in!4h!
treatment,!5.54Sfold!downregulated!in!8h!treatment).!The!encoded!protein!NC2α!
functions!with!NC2β!as!a!protein!complex!binding!to!the!TATA!box!(Goppelt!et!al.,!
1996).! The!NC2STATASbinding! proteinSDNA! complex! inhibits! the! recruitment! of!
transcription! factor! IIB! and! in! part! of! transcription! factor! IIA! to! repress!
transcription! (Kamada!et!al.,!2001).!The!decreased!expression!of!nc2a! can!thus!
disrupt!the!regulation!of!transcriptional!process!and!disturb!the!homeostasis!of!
cells!in!SW!acclimating!Japanese!eel.!
! !
!
! 37!
2.5+Summary++ +
In! conclusion,! osmotic! stress! has! shown! disruption! in! the! transcriptional!
regulation!in!Japanese!eel!and!evidenced!an!alteration!of!cellular!homeostasis!in!
the!early!process!of!SW!acclimation.!Although!ionic!balance!has!been!studied!as!a!
vital!process!in!osmoregulation!of!Japanese!eel,!our!study!has!shown!the!challenge!
to!retain!transcriptional!and!translational!regulation,!and!the!suppression!of!cell!
death!events!has!paved!an!early!obstacle!for!euryhaline!fishes.!
!
!
! !
!
! 38!
Chapter+3+ +!
The+AntiRapoptotic+Role+of+Dexamethasone+on+Gill+cells+upon+Osmotic+Challenge+ +!
3.1+Introduction+
+
Japanese! eels! are! euryhaline! fishes! that! can! live! in! both! fresh! and! seawater!
environments.!The!changing!environmental!salinity!often!imposes!osmotic!stress!
on!fishes!and!perturbs!their!fluid!and!electrolyte!balance.!Eventually,!it!interrupts!
cellular!homeostasis!and!threatens!the!viability!of!cells!(Shabala,!2009).!A!previous!
study!showed!hyperosmotic!stressSinduced!apoptosis!in!gill!cells!of!Mozambique!
tilapia!(Oreochromis#mossambicus)!and!impaired!the!osmoregulatory!functions!of!
the!gills!(Inokuchi!&!Kaneko,!2012).!Hashimoto!et!al.! (1998)!also!suggested!that!
apoptotic! and! necrotic! processes! were! induced! in! fish! gill! cells! when! fishes!
encountered!hypertonic! stress.!A! study!on! the!epithelioma!papulosum!cyprinid!
(EPC)!fish!cellSculture!model!showed!that!the!culture!acclimated!at!400mOsm/L!
exhibited! higher! tolerance! to! hypertonicity! (600S700mOsm/L).! ! Less! apoptosis!
was!triggered!as!compared!with!the!culture!acclimated!at!300mOsm/L!(Hashimoto!
et!al.,!1999).!The!study!suggested!that!fish!cells!can!gradually!withstand!a!higher!
osmolality,!yet!the!specific!molecular!responses!on!the!regulation!of!hypertonicityS
induced! apoptosis/necrosis! were! not! known.! With! the! hindsight! of! the!
transcriptome! study! from! the! previous! chapter,! cellular! stress! or! cell! death!
responses!were!provoked!in!the!Japanese!eel!gill!filaments!after!the!exposure!to!a!
hyperosmotic!treatment.!Cell!death!regulation!is!thus!a!vital!study!field!to!reveal!
the!survival!strategy!of!euryhaline!fishes.! ! !
!
!
! 39!
This!chapter!aimed!to!reveal!the!molecular!responses!of!apoptosis!in!Japanese!eel!
using!the!inSvitro!primary!gill!cell!and!the!exSvivo!gill!filament!culture!models.!Two!
primary! regulators,! the! (i)! hormonal! control! system! and! (ii)! the! inhibitors! of!
apoptosis!(IAPs),!were!focused!in!this!study.!Cortisol!plays!a!role!in!Japanese!eel!
during! seawater! acclimation,!with! the! induction! of! osmotic! stress! transcription!
factor! 1! (ostf1)! through! the! AktSGSK3β! pathway! (Chow! et! al.,! 2013).! Both! the!
intrinsic! and! extrinsic! apoptotic! pathways! highly! collaborated! with! the! Akt!
pathways!as!AKT!is!a!negative!regulator!of!apoptosis.!AKT!signals!inhibit!apoptotic!
processes!mediated!by! the! apoptosis! initiators!Bcl2! associated!death!promoter!
(Bad)! and! caspaseS9! to! prolong! cell! survival! (Datte! et! al.,! 1999).! Presumably,!
cortisol!may!also! regulate! the!apoptotic! responses!of! Japanese!eel! through! the!
regulation!of!caspase!activation.!Meanwhile,!IAPs!are!believed!to!be!the!clues!for!
oysters! to! survive! in! extreme! environmental! conditions! as! there! are! 48! genes!
coding!for!IAPs.! It! is!notably!more!than!the!number!of!IAPs!genes!in!humans!(8!
genes)!and!other!aquatic!animals!living!in!a!stable!range!of!salinity,!for!example,!
sea!urchins!(7!genes)!(Zhang!et!al.,!2012).!Thus,!it!makes!a!rational!prediction!that!
Japanese!eel!may!have!a! similar!mechanism! to! survive! in!waters!with!different!
salinity.!This!study!investigated!1.)!the!IAPs!expression!in!the!gills!under!hypertonic!
treatment,!2.)!the!roles!of!IAPs!in!the!regulation!of!the!apoptotic!events!in!the!gills,!
and!3.)!whether!IAPs!expression!was!regulated!by!cortisol.! !
!
!
!
!
!
!
!
! 40!
Materials+and+Methods+
!
i)+Animal++ +
Japanese! eels! (Anguilla# japonica)! weighted! between! 500! to! 600! grams! were!
purchased!from!a!local!market!and!were!kept!in!fiberglass!tanks,!filled!with!aerated!
tap!water.!Water!was!sanitized!by!UV!light!and!filtered!through!a!carbonScanisterS
recirculating!pump.!The!aquarium!was!maintained!at!23ºC!with!a!12:12!artificial!
lightSdark! cycle.! The! fish! were! acclimated! for! at! least! three! weeks! before!
experiments.!
!
ii)(In(vitro(primary+gill+cell+culture++ +
The! eel! was! anesthetized! with! 0.1%! ethyl! 3Saminobenzoate! methanesulfonate!
(MSS222)! (#E10521,! SigmaSAldrich)! in! tap! water.! Gills! were! perfused! with!
phosphateSbuffered! saline! (PBS,! pH! 7.7)! before! excision.! Gill! filaments! were!
separated! into! small! pieces! (1cm! X! 1cm)! with! the! gill! arches! removed.! The!
filaments!were!rinsed!with!PBS!for!5S6!times.!Filaments!were!then!subjected!to!
enzymatic! digestion! with! trypsin/EDTA! solution! in! PBS! (0.5%! trypsin! (#T4799,!
SigmaSAldrich),!0.53mM!EDTA!solution!(#15575S038,!Gibco))!for!20!minutes.!The!
enzymatic!digestion!was!processed!at!room!temperature!with!steady!shaking!at!
250!rpm.!The!filaments!were!subjected!to!enzymatic!digestion!twice!before!the!
collecting!of!cells.!
The!cell!suspension!was!filtered!by!a!200Ssize!mesh!(#S4145S5EA,!SigmaSAldrich)!
to!remove!the!debris!of!the!gill!filaments!and!centrifuged!at!1500!rpm!at!4ºC!for!5!
minutes.!The!cell!pellet!was!then!reSsuspended!in!iceScold!PBS!with!5%!fetal!bovine!
serum!(FBS)!(#SV30106.03,!Hyclone)!and!1%!penicillinSstreptomycin!(P/S)!(#P4333,!
!
! 41!
SigmaSAldrich).!The!cell!suspension!was!subject!to!centrifugation.!The!cell!pellet!
was!then!reSsuspended!in!Leibovitz's!LS15!Medium!(LS15)!(#41300039,!Gibco)!with!
10%! FBS,! 1%! gentamicin! (#15750S060,! Gibco),! 1%! P/S! and! 1:1000! insulin!
transferrin! selenium! (ITS)! (#11074547001,! Roche).! Cells! were! seeded! onto!
collagenScoated! plates! (Iwaki)! and! maintained! at! room! temperature! for! 20S22!
hours!before!further!experimental!procedures.!The!cells!were!washed!by!PBS!with!
1%!P/S!and!incubated!in!L15!with!1%!P/S!preceding!any!treatment.!
#
iii)+Ex(vivo(gill+filament+culture+ +!
The!eel!was!anesthetized!with!0.1%!MSS222!in!tap!water!before!the!gill!excision.!
The!gills!were!perfused!with!PBS!prior!to!isolation.!The!gill!arches!were!removed.!
The!gill! filaments!were! trimmed! into! small! pieces!of! similar! size! (1! cm!X1! cm).!
Filament!pieces!were!rinsed!with!PBS!for!5S6!times!before!the!placement!in!a!6S
well!culture!plate!(#140675,!Thermofisher!Scientific)!LS15!with!1%!P/S.! !
!
iv)+Hormonal+treatment+and+osmotic+stress+induction+treatment+!
Overnight! gill! cell! culture! proceeded! to! osmotic! stress! treatment.!A! hypertonic!
medium!(400!mOsmo/L,!500!mOsm/L,!600!mOsm/L,!700!mOsm/L!or!800!mOsm/L)!
was!prepared!with!an!addition!of!different!volumes!of!5M!NaCl!into!the!culture!
medium.!In!contrast,!hypotonic!stress!(200mOsmo/L)!was!prepared!by!diluting!the!
culture! medium! with! sterilized! milliSQ! water.! ! Dexamethasone! (DEX)! powder!
(#265005,! Calbiochem),! an! agonist! of! the! glucocorticoid! receptor! (GR),! was!
dissolved!in!dimethyl!sulfoxide!(DMSO)!(#D8418,!SigmaSAldrich)!to!make!a!10mM!
stock!solution.!Hormonal!treatments!were!introduced!into!the!culture!medium!an!
hour!prior!to!the!osmotic!stress!treatments.! !
!
! 42!
vi)+Protein+extraction+and+western+blot+ +!
For! the! in# vitro#primary! cell! culture,! cells!were! rinsed!with! PBS! and! lysed!with!
radioimmunoprecipitation!assay!(RIPA)!buffer.!For!the!ex#vivo#gill!filament!culture,!
gill! cells! were! obtained! from! the! filaments! by! scraping,! which! was! then!
homogenized! in! RIPA!buffer.! The!protein! samples!were! then! subject! to! protein!
determination!with!BioRad!DC!Protein!assay!(#5000111,!BioRad).!The!samples!(40!
µg!protein!per!lane)!were!resolved!in!a!10!%!polyacrylamide!SDS!PAGE!gel,!which!
was!then!blotted!onto!a!polyvinylidene!difluoride!(PVDF)!membrane!(#162S0177,!
Biorad).!Western!Blot!was!processed!using! a!mouse!antibody! against! fish! actin!
(1:100)!(mouse,!JLA20,!Developmental!Studies!Hybridoma!Bank)!with!horseradish!
peroxidaseSconjugated! goat! antiSmouse! antibody.! While! the! use! of! rabbit!
antibodies!against!proScaspase!3!(1:1000)!(rabbit,!#9662,!Cell!Signaling),!cleaved!
caspase!3! (1:1000)! (rabbit,!#9664,!Cell!Signaling),!PARP! (1:1000)! (rabbit,!#9532,!
Cell!Signaling),! survivin! (rabbit,!#2808,!Cell!Signaling)!and!XIAP! (1:1000)! (rabbit,!
#2045,! Cell! Signaling),! were! with! horseradish! peroxidaseSconjugated! goat! antiS
rabbit!antibody.!Protein!expression!was!visualized!with!a!specific!band!presented!
on! the! blot! after! the! addition! of! chemiluminescence! reagent! (#YIFSLFSQC0101,!
AbFrontier).! !
!
! !
!
! 43!
3.3+Result+
!
In(vitro(gill+cell+model+!
i)+Hyperosmotic+stress+reduced+the+viability+of+gill+epithelial+cells+
+
This! study!applied! the! in#vitro!primary!cell!model! to! investigate! the!early! stage!
morphological! change! of! gill! cells! caused! by! the! exposure! to! the! hypertonic!
environment.! In! the! 1Shour! 400! and! 500!mOsm/L! treatment,! the! cells! showed!
several! morphological! changes,! including! the! decline! in! cell! number,! cell!
detachment!from!the!culture!plate,!and!cell!shrinkage!(Fig.!3.1).! !
!
ii)+Hyperosmolarity+triggered+the+activation+of+apoptotic+executor+caspase+3+
+
Western!blot!was!conducted!to!test!whether!hypertonic!treatment! induced!cell!
death!in!the!cells.!The!activation!of!caspaseS3!was!observed!with!the!presence!of!
cleavedScaspase!3!(Fig.!3.2A).!The!expression!of!cleavedScaspase!3!increased!with!
the!osmolarity!in!the!range!of!400!to!600!mOsm/L!but!decreased!in!the!700!and!
800! mOsm/L! treatments.! Similar! experiments! were! repeated! using! another!
hypertonic!treatment!at!400!and!500!mOsm/L!for!two!different!time!points!(Fig.!
3.2B).! The! expression! of! cleaved! caspase! was! upregulated! in! 500! mOsm/L!
treatment!treated!cells!at!both!time!points.!
!
! !
!
! 44!
iii)+The+SW+acclimation+hormone+cortisol+reduced+the+level+of+cleaved+caspaseR3+expressions+in+SW+acclimating+gill+cells+
!
In# vitro# primary! cell! culture! was! exposed! to! either! 200! mOsm/L! hypotonic!
treatment!or!400!mOsm/L!hypertonic!treatment,!with!or!without!the!addition!of!
10uM!DEX.!In!the!hypotonic!treatment,!the!addition!of!DEX!caused!an!increase!of!
proScaspase!3!(35!kDa)!and!cleaved!caspase!3!(17!kDa)!expression.!However,!DEX!
implied! an! opposite! effect! on! the! hypertonicStreated! cells! and! significantly!
reduced!the!expression!of!proScaspase!3!and!cleaved!caspase!3! in!400!mOsm/L!
hypertonic!treatment!(Fig.!3.3).! !
!
To!further!confirm!that!DEX!can!reduce!the!expression!level!of!cleaved!caspase!3!
under! SW! acclimation,! in# vitro#primary! cell! culture!was! exposed! to! hypertonic!
treatments!at!400,!500,!or!800!mOsm/L!(Fig.!3.4).!DEX!showed!the!reduction!of!
cleaved! caspase! 3! in! all! the! 3! hyperosmotic! treatments.! Morphologically,! the!
addition!of!10uM!DEX!showed!a!protective!effect!on!cells!under!hypertonic!stress!
by!preventing!the!shrinkage!of!cells!and!retained!the!population!of!cells!(Fig.!3.5).! !
!
! 45!
!
Fig.+3.1+Cell+morphology+after+exposure+to+various+osmotic+stress+for+1+hour.+
In#vitro!primary!cell!culture!was!exposed!to!hyperosmotic!treatment!of!400!or!500!
mOsm/L.!The!cell!population!was!dropping!with!the!increasing!osmolarity.!A!sign!
of! cell! detachment! was! also! seen! in! both! 400! and! 500! mOsm/L! hypertonic!
treatment!(top).! !
! !
!
! 46!
A)! !
!B)!
!
Fig.+3.2! In#vitro#primary+gill+cell+culture+showing+cleavage+of+proLcaspase3+and+
PARP+under+hypertonic+stress.+
Gill! cells! were! exposed! to! hypertonic! stress! for! 1! hour! (A).! The! expression! of!
cleaved!caspase3!was!elevated!with!an! increase!of!osmolarity! from!400! to!600!
mOsm/L.! However,! the! expression! level! dropped! at! 700! and! 800! mOsm/L!
hyperosmotic!treatments.!Meanwhile,!the!expression!of!cleaved!PARP!increased!
between!the!range!400S700!mOsm/L!but!decreased!in!800!mOsm/L!treatments.! !
!
The!expression!of!cleaved!caspase!3!was!seen!in!both!30!min!and!1Shour!exposure!
to!hypertonic!treatment!at!400!and!500!mOsm/L!(B).!The!expression!of!cleaved!
caspase!3!was!induced!strongly!at!500!mOsm/L!treatment!at!both!time!points.! !
!
!
!
!
!
! 47!
!
!
Fig.+3.3+DEX+effect+on+cells+treated+with+osmotic+treatment.+
In#vitro#primary!cell!culture!was!exposed!to!either!200mOsm/L!hypotonic!medium!
or!400mOsm/L!hypertonic!medium!for!1!hour,!with!or!without!the!addition!of!DEX.!
In!the!osmotic!treatments!without!the!addition!of!DEX,!the!expression!of!cleaved!
caspase!3!(17kDa)!increased!in!both!hypotonic!and!hypertonic!treatment,!with!a!
stronger!expression!in!hypertonic!stress.! !
In!the!osmotic!treatments!with!the!addition!of!DEX,!the!expression!of!proScaspase!
3! and! cleaved! caspase! 3! (17kDa)! was! upregulated! in! 200! mOsm/L! hypotonic!
treatment!but!significantly!reduced!in!400!mOsm/L!hypertonic!treatment.! !
!
!
!
!
!
!
!
!
!
! 48!
!
Fig.+3.4+DEX+showed+a+reduction+in+the+expression+of+cleaved+caspase+3+in+1Lhour+
hypertonic+treatments.!
In# vitro# primary! cell! culture! was! exposed! to! 400! or! 500! mOsm/L! hypertonic!
treatment.!With!the!addition!of!10uM!DEX,!the!expression!of!cleaved!caspase!3!
(17kDa)!was!reduced!in!both!400!and!500!mOsm/L!treatments!(top).!The!effect!of!
DEX!on! inhibiting! cleaved! caspaseS3! expression! can! also! be! observed! at! a! high!
hyperosmotic!treatment!(800!mOsm/L).!
!
!
!
!
!
!
!
!
!
! 49!
!Fig.+3.5+The+effect+of+10+uM+DEX+on+gill+cells+in+hypertonicity.+ +
The!cells!shrunk!and!decreased!in!viability!under!500mOsm/L.!With!the!addition!
of!10!uM!DEX,!the!shrinkage!of!the!cells!was!not!observed.! !
!
!
! 50!
Ex(vivo+gill+filament+model+!
iv)+Ex(vivo+gill+filament+culture+model+showed+proRcaspaseR3+cleavage+and+the+expression+of+inhibitors+of+apoptosis+induced+by+osmotic+treatment+ +
+
The! ex# vivo# gill! filament! culture! was! exposed! to! hypotonic! treatment! of! 200!
mOsm/L,!or!hypertonic!treatment!of!500!or!600!mOsm/L!for!8!hours.!ProScaspase!
3! (35! kDa)! was! cleaved! into! 17! kDa! cleaved! caspaseS3! fragment! in! hypertonic!
treatments,!while! there!was! little! sign! showing! the! induction! of! proScaspase! 3!
cleavage!in!the!control!and!the!hypotonic!treatment.!
!
To!find!out!the!apoptosis!regulator,!we!profiled!the!expression!of!the!inhibitors!of!
apoptosis!under!osmotic!treatments.!Two!members!of!the!inhibitors!of!apoptosis,!
XIAP,!and!survivin,!were!found!with!antiSIAPs!antibodies!through!western!blot.!The!
expression!of!XIAP!(53!kDa)!was!observed!with!200!mOsm/L!hypotonic!treatment,!
while!the!expression!of!survivin!was!seen!expressed!in!hypertonic!treatments.!The!
expression!was!slightly!increased!in!600!mOsm/L!treatments!(Fig.!3.6).! !
!
v)+Dexamethasone+reduced+caspaseR3+cleavage+and+induced+the+expression+of+XIAP+and+survivin+in+ex+vivo+gill+filament(model+under+hypertonic+treatment+ +
+
Ex# vivo! gill! filament! culture! was! exposed! to! either! 200mOsm/L! hypotonic!
treatment,! 500! mOsm/L! hypertonic! treatment,! or! 500! mOsm/L! hypertonic!
treatment!with!10!uM!DEX!(fig.!3.7).!Hypertonic!treatment!strongly!induced!the!
cleavage!of!caspase!3!in!the!500!mOsm/L!hypertonic!treatment.!In!contrast,!cells!
exposed! to!500!mOsm/L!hypertonic! treatment!with! the!addition!of!10!uM!DEX!
!
! 51!
showed!much!a!lower!expression!of!cleaved!caspase!3.!Simultaneously,!DEX!also!
upregulated! the! IAPs! expression! of! XIAP! and! survivin! in! the! 500! mOsm/L!
hypertonic!treatment.! !
!
!
!
Fig.+3.6+Western+blot+of+ex#vivo+gill+filament+culture+in+osmotic+treatment+for+8+
hours.+
ProScaspase!3!(35!kDa)!was!cleaved!into!the!cleaved!caspase!3!(17!kDa)!fragment.!
The!expressional!level!of!cleaved!caspase!3!increased!in!hyperosmotic!treatment!
at!500!and!600!mOsm/L!but!reduced!in!the!hypotonic!treatment!of!200mOsm/L.!
The!expression!of!apoptosis!inhibitor!XIAP!was!induced!by!200!mOsm/L!hypotonic!
treatment!but!not!in!hypertonic!treatment.!The!other!apoptosis!inhibitor,!survivin,!
gained! an! uprising! expression! with! the! increasing! osmolarity! in! hypertonic!
treatment!of!500!and!600!mOsm/L,!but!a!very!limiting!expression!in!200!mOsm/L!
hypotonic!treatment.! !
!
! !
!
! 52!
!Fig.+ 3.7+Western+ blot+ of+ex# vivo+ gill+ filament+ culture+ after+ 8+ hours+ of+ osmotic+
challenge+and+dexamethasone+treatment.!
Hyperosmotic! treatment! of! 500! mOsm/L! induced! the! expression! of! cleaved!
caspase!3.!The!expressional! level!was!significantly! reduced!with! the!addition!of!
10uM!DEX.!The!level!of!XIAP!was!enhanced!by!hypoosmolarity!at!200!mOsm/L!and!
only!in!500!mOsm/L!hypertonic!treatment!with!the!addition!of!DEX.!The!other!IAPs!
member,! survivin,! was! also! upregulated! by! the! addition! of! DEX! in! hypertonic!
treatment!of!500mOsm/L.! !
! !
!
! 53!
3.4+Discussion+
!
In!the!previous!chapter,!apoptoticSrelating!responses!were!revealed! in!the!gene!
expression! level! through! transcriptome!study.!To!understand! the!morphological!
change!and!the!postStranscriptional/translational!adaptation!of!the!fish!gill!under!
osmotic!stresses,!we!performed!osmotic!treatments!on! in#vivo#epithelial!gill!cell!
and!the!ex#vivo!gill!filament!model!protein!in!this!chapter.!
!
i)+Hypertonicity+activates+proRcaspaseR3+cleavage+and+apoptosis+ +
+
In! this! study,! we! observed! that! hyperosmotic! stress! led! to! cell! shrinkage! and!
decreased!the!population!of! living!cells.!Simultaneously,!the!apoptosis!executor,!
proScaspase!3,!was!found!to!be!cleaved!to! its!active!form,!cleavedScaspase!3,! in!
hypertonic! treatments! from! 400! mOsm/L! to! 600! mOsm/L.! As! restricting! DNA!
repairing!is!one!of!the!key!features!of!apoptosis,!the!increased!expression!levels!of!
the!cleavage!of!the!DNA!damage!repairing!protein,!PARP,!further!supported!the!
indication! of! apoptosis! (Soldani! &! Scovassi,! 2002).! Yet,! the! expression! of! the!
cleaved!caspase!3!dropped!in!700S800mOsm/L!treatment.!These!result!matches!to!
a!previous!study!showing!that!apoptosis!was!induced!in!epithelioma!papulosum!
cyprini!(EPC)!at!400S600mOsm/kg,!while!necrosis!was!induced!at!higher!osmolarity!
(Hisashi!et!al.,!1998).! !
!
These! results! have! shown! that! hyperosmotic! stress! can! induce! apoptosis!
responses! in! the! gills! of! Japanese! eels.! Indeed,! the! induction! of! procaspase! 3!
cleavage!and!activation!of!apoptosis!by!hyperosmolarity!were!reported!in!rat!and!
Xenopus! models! (Ben! et! al.,! 2015;! Niswander! &! Dokas,! 2007).! Our! findings!
!
! 54!
suggested!that!caspase!3!dependent!apoptosis! in!Japanese!eels!was!induced!by!
hypertonicity.!In!euryhaline!fish,!additional!regulatory!mechanisms!should!be!onS
board!to!prevent!apoptosis!during!seawater!acclimation.! ! !
!
ii)+Dexamethasone+diminished+the+threat+of+apoptosis+in+gill+cells+under+hyperosmotic+treatment+
!
Dexamethasone,!one!of!the!glucocorticoid!receptor!agonists!that!can!mimic!the!
effect!of!cortisol!hormone,!was!reported!to!induce!the!expression!of!ostf1#through!
the! AktSGSK3β! pathway! in! Japanese! eel! (Chow! at! al.,! 2013).! Although! an!
upregulated! level! of! serum! cortisol! has! shown! to! be! essential! for! fishes,! for!
example,! groupers,! to! survive! in! a! hypertonic! environment,! the! molecular!
responses!of!cortisol!on!hypertonicity!induced!apoptosis!is!still!not!known!(Tahir!
et!al.,!2018).!
!
In! our! study,! the! addition! of! DEX! significantly! reduced! the! expression! of! proS
caspase!3!in!Japanese!eel!gill!cells!at!hypertonic!treatment!but!not!in!hypotonic!
treatment.!This!effect!was!also!noted!at!an!extreme!of!hyperosmotic!treatment!at!
800!mOsm/L,!which!was!very!close!to!the!average!osmolarity!of!seawater!(1000!
mOsm/L).!As!one!of!the!main!executors!of!apoptosis,!the!downregulated!level!of!
caspase!3!proteins!greatly!eliminates!the!threat!of!apoptosis!in!the!gill!cells!caused!
by!the!hypertonic!environmental!stress.! !
!
!
! !
!
! 55!
iii)+Expression+of+inhibitors+of+apoptosis+were+induced+by+osmotic+pressure+ +
!
To! further! investigate! the! regulation! of! the! activation! of! caspase! 3! in! gill! cells!
under! hyperosmotic! pressure,!we! adapted! the! ex# vivo! gill! filament!model! and!
projected!the!gill! filaments!to!different!hypertonic!treatments.!Similar!to!the! in#
vitro# gill! cell! model,! there! was! an! increase! of! the! active! cleavedScaspaseS3!
fragments!(17!kDa)!at!the!hypertonic!treatment!of!500S600mOsm/L!but!not!in!the!
hypotonic!treatment!of!200mOsm/L.!In!addition,!the!expression!of!the!inhibitor!of!
apoptosis!(IAPs)!was!firstly!observed!in!the!gill!of!Japanese!eel.! !
!
IAPs!are!known!to!interact!with!caspases!proteins!to!regulate!apoptotic!activities!
in!both!mammals!and!drosophila!(Deveraux!et!al.,!1997;!Meier!et!al.,!2000).!XIAP,!
a!member!of!the!IAPs,!was!detectable!in!gill!filaments!at!hypotonic!treatment!but!
not!at!the!hypertonic!treatment.!XIAP!has!shown!clear!inhibition!on!the!activation!
of!caspases,! including!the!intrinsic!apoptosis!specific! initiator!caspase!9!and!the!
apoptosis!executors!caspase!3!or!caspase!7!through!the!binding!at!the!different!
domain!to!inhibit!their!activation!(Deveraux!et!al.,!1997;!Shiozaki!et!al,!2003).!The!
working!mechanism!of!XIAP! thus!makes! it!possible!postStranslational!apoptosis!
regulator!in!Japanese!eel.! !
!
Simultaneously,!another!IAPs!member,!survivin,!was!increasingly!expressed!with!
high!osmolarity! (fig.! 6).! Survivin!has!been! studied!as!an!essential!promotor! for!
tumorigenesis!as!it!inhibits!the!activity!of!caspase!3!to!prevent!apoptosis!(Li!et!al.,!
2017).!Although!the!domains!on!survivin!do!not!show!direct!binding!with!caspases,!
!
! 56!
it! forms! complexes! with! other! IAPs! and! functions! as! a! caspase! inhibitory! unit!
(Srinivasula!&!Ashwell,!2008).! !
!
The!expression!of! IAPs!has!paved!a!hint! for! the!postStranslational! regulation!of!
apoptotic!events!in!Japanese!eel.!It!lies!an!efficient!mechanism!to!maintain!cellular!
viability!by!adjourning!the!activation!of!both!apoptosis!initiators!(e.g.!caspase!9)!
and! apoptosis! executors! (e.g.! caspase! 3).! Thus,! a! further! investigation! on! how!
Japanese!eel!uses! IAPs! to! limit!apoptosis! induced!by!hypertonic!stress! is!worth!
conducting.!
!
iv)+Dexamethasone+prompts+the+expression+of+both+XIAP+and+survivin+in+the+ex(vivo(gill+filament+culture+under+hypertonic+treatment+ +
+
With! the! expression! of! IAPs! and! inhibitory! effect! of! DEX! on! the! activation! of!
caspase! 3,! IAPs! inhibition! and! hormonal! control! are! suggested! to! have! an!
important!role!in!apoptotic!regulation!of!the!gill!cell!of!Japanese!eel.!To!validate!
whether!these!factors!would!affect!the!apoptotic!activities!of!the!gill!cells!exposing!
to!hypertonic!treatment,!we!exposed!ex#vivo!gill!filament!culture!in!a!500!mOsm/L!
hypertonic!treatment!with!the!addition!of!DEX.! !
!
The!presence!of!DEX!induced!the!expression!of!XIAP!and!survivin!in!the!gill!under!
in!hypertonic!treatment.!Meanwhile,!the!level!of!cleaved!caspase!3!was!dropped!
significantly.! With! the! known! function! as! the! caspase! proteins! inhibitors,! the!
upregulation!of!XIAP!and!survivin!are!suggested!to!suppress!hypertonicity!induced!
apoptosis!in!Japanese!eels!undergoing!seawater!acclimation.!XIAP!inhibits!caspase!
3! by! preventing! caspase! 3! from!binding!with! its! target! substrates! (Ridel! et! al.,!
!
! 57!
2001).!While!Dohi!et!al.!(2004)!reported!that!survivin!works!as!a!complex!with!XIAP.!
As!DEX!can! induce!both!XIAP!and!survivin!expressions! in!gill!cells!at!hypertonic!
treatment,! two! possible! mechanisms! are! suggested! to! regulate! caspase! 3!
activation!1.)!DEX!induces!XIAP!and!directly!inhibit!caspase!3!cleavage!and!2.)!the!
induced!XIAP!bind!with!survivin!to! form!an! IAPSIAP!complex!to! inhibit!caspases!
activities.!
! !
!
! 58!
3.5+Summary+ +
!
The! in#vitro#primary!gill!cell!culture!and!ex#vivo#gill!filament!culture!have!shown!
that!the!cleavage!of!caspase!3!was!induced!by!hypertonic!treatment.!A!decrease!
of! the! cell! population! was! also! observed! under! hypertonic! treatment.! In!
conclusion,!both!molecular!responses!and!morphological!observation!suggested!
that!apoptosis!was!induced!when!the!cells!were!exposed!to!hyperosmotic!stress.!
This!study!has!demonstrated!that!DEX,!an!agonist!of!the!glucocorticoid!receptor,!
mimicking!the!effect!of!cortisol!hormonal,!has!the!ability!to!hinder!the!activation!
of!caspase!3!in!Japanese!eel!under!hyperosmotic!pressure.!The!findings!
suggested!cortisol!hormone!is!responsible!for!the!induction!of!the!expression!of!
XIAP!and!survivin!in!gill!cells!under!hypertonic!treatment.!The!inhibitory!effects!
of!these!IAPs!on!the!activation!of!caspase!executors!may!be!the!possible!strategy!
that!Japanese!eel!adopted!as!a!postStranslational!apoptosis!regulator!while!they!
are!in!the!process!of!seawater!acclimation.!The!process!lies!critically!to!maintain!
the!stability!of!the!cellular!epithelial!layer!and!the!normal!functioning!of!the!gills.!
! !
!
! 59!
Appendix(!Supplementary!Table!1.!Commonly!upregulated!DEG!from!transcriptome!analysis!Transcript*Read*ID* Uniprot*ID* Unigene*name*from*DAVID* * Gene*Symbol*c95280_g3_i2! O15294! OElinked!NEacetylglucosamine!(GlcNAc)!transferase(OGT)! OGT1!c87719_g1_i5! Q9H930! SP140!nuclear!body!protein!like(SP140L)! LY10L!c82578_g1_i1! Q96T92! INSM!transcriptional!repressor!2(INSM2)! INSM2!c84714_g1_i4! P50616! transducer!of!ERBB2,!1(TOB1)! TOB1!c77130_g1_i1! Q99615! DnaJ!heat!shock!protein!family!(Hsp40)!member!C7(DNAJC7)! DNJC7!c84760_g1_i5! Q9Y5R5! doublesex!and!mabE3!related!transcription!factor!2(DMRT2)! DMRT2!c54095_g1_i1! Q16787! laminin!subunit!alpha!3(LAMA3)! LAMA3!c91261_g4_i3! Q8WYK2! Jun!dimerization!protein!2(JDP2)! JDP2!c91261_g4_i4! Q78E65! Jun!dimerization!protein!2(Jdp2)! JDP2!c113279_g1_i1! Q8BH83! ankyrin!repeat!domain!9(Ankrd9)! ANKR9!c72226_g1_i1! P11939! FBJ!murine!osteosarcoma!viral!oncogene!homolog(FOS)! FOS!c112739_g1_i1! P19632! phosducin(PDC)! PHOS!c57853_g1_i1! Q704V6! toll!like!receptor!6(TLR6)! TLR6!c58896_g1_i3! Q9QW30! notch!2(Notch2)! NOTC2!c64677_g1_i1! Q8AXV6! hesErelated!family!bHLH!transcription!factor!with!YRPW!motif!1(hey1)! HEY1!c95642_g1_i4! P23276! Kell!blood!group,!metalloEendopeptidase(KEL)! KELL!
!
! 60!
c86014_g1_i1! Q6NW59! activating!transcription!factor!4a(atf4a)! ATF4!c62223_g1_i1! Q96HZ4! hes!family!bHLH!transcription!factor!6(HES6)! HES6!c16071_g1_i1! P38029! alphaE1Eantitrypsin(SPI2)! A1AT2!c78619_g1_i1! Q6IRB2! hes!family!bHLH!transcription!factor!1!L!homeolog(hes1.L)! HES1A!c93366_g2_i1! Q8JG38! fibroblast!growth!factor!receptor!2(fgfr2)! FGFR2!c91099_g2_i1! Q04666! hes!family!bHLH!transcription!factor!1(Hes1)! HES1!c99424_g1_i5! Q8N328! ERCC!excision!repair!6,!chromatin!remodeling!factor(ERCC6)! PGBD3!c80261_g1_i1! A5D8S8! hexamethylene!bisEacetamide!inducible!1(hexim1)! HEXIM!c96254_g2_i5! O76080! zinc!finger!AN1Etype!containing!5(ZFAND5)! ZFAN5!c79143_g1_i1! P27469! G0/G1!switch!2(G0S2)! G0S2!c83742_g1_i1! O75293! growth!arrest!and!DNA!damage!inducible!beta(GADD45B)! GA45B!c82891_g1_i1! Q8AVU4! hes!family!bHLH!transcription!factor!1!S!homeolog(hes1.S)! HES1B!c91055_g1_i4! P26632! early!growth!response!1(egr1)! EGR1!c95837_g2_i3! P50616! transducer!of!ERBB2,!1(TOB1)! TOB1!c91099_g2_i3! Q04666! hes!family!bHLH!transcription!factor!1(Hes1)! HES1!c86650_g1_i1! P28562! dual!specificity!phosphatase!1(DUSP1)! DUS1!c66748_g1_i1! Q9Z0J7! growth!differentiation!factor!15(Gdf15)! GDF15!c47838_g1_i1! Q5RED5! TSC22!domain!family!member!3(TSC22D3)! T22D3!c78099_g3_i1! Q9BTL4! immediate!early!response!2(IER2)! IER2!c37161_g1_i1! P07359! glycoprotein!Ib!platelet!alpha!subunit(GP1BA)! GP1BA!c90876_g1_i4! O43474! Kruppel!like!factor!4(KLF4)! KLF4!
!
! 61!
c73426_g1_i1! Q1LWL8!vEmyc!avian!myelocytomatosis!viral!oncogene!lung!carcinoma!derived!homolog!b(myclb)! MCL1B!
c61887_g1_i1! Q8IYE1! coiledEcoil!domain!containing!13(CCDC13)! CCD13!c84714_g1_i1! P50616! transducer!of!ERBB2,!1(TOB1)! TOB1!c81867_g1_i2! Q6P788! activating!transcription!factor!5(Atf5)! ATF5!c18111_g1_i1! Q8CJ69! BMPEbinding!endothelial!regulator(Bmper)! BMPER!c86882_g1_i3! Q9UJG1! motile!sperm!domain!containing!1(MOSPD1)! MSPD1!c91278_g4_i1! Q04799! flavin!containing!monooxygenase!5(FMO5)! FMO5!c84714_g1_i3! P50616! transducer!of!ERBB2,!1(TOB1)! TOB1!c99189_g1_i3! Q63028! adducin!1(Add1)! ADDA!c81829_g1_i1! Q3TYX8! RUN!and!FYVE!domain!containing!4(Rufy4)! RUFY4!c98007_g1_i2! Q08CI4! cyclin!YElike!1(ccnyl1)! CCYL1!c86086_g2_i1! P41134! inhibitor!of!DNA!binding!1,!HLH!protein(ID1)! ID1!c81705_g1_i1! Q6NTY6! early!growth!response!1!S!homeolog(egr1.S)! EGR1B!c83780_g1_i1! Q8K4C0! flavin!containing!monooxygenase!5(Fmo5)! FMO5!c85737_g1_i1! Q13410! butyrophilin!subfamily!1!member!A1(BTN1A1)! BT1A1!c52283_g1_i2! Q5SW45! Meckel!syndrome,!type!1(Mks1)! MKS1!c94460_g1_i3! A0AUS0! WD!repeat,!sterile!alpha!motif!and!UEbox!domain!containing!1(wdsub1)! WSDU1!c45394_g1_i1! Q5ZIW1! chromosome!10!open!reading!frame!2(C10orf2)! PEO1!c79670_g1_i1! Q9BY76! angiopoietin!like!4(ANGPTL4)! ANGL4!c128440_g1_i1! Q767K9! protein!phosphatase!1!regulatory!subunit!10(PPP1R10)! PP1RA!
!
! 62!
c95037_g1_i1! Q13237! protein!kinase,!cGMPEdependent,!type!II(PRKG2)! KGP2!
c100802_g1_i1! A3KMR8!vEmaf!avian!musculoaponeurotic!fibrosarcoma!oncogene!homolog!Aa(mafaa)! MAFA!
c21398_g1_i1! Q05718! insulin!like!growth!factor!binding!protein!6(IGFBP6)! IBP6!c90948_g2_i1! P49796! regulator!of!GEprotein!signaling!3(RGS3)! RGS3!c58041_g1_i1! Q9PTH3! insulinElike!growth!factor!binding!protein!2a(igfbp2a)! IBP2A!c63696_g1_i1! Q6UFS5! zinc!finger!protein!503(znf503)! ZN503!c72988_g1_i1! Q6MFZ5! tripartite!motifEcontaining!39(Trim39)! TRI39!c91055_g1_i1! P26632! early!growth!response!1(egr1)! EGR1!c89364_g2_i1! P46628! lysophosphatidic!acid!receptor!1(LPAR1)! LPAR1!c81373_g1_i1! Q28626! syntrophin!alpha!1(SNTA1)! SNTA1!c92429_g1_i2! P70338! growth!factor!independent!1(Gfi1)! GFI1!c81864_g2_i2! Q13277! syntaxin!3(STX3)! STX3!c127656_g1_i1! P18892! butyrophilin,!subfamily!1,!member!A1(BTN1A1)! BT1A1!c89515_g2_i2! Q5NCC3! tripartite!motifEcontaining!41(Trim41)! TRI41!c75444_g1_i1! Q9Z1P3! BCL2!family!apoptosis!regulator(Mcl1)! MCL1!c93366_g2_i4! Q8JG38! fibroblast!growth!factor!receptor!2(fgfr2)! FGFR2!c156270_g1_i1! Q5F3L3! family!with!sequence!similarity!234!member!B(FAM234B)! K1467!c98636_g1_i3! P25940! collagen!type!V!alpha!3!chain(COL5A3)! CO5A3!c90948_g2_i2! P49796! regulator!of!GEprotein!signaling!3(RGS3)! RGS3!c83739_g1_i1! O35569! neuregulin!2(Nrg2)! NRG2!
!
! 63!
c84069_g1_i1! P29279! connective!tissue!growth!factor(CTGF)! CTGF!c87316_g1_i1! Q2KIX1! growth!arrest!and!DNA!damage!inducible!gamma(GADD45G)! GA45G!c73104_g1_i1! Q9H336! cysteine!rich!secretory!protein!LCCL!domain!containing!1(CRISPLD1)! CRLD1!c72904_g1_i1! O94769! extracellular!matrix!protein!2(ECM2)! ECM2!c52381_g1_i1! Q8VD50! DNAEdamageEinducible!transcript!4Elike!2(Ddit4l2)! DDT4L!c74717_g1_i1! O75293! growth!arrest!and!DNA!damage!inducible!beta(GADD45B)! GA45B!
c8422_g1_i1! P27607!prostaglandinEendoperoxide!synthase!2!(prostaglandin!G/H!synthase!and!cyclooxygenase)(PTGS2)! PGH2!
c88500_g1_i1! P78543! BTG!antiEproliferation!factor!2(BTG2)! BTG2!c69988_g1_i1! Q6PC60! histone!2,!H2,!like(hist2h2l)! H2B3!c98074_g1_i5! Q5S007! leucine!rich!repeat!kinase!2(LRRK2)! LRRK2!c94591_g1_i2! P0CI65! nephronophthisis!3(nphp3)! NPHP3!c95214_g1_i4! Q17RC7! exocyst!complex!component!3!like!4(EXOC3L4)! EX3L4!c74717_g1_i2! O75293! growth!arrest!and!DNA!damage!inducible!beta(GADD45B)! GA45B!
c72227_g1_i1! P27607!prostaglandinEendoperoxide!synthase!2!(prostaglandin!G/H!synthase!and!cyclooxygenase)(PTGS2)! PGH2!
c72790_g1_i1! Q7Z5L7! podocan(PODN)! PODN!c91261_g4_i1! Q8WYK2! Jun!dimerization!protein!2(JDP2)! JDP2!c65218_g1_i1! Q5DWN0! growth!factor!independent!1!transcriptional!repressor(GFI1)! GFI1!c92104_g2_i1! A1L253! family!with!sequence!similarity!149,!member!B1(fam149b1)! F149B!c86798_g1_i2! Q8C1B2! TCDDEinducible!poly(ADPEribose)!polymerase(Tiparp)! PARPT!
!
! 64!
c99203_g1_i2! Q9Y6T7! diacylglycerol!kinase!beta(DGKB)! DGKB!c82449_g1_i1! Q5RDU4! poly(ADPEribose)!polymerase!family!member!6(PARP6)! PARP6!c89742_g3_i3! Q8BN82! solute!carrier!family!17!(anion/sugar!transporter),!member!5(Slc17a5)! S17A5!c90456_g1_i5! Q96S94! cyclin!L2(CCNL2)! CCNL2!c96852_g1_i4! Q6NZ18! KIAA0907!protein(kiaa0907)! K0907!c73107_g1_i1! Q99JW5! epithelial!cell!adhesion!molecule(Epcam)! EPCAM!c97493_g2_i2! Q52KG5! kinesin!family!member!26A(Kif26a)! KI26A!
c91079_g1_i1! Q7TM99!solute!carrier!family!16!(monocarboxylic!acid!transporters),!member!9(Slc16a9)! MOT9!
c85077_g1_i1! O00560! syndecan!binding!protein(SDCBP)! SDCB1!c85205_g2_i2! Q99JB8! protein!kinase!C!and!casein!kinase!substrate!in!neurons!3(Pacsin3)! PACN3!c77872_g1_i2! A8WGB1! collagen!and!calcium!binding!EGF!domains!1(ccbe1)! CCBE1!c80330_g1_i1! Q90X67! suppressor!of!cytokine!signaling!3(SOCS3)! SOCS3!c73307_g2_i1! Q9JLA3! UDPEglucose!glycoprotein!glucosyltransferase!1(Uggt1)! UGGG1!c86464_g2_i5! O94868! FCH!and!double!SH3!domains!2(FCHSD2)! FCSD2!c86854_g1_i1! O75600! glycine!CEacetyltransferase(GCAT)! KBL!
c72227_g1_i2! P27607!prostaglandinEendoperoxide!synthase!2!(prostaglandin!G/H!synthase!and!cyclooxygenase)(PTGS2)! PGH2!
c90456_g1_i9! Q96S94! cyclin!L2(CCNL2)! CCNL2!c95764_g1_i5! Q9D4P0! ADPEribosylation!factorElike!5B(Arl5b)! ARL5B!c80774_g1_i1! P24522! growth!arrest!and!DNA!damage!inducible!alpha(GADD45A)! GA45A!
!
! 65!
c79362_g1_i1! Q9NXJ0! membrane!spanning!4Edomains!A12(MS4A12)! M4A12!
c89157_g3_i1! P30664!minichromosome!maintenance!complex!component!4!S!homeolog(mcm4.S)! MCM4B!
c70385_g1_i1! Q9Z1E3!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!B!cells!inhibitor,!alpha(Nfkbia)! IKBA!
c92468_g1_i1! Q0VC30! DNA!polymerase!gamma!2,!accessory!subunit(POLG2)! DPOG2!c111355_g1_i1! Q8K368! Fanconi!anemia,!complementation!group!I(Fanci)! FANCI!c76861_g1_i3! Q5R1W4! tubulin,!alpha!1b(TUBA1B)! TBA1B!c80112_g1_i1! O43474! Kruppel!like!factor!4(KLF4)! KLF4!c98455_g1_i2! P39447! tight!junction!protein!1(Tjp1)! ZO1!c101754_g1_i1! Q6ZTW0! tubulin!polyglutamylase!complex!subunit!1(TPGS1)! TPGS1!c87949_g1_i2! A0JMK8! zgc:153929(zgc:153929)! BICR2!c64471_g1_i1! Q9EPQ8! transcription!factor!20(Tcf20)! TCF20!c86086_g3_i1! P41134! inhibitor!of!DNA!binding!1,!HLH!protein(ID1)! ID1!c23208_g1_i1! Q9WTN5! two!pore!segment!channel!1(Tpcn1)! TPC1!c87522_g1_i2! P97503! NK3!homeobox!2(Nkx3E2)! NKX32!c78599_g1_i1! Q3T0C9! synaptojanin!2!binding!protein(SYNJ2BP)! SYJ2B!c78088_g1_i2! Q8CFJ7! solute!carrier!family!25,!member!45(Slc25a45)! S2545!c80112_g1_i2! O43474! Kruppel!like!factor!4(KLF4)! KLF4!c58906_g1_i1! Q9HCE3! zinc!finger!protein!532(ZNF532)! ZN532!c90865_g1_i1! Q4R6P7! sestrin!1(SESN1)! SESN1!
!
! 66!
c9705_g1_i1! Q5SPB6! ChaC,!cation!transport!regulator!homolog!1!(E.!coli)(chac1)! CHAC1!c85505_g1_i1! Q6NYT3! immediate!early!response!5Elike(ier5l)! IER5L!c78713_g2_i1! Q13304! G!proteinEcoupled!receptor!17(GPR17)! GPR17!c99060_g1_i5! P50053! ketohexokinase(KHK)! KHK!c92001_g1_i1! P10820! perforin!1!(pore!forming!protein)(Prf1)! PERF!c75273_g1_i2! Q5ZJA4! ARP5!actinErelated!protein!5!homolog!(yeast)(ACTR5)! ARP5!c91261_g4_i2! Q8WYK2! Jun!dimerization!protein!2(JDP2)! JDP2!c89515_g2_i1! Q5NCC3! tripartite!motifEcontaining!41(Trim41)! TRI41!c64680_g1_i1! P22844! H1!histone!family!member!0!S!homeolog(h1f0.S)! H10B!c87761_g1_i1! Q9QZK5! HtrA!serine!peptidase!1(Htra1)! HTRA1!c51370_g2_i1! Q7TNC6! kinesin!family!member!26B(Kif26b)! KI26B!c49038_g1_i1! P98082! DAB2,!clathrin!adaptor!protein(DAB2)! DAB2!c83331_g1_i1! P19336! cysteine!rich!angiogenic!inducer!61(CYR61)! CYR61!c73264_g1_i1! Q7ZU80! limb!and!neural!patterns!a(lnpa)! LNPA!c20923_g1_i1! Q9JHE6! hairy!and!enhancer!of!split!6(Hes6)! HES6!c79148_g1_i1! P23508! mutated!in!colorectal!cancers(MCC)! CRCM!c83727_g2_i1! Q8AVH7! EGFElikeEdomain,!multiple!6!S!homeolog(egfl6.S)! EGFL6!c87134_g1_i1! Q6DGN0! RERG/RASElike!a(rergla)! RERGL!c90036_g2_i5! Q14031! collagen!type!IV!alpha!6!chain(COL4A6)! CO4A6!c99103_g1_i1! Q9NYU2! UDPEglucose!glycoprotein!glucosyltransferase!1(UGGT1)! UGGG1!c23102_g1_i1! Q99P25! translinEassociated!factor!X!(Tsnax)!interacting!protein!1(Tsnaxip1)! TXIP1!
!
! 67!
c96105_g3_i5! Q9P2D6! family!with!sequence!similarity!135!member!A(FAM135A)! F135A!c90028_g1_i2! Q6P1B1! XEprolyl!aminopeptidase!(aminopeptidase!P)!1,!soluble(Xpnpep1)! XPP1!c86014_g2_i2! Q6NW59! activating!transcription!factor!4a(atf4a)! ATF4!c47035_g1_i1! Q6EJB7! SRY!(sex!determining!region!Y)Ebox!3(sox3)! SOX3!c82035_g1_i1! Q60793! KruppelElike!factor!4!(gut)(Klf4)! KLF4!c43392_g1_i1! Q91VC4! plasmalemma!vesicle!associated!protein(Plvap)! PLVAP!c94719_g3_i1! Q8CIV7! ovo!like!zinc!finger!2(Ovol2)! OVOL2!c89580_g1_i3! Q63ZY3! KN!motif!and!ankyrin!repeat!domains!2(KANK2)! KANK2!c86086_g3_i2! P41134! inhibitor!of!DNA!binding!1,!HLH!protein(ID1)! ID1!c69844_g1_i1! Q9UPQ7! PDZ!domain!containing!ring!finger!3(PDZRN3)! PZRN3!c78194_g1_i1! P17950! immediate!early!response!2(Ier2)! IER2!c92971_g2_i2! P56545! CEterminal!binding!protein!2(CTBP2)! CTBP2!c78676_g1_i1! Q02858! endothelialEspecific!receptor!tyrosine!kinase(Tek)! TIE2!c64923_g1_i1! Q9Z265! checkpoint!kinase!2(Chek2)! CHK2!c75736_g1_i1! P18519! nerve!growth!factor!receptor(NGFR)! TNR16!c70341_g1_i1! Q69ZS0! PDZ!domain!containing!RING!finger!3(Pdzrn3)! PZRN3!c77368_g1_i1! Q9IAT6! deltaC(dlc)! DLLC!c63181_g1_i1! P13051! uracil!DNA!glycosylase(UNG)! UNG!c94634_g1_i1! Q5RCC1! engulfment!and!cell!motility!2(ELMO2)! ELMO2!c92778_g1_i3! Q5HYA8! transmembrane!protein!67(TMEM67)! MKS3!c77441_g1_i1! P07093! serpin!family!E!member!2(SERPINE2)! GDN!
!
! 68!
c82937_g1_i1! Q969Q1! tripartite!motif!containing!63(TRIM63)! TRI63!c99639_g2_i1! Q9NR80! Rho!guanine!nucleotide!exchange!factor!4(ARHGEF4)! ARHG4!c92235_g1_i2! Q810I1! tripartite!motifEcontaining!50(Trim50)! TRI50!c96865_g1_i2! Q14562! DEAHEbox!helicase!8(DHX8)! DHX8!c88286_g1_i1! Q12982! BCL2!interacting!protein!2(BNIP2)! BNIP2!c98949_g1_i3! Q7T037! ring!finger!protein,!LIM!domain!interacting!S!homeolog(rlim.S)! RF12B!c57794_g1_i1! Q66H56! TELO2!interacting!protein!2(Tti2)! TTI2!c85677_g1_i3! Q6PFM4! limb!and!neural!patterns!b(lnpb)! LNPB!c93312_g2_i4! B5DF89! cullin!3(Cul3)! CUL3!c95881_g1_i3! Q9WVG6! coactivatorEassociated!arginine!methyltransferase!1(Carm1)! CARM1!c76973_g1_i1! Q8C9B9! death!inducerEobliterator!1(Dido1)! DIDO1!c89742_g3_i1! Q9MZD1! solute!carrier!family!17!member!5(SLC17A5)! S17A5!c89881_g1_i1! Q9JI03! collagen!type!V!alpha!1!chain(Col5a1)! CO5A1!c94550_g1_i4! P20909! collagen!type!XI!alpha!1!chain(Col11a1)! COBA1!c74024_g1_i1! Q9NQT8! kinesin!family!member!13B(KIF13B)! KI13B!c90442_g1_i1! Q13202! dual!specificity!phosphatase!8(DUSP8)! DUS8!c91278_g2_i1! Q8K4C0! flavin!containing!monooxygenase!5(Fmo5)! FMO5!c93752_g2_i1! Q66PG1! glycosyltransferaseElike!1b(gyltl1b)! LARG2!c80464_g1_i1! Q9BWV1! BOC!cell!adhesion!associated,!oncogene!regulated(BOC)! BOC!c90818_g1_i7! Q5ZLK4! globoside!alphaE1,3ENEacetylgalactosaminyltransferase!1(GBGT1)! GBGT1!c87328_g1_i1! Q5R5C5! NADPH!oxidase!4(NOX4)! NOX4!
!
! 69!
c69388_g1_i1! Q5ZJA4! ARP5!actinErelated!protein!5!homolog!(yeast)(ACTR5)! ARP5!c92907_g4_i2! Q0VC81! adenosine!A3!receptor(ADORA3)! AA3R!c92058_g3_i1! Q99PE9! ADPEribosylation!factorElike!4D(Arl4d)! ARL4D!c69868_g1_i1! Q5MD89! fmsErelated!tyrosine!kinase!4(flt4)! VGFR3!c93153_g5_i1! O14595! CTD!small!phosphatase!2(CTDSP2)! CTDS2!c33444_g1_i1! P47794! cyclin!E1(ccne1)! CCNE1!c77449_g1_i1! O76074! phosphodiesterase!5A(PDE5A)! PDE5A!c82052_g1_i1! Q13609! deoxyribonuclease!1!like!3(DNASE1L3)! DNSL3!c47547_g1_i1! Q68ED7! CREB!regulated!transcription!coactivator!1(Crtc1)! CRTC1!c89465_g2_i3! Q1JPZ7! PRP39!preEmRNA!processing!factor!39!homolog!(yeast)(prpf39)! PRP39!c99881_g1_i1! Q9H1H9! kinesin!family!member!13A(KIF13A)! KI13A!
c92603_g1_i1! Q76KF0!sema!domain,!transmembrane!domain!(TM),!and!cytoplasmic!domain,!(semaphorin)!6D(Sema6d)! SEM6D!
c99312_g1_i3! Q70EK8! ubiquitin!specific!peptidase!53(USP53)! UBP53!c78366_g1_i1! Q8NI32! LY6/PLAUR!domain!containing!6B(LYPD6B)! LPD6B!c84271_g1_i1! Q58G59! kinesin!family!member!7(kif7)! KIF7!c92574_g1_i1! Q8IZJ3! C3!and!PZP!like,!alphaE2Emacroglobulin!domain!containing!8(CPAMD8)! CPMD8!c79188_g1_i1! P15882! chimerin!1(CHN1)! CHIN!c93340_g2_i1! Q03112! MDS1!and!EVI1!complex!locus(MECOM)! EVI1!c83154_g1_i1! Q2KJ51! angiopoietin!like!4(ANGPTL4)! ANGL4!c88556_g1_i1! O75096! LDL!receptor!related!protein!4(LRP4)! LRP4!
!
! 70!
c87372_g1_i2! P55212! caspase!6(CASP6)! CASP6!c43216_g1_i1! Q9Y2G4! ankyrin!repeat!domain!6(ANKRD6)! ANKR6!c81152_g1_i1! Q12955! ankyrin!3(ANK3)! ANK3!c91807_g1_i2! Q9CZV8! FEbox!and!leucineErich!repeat!protein!20(Fbxl20)! FXL20!c91338_g3_i2! Q9NQX4! myosin!VC(MYO5C)! MYO5C!c82260_g1_i2! Q4R372! FEbox!protein!25(FBXO25)! FBX25!c65469_g1_i1! P55268! laminin!subunit!beta!2(LAMB2)! LAMB2!c65506_g1_i1! Q9UBI9! hdc!homolog,!cell!cycle!regulator(HECA)! HDC!c79074_g1_i1! Q5R7A7! serum/glucocorticoid!regulated!kinase!family!member!3(SGK3)! SGK3!c98823_g1_i3! Q90X49! coiledEcoil!domain!containing!80(ccdc80)! CCD80!c81586_g1_i1! Q5ZKK5! outer!dense!fiber!of!sperm!tails!2(ODF2)! ODFP2!c98432_g1_i2! Q5ZM86! coiledEcoil!domain!containing!50(CCDC50)! CCD50!c88606_g1_i1! A2BGD5! calcium!binding!and!coiledEcoil!domain!1a(calcoco1a)! CACO1!c50405_g3_i1! Q96M63! coiledEcoil!domain!containing!114(CCDC114)! CC114!c93836_g1_i5! P16056! met!protoEoncogene(Met)! MET!c91575_g2_i2! Q9IA88! saltEinducible!kinase!1(SIK1)! SIK2!c68502_g2_i1! Q1JPY8! paraspeckle!component!1(pspc1)! PSPC1!c91278_g1_i2! Q04799! flavin!containing!monooxygenase!5(FMO5)! FMO5!c77861_g1_i2! Q16589! cyclin!G2(CCNG2)! CCNG2!c93522_g3_i4! Q13275! semaphorin!3F(SEMA3F)! SEM3F!c95691_g1_i4! Q9NS68! TNF!receptor!superfamily!member!19(TNFRSF19)! TNR19!
!
! 71!
c171887_g1_i1! P70121! zinc!fingers!and!homeoboxes!1(Zhx1)! ZHX1!
c70876_g1_i1! Q9W686!sema!domain,!immunoglobulin!domain!(Ig),!short!basic!domain,!secreted,!(semaphorin)!3Ab(sema3ab)! SE3AB!
c96997_g2_i3! P78504! jagged!1(JAG1)! JAG1!c86705_g1_i1! Q8NCT3! KIAA0895(KIAA0895)! K0895!c77897_g1_i3! O96017! checkpoint!kinase!2(CHEK2)! CHK2!c93549_g3_i4! Q96QF0! RAB3A!interacting!protein(RAB3IP)! RAB3I!c86993_g1_i2! P30404! peptidylprolyl!isomerase!F(PPIF)! PPIF!c85905_g1_i1! Q8BJ37! tyrosylEDNA!phosphodiesterase!1(Tdp1)! TYDP1!c96203_g1_i3! Q14678! KN!motif!and!ankyrin!repeat!domains!1(KANK1)! KANK1!c38255_g1_i1! A2AL36! centriolin(Cntrl)! CNTRL!c72264_g1_i1! Q9NRP7! serine/threonine!kinase!36(STK36)! STK36!c79931_g1_i1! O13046! WD!repeat!and!HMGEbox!DNA!binding!protein!1!L!homeolog(wdhd1.L)! WDHD1!c63280_g1_i1! A1A5X5! family!with!sequence!similarity!132,!member!A(fam132a)! F132A!c86866_g1_i2! Q8N0U4! family!with!sequence!similarity!185!member!A(FAM185A)! F185A!c87166_g2_i2! O70258! sarcoglycan,!epsilon(Sgce)! SGCE!c65137_g1_i1! Q8BPP0! zinc!finger!protein!46(Zfp46)! ZN436!c82970_g1_i1! O70220! forkhead!box!Q1(Foxq1)! FOXQ1!c80261_g2_i1! A5D8S8! hexamethylene!bisEacetamide!inducible!1(hexim1)! HEXIM!c94444_g4_i3! P23471! protein!tyrosine!phosphatase,!receptor!type!Z1(PTPRZ1)! PTPRZ!c65609_g1_i1! Q9BXJ5! C1q!and!tumor!necrosis!factor!related!protein!2(C1QTNF2)! C1QT2!
!
! 72!
c73417_g1_i1! Q2KIN4! hes!related!family!bHLH!transcription!factor!with!YRPW!motif!1(HEY1)! HEY1!c99501_g2_i2! Q28044! adrenoceptor!beta!2(ADRB2)! ADRB2!c90396_g2_i1! P81122! insulin!receptor!substrate!2(Irs2)! IRS2!c99185_g1_i4! P30415! natural!killer!tumor!recognition!sequence(Nktr)! NKTR!c72413_g1_i1! Q5R7A7! serum/glucocorticoid!regulated!kinase!family!member!3(SGK3)! SGK3!c97240_g1_i1! P70541! eukaryotic!translation!initiation!factor!2B,!subunit!3!gamma(Eif2b3)! EI2BG!c83618_g1_i1! A7YE96! fleer(flr)! TT30A!c92792_g1_i1! Q9W7C5! heparin!binding!EGF!like!growth!factor(HBEGF)! HBEGF!c97443_g4_i6! Q99569! plakophilin!4(PKP4)! PKP4!c70464_g1_i1! Q7ZXJ7! chemokine!(CEXEC!motif)!receptor!4!S!homeolog(cxcr4.S)! CXR4B!c88846_g1_i2! Q28691! prostaglandin!E!receptor!4(PTGER4)! PE2R4!c72571_g1_i1! Q9R1Q8! transgelin!3(Tagln3)! TAGL3!c70500_g1_i1! Q6DFB7! POC5!centriolar!protein!L!homeolog(poc5.L)! POC5!c70653_g1_i2! Q9NS91! RAD18,!E3!ubiquitin!protein!ligase(RAD18)! RAD18!c97018_g3_i4! Q17RW2! collagen!type!XXIV!alpha!1!chain(COL24A1)! COOA1!c89765_g1_i1! Q64487! protein!tyrosine!phosphatase,!receptor!type,!D(Ptprd)! PTPRD!c84387_g1_i1! Q5SZK8! FRAS1!related!extracellular!matrix!protein!2(FREM2)! FREM2!c59016_g1_i2! Q7ZUC7! prostaglandin!E!synthase!2Elike(ptgesl)! PGES2!c75672_g1_i1! Q9CXC9! ets!variant!5(Etv5)! ETV5!c99158_g1_i1! Q61292! laminin,!beta!2(Lamb2)! LAMB2!c70677_g2_i1! Q5R8L2! BMI1!protoEoncogene,!polycomb!ring!finger(BMI1)! BMI1!
!
! 73!
c78380_g1_i1! Q8IYD8! Fanconi!anemia!complementation!group!M(FANCM)! FANCM!c87323_g1_i1! Q6P0R8! shootin!1(shtn1)! SHOT1!c47711_g1_i1! Q9UL03! integrator!complex!subunit!6(INTS6)! INT6!c72748_g1_i2! Q3ZBG9! phospholipid!scramblase!1(PLSCR1)! PLS2!c89654_g1_i3! F1MJM0! zinc!finger!protein!326(ZNF326)! ZN326!c91103_g2_i1! A2A6A1! G!patch!domain!containing!8(Gpatch8)! GPTC8!c56216_g1_i1! Q9UJT0! tubulin!epsilon!1(TUBE1)! TBE!c90114_g3_i1! Q1LVC2! jumonji,!AT!rich!interactive!domain!2b(jarid2b)! JARD2!c68502_g1_i1! Q1JPY8! paraspeckle!component!1(pspc1)! PSPC1!c73950_g1_i1! Q7Z7A1! centriolin(CNTRL)! CNTRL!c50169_g1_i1! Q5VU97! cache!domain!containing!1(CACHD1)! CAHD1!c90604_g1_i1! O60573! eukaryotic!translation!initiation!factor!4E!family!member!2(EIF4E2)! IF4E2!c87738_g1_i1! Q5T7N3! KN!motif!and!ankyrin!repeat!domains!4(KANK4)! KANK4!c71273_g2_i1! Q5PRC0! cholesterol!25Ehydroxylase(ch25h)! CH25H!c95324_g2_i2! Q99KG3! RNA!binding!motif!protein!10(Rbm10)! RBM10!c97630_g3_i1! Q811U4! mitofusin!1(Mfn1)! MFN1!c95222_g1_i4! Q15678! protein!tyrosine!phosphatase,!nonEreceptor!type!14(PTPN14)! PTN14!c76930_g4_i1! Q8R3B7! bromodomain!containing!8(Brd8)! BRD8!c95218_g1_i2! Q61245! collagen,!type!XI,!alpha!1(Col11a1)! COBA1!
c81787_g1_i1! Q1LWL8!vEmyc!avian!myelocytomatosis!viral!oncogene!lung!carcinoma!derived!homolog!b(myclb)! MCL1B!
!
! 74!
c90242_g1_i3! Q2QLA2! cortactin!binding!protein!2(CTTNBP2)! CTTB2!c88555_g1_i2! Q8R4Y8! rotatin(Rttn)! RTTN!c92704_g1_i1! Q62231! sine!oculisErelated!homeobox!1(Six1)! SIX1!c91232_g1_i4! Q9Y6R4! mitogenEactivated!protein!kinase!kinase!kinase!4(MAP3K4)! M3K4!c88143_g1_i1! Q6PFL8! thymocyte!nuclear!protein!1(thyn1)! THYN1!c94991_g3_i1! Q28628! AEkinase!anchoring!protein!9(AKAP9)! AKAP9!c83430_g1_i1! Q96RT8! tubulin!gamma!complex!associated!protein!5(TUBGCP5)! GCP5!c82966_g1_i1! Q8TDP1! ribonuclease!H2!subunit!C(RNASEH2C)! RNH2C!c95779_g2_i2! Q9H0H5! Rac!GTPase!activating!protein!1(RACGAP1)! RGAP1!c92971_g2_i4! P56545! CEterminal!binding!protein!2(CTBP2)! CTBP2!c76397_g1_i2! Q6P9A2! polypeptide!NEacetylgalactosaminyltransferase!18(GALNT18)! GLT18!c91611_g1_i5! Q14103! heterogeneous!nuclear!ribonucleoprotein!D(HNRNPD)! HNRPD!c71431_g1_i1! Q96JK4! HHIP!like!1(HHIPL1)! HIPL1!c86973_g2_i1! Q9WUV0! origin!recognition!complex,!subunit!5(Orc5)! ORC5!c89219_g1_i4! Q7ZVX5! receptor!accessory!protein!3b(reep3b)! REEP3!c92017_g1_i2! P0CM60! betaEcatenin(CNA03500)! VAC8!c99255_g1_i2! Q8R146! acylpeptide!hydrolase(Apeh)! APEH!c81516_g1_i1! Q5VU97! cache!domain!containing!1(CACHD1)! CAHD1!
c96178_g1_i3! Q7ZUP0!acidic!(leucineErich)!nuclear!phosphoprotein!32!family,!member!A(anp32a)! AN32A!
c92627_g2_i3! Q9Y6K8! adenylate!kinase!5(AK5)! KAD5!
!
! 75!
c71138_g2_i2! Q6UXI9! nephronectin(NPNT)! NPNT!c92033_g2_i5! P33896! interferon!(alpha!and!beta)!receptor!1(Ifnar1)! INAR1!c85199_g1_i3! Q68G74! LIM!homeobox!8(LHX8)! LHX8!c80997_g1_i1! Q9N281! collagen!type!XVII!alpha!1!chain(COL17A1)! COHA1!c92042_g2_i1! Q5ZHN3! WD!repeat!domain,!phosphoinositide!interacting!2(WIPI2)! WIPI2!c98663_g1_i6! O73622! Primordial!germ!cellEassociated!transcript!protein!L!homeolog(pgat.L)! PAT!c98285_g1_i3! Q4KMQ2! anoctamin!6(ANO6)! ANO6!c78586_g2_i1! Q90ZE4! presenilin!2(psen2)! PSN2!c89061_g1_i2! Q9ULE0! WWC!family!member!3(WWC3)! WWC3!c84780_g1_i1! Q5ZKK5! outer!dense!fiber!of!sperm!tails!2(ODF2)! ODFP2!c99315_g1_i3! Q3UHU5! microtubule!crosslinking!factor!1(Mtcl1)! SOGA2!c90323_g2_i1! Q02337! 3Ehydroxybutyrate!dehydrogenase,!type!1(BDH1)! BDH!c97400_g1_i1! Q7T2H2! fibroblast!growth!factor!receptorElike!1(FGFRL1)! FGRL1!c83108_g1_i4! Q6PFR5! transformer!2!alpha!homolog!(Drosophila)(Tra2a)! TRA2A!c68435_g1_i1! Q16787! laminin!subunit!alpha!3(LAMA3)! LAMA3!
c94422_g1_i1! Q8K1B9!UDPENEacetylEalphaEDEgalactosamine:polypeptide!NEacetylgalactosaminyltransferase!18(Galnt18)! GLT18!
c88030_g1_i1! O75496! geminin,!DNA!replication!inhibitor(GMNN)! GEMI!c64944_g1_i1! Q60843! KruppelElike!factor!2!(lung)(Klf2)! KLF2!c96151_g5_i1! Q5SP90! SMEK!homolog!1,!suppressor!of!mek1!(Dictyostelium)(smek1)! PP4R3!c98433_g6_i1! Q7JJ13! bromodomain!containing!2(Brd2)! BRD2!
!
! 76!
c70523_g1_i1! Q92522! H1!histone!family!member!X(H1FX)! H1X!c86871_g1_i3! Q9WUE4! nitrogen!permease!regulatorElike!2(Nprl2)! NPRL2!c83279_g1_i1! Q6AXJ9! cyclinEdependent!kinaseElike!1!(CDC2Erelated!kinase)(cdkl1)! CDKL1!c75695_g1_i1! O93533! gap!junction!protein,!beta!6,!30kDa(GJB6)! CXB6!c60488_g1_i1! Q8IZJ3! C3!and!PZP!like,!alphaE2Emacroglobulin!domain!containing!8(CPAMD8)! CPMD8!c74721_g2_i1! P05121! serpin!family!E!member!1(SERPINE1)! PAI1!c93017_g1_i1! Q6PEM6! GRAM!domain!containing!3(Gramd3)! GRAM3!c90634_g1_i1! Q06AS9! ephrin!A1(EFNA1)! EFNA1!c90218_g2_i6! O14672! ADAM!metallopeptidase!domain!10(ADAM10)! ADA10!c93013_g1_i1! Q9HA64! fructosamine!3!kinase!related!protein(FN3KRP)! KT3K!c97521_g1_i7! Q9R045! angiopoietinElike!2(Angptl2)! ANGL2!c99248_g1_i2! Q8QGQ8! period!circadian!clock!2(PER2)! PER2!c88608_g2_i1! O93484! collagen,!type!I,!alpha!2(col1a2)! CO1A2!c63228_g1_i2! Q16819! meprin!A!subunit!alpha(MEP1A)! MEP1A!c91393_g1_i1! Q9WUH4! four!and!a!half!LIM!domains!1(Fhl1)! FHL1!
c86994_g1_i6! Q92622!RUN!and!cysteine!rich!domain!containing!beclin!1!interacting!protein(RUBCN)! RUBIC!
c94871_g2_i6! Q99JZ7! ERBB!receptor!feedback!inhibitor!1(Errfi1)! ERRFI!c78508_g1_i1! Q9D8U4! C1q!and!tumor!necrosis!factor!related!protein!2(C1qtnf2)! C1QT2!c91278_g3_i2! Q8K4C0! flavin!containing!monooxygenase!5(Fmo5)! FMO5!c86942_g1_i1! P98198! ATPase!phospholipid!transporting!8B2(ATP8B2)! AT8B2!
!
! 77!
c85205_g2_i4! A7MBI0! protein!kinase!C!and!casein!kinase!substrate!in!neurons!1(PACSIN1)! PACN1!c95311_g2_i4! Q9H930! SP140!nuclear!body!protein!like(SP140L)! LY10L!c98275_g1_i1! Q3U5C8! Rho!guanine!nucleotide!exchange!factor!(GEF)!16(Arhgef16)! ARHGG!c78101_g1_i1! Q06831! SRY!(sex!determining!region!Y)Ebox!4(Sox4)! SOX4!c65475_g1_i1! Q96RG2! PAS!domain!containing!serine/threonine!kinase(PASK)! PASK!c73797_g1_i1! Q90WI4! matrixEremodelling!associated!8(MXRA8)! MXRA8!c90595_g1_i1! A5D7H2! striatin!3(STRN3)! STRN3!c98727_g2_i1! Q99683! mitogenEactivated!protein!kinase!kinase!kinase!5(MAP3K5)! M3K5!c59414_g1_i1! Q6NV32! prothymosin,!alpha!a(ptmaa)! PTMAA!c98777_g1_i7! O95544! NAD!kinase(NADK)! NADK!c97765_g1_i3! Q8VHQ9! acylECoA!thioesterase!11(Acot11)! ACO11!c64096_g2_i2! A7YT82! NEmyristoyltransferase!2(nmt2)! NMT2!c95848_g1_i2! Q7Z7A1! centriolin(CNTRL)! CNTRL!
c85284_g2_i1! Q9D2Y9!ELOVL!family!member!7,!elongation!of!long!chain!fatty!acids!(yeast)(Elovl7)! ELOV7!
c83733_g1_i1! Q0P4A4! NEacetyltransferase!14!(GCN5Erelated,!putative)(nat14)! NAT14!c87755_g1_i1! Q5F3L1! ribosomal!protein!S6!kinase,!90kDa,!polypeptide!5(RPS6KA5)! KS6A5!c97762_g1_i1! Q86VV8! rotatin(RTTN)! RTTN!c82027_g3_i1! A9JRB3! HtrA!serine!peptidase!1b(htra1b)! HTR1B!c83009_g1_i1! Q1RLQ5! family!with!sequence!similarity!69,!member!Aa(fam69aa)! FA69A!c90712_g1_i1! A0PJR5! enoyl!CoA!hydratase!domain!containing!3(echdc3)! ECHD3!
!
! 78!
c90030_g2_i1! Q5U4F6! WD!repeat!domain!34(Wdr34)! WDR34!c80329_g1_i1! Q9D915! RIKEN!cDNA!1810011O10!gene(1810011O10Rik)! CH004!c96694_g1_i9! Q86U86! polybromo!1(PBRM1)! PB1!c95470_g1_i3! Q14202! zinc!finger!MYMEtype!containing!3(ZMYM3)! ZMYM3!c93874_g1_i2! Q6DFF5! SRYEbox!9!L!homeolog(sox9.L)! SOX9B!c96302_g2_i2! P49756! RNA!binding!motif!protein!25(RBM25)! RBM25!c90564_g1_i1! A0AUS0! WD!repeat,!sterile!alpha!motif!and!UEbox!domain!containing!1(wdsub1)! WSDU1!c25026_g1_i1! Q28832! low!density!lipoprotein!receptor(LDLR)! LDLR!c76042_g1_i1! P25094! peripheral!myelin!protein!22(Pmp22)! PMP22!c98341_g1_i3! Q90610! neogenin!1(NEO1)! NEO1!c59553_g1_i1! Q90Y54! jagged!1b(jag1b)! JAG1B!c98275_g1_i4! Q3U5C8! Rho!guanine!nucleotide!exchange!factor!(GEF)!16(Arhgef16)! ARHGG!c74642_g1_i1! P61129! zinc!finger!CCCHEtype!containing!6(ZC3H6)! ZC3H6!c68143_g1_i1! Q16820! meprin!A!subunit!beta(MEP1B)! MEP1B!c93214_g3_i2! A1A4S6! Rho!GTPase!activating!protein!10(ARHGAP10)! RHG10!c90209_g1_i2! Q8BP78! FRA10AC1!homolog!(human)(Fra10ac1)! F10C1!c94323_g2_i2! P98198! ATPase!phospholipid!transporting!8B2(ATP8B2)! AT8B2!c92819_g1_i2! Q7ZVC2! clusterin!associated!protein!1(cluap1)! CLUA1!c80262_g1_i1! Q9WUT7! chemokine!(CEC!motif)!receptor!9(Ccr9)! CCR9!c81175_g1_i3! Q9WVR6! solute!carrier!family!7!member!8(Slc7a8)! LAT2!c85958_g1_i2! Q90977! E2F!transcription!factor!1(E2F1)! E2F1!
!
! 79!
c54634_g1_i2! P49879! interferon,!alpha!1(IFNA1)! IFNA1!c81647_g1_i2! Q5KR49! tropomyosin!1!(alpha)(TPM1)! TPM1!c79761_g2_i1! O60245! protocadherin!7(PCDH7)! PCDH7!c99292_g1_i7! Q9D4J7! PHD!finger!protein!6(Phf6)! PHF6!c86597_g1_i2! F1RAX8! coenzyme!Q6!monooxygenase(coq6)! COQ6!c84907_g1_i6! Q6ZU80! centrosomal!protein!128(CEP128)! CE128!c87787_g1_i1! Q9R012! poloElike!kinase!2(Plk2)! PLK2!c76078_g1_i2! Q9Y238! deleted!in!lung!and!esophageal!cancer!1(DLEC1)! DLEC1!c96694_g1_i2! Q8BSQ9! polybromo!1(Pbrm1)! PB1!c96003_g1_i1! Q8IUF1! COBW!domain!containing!2(CBWD2)! CBWD2!
c94739_g1_i2! B2ZFP3!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!aElike!1(smarcal1)! SMAL1!
c99126_g1_i4! Q8BHC7! rhomboid!domain!containing!1(Rhbdd1)! RHBL4!
c72362_g1_i1! Q3UES3!tankyrase,!TRF1Einteracting!ankyrinErelated!ADPEribose!polymerase!2(Tnks2)! TNKS2!
c94322_g1_i1! Q8BYN5! fibronectin!type!III!and!SPRY!domain!containing!1Elike(Fsd1l)! FSD1L!c92856_g1_i1! Q9Y5Q8! general!transcription!factor!IIIC!subunit!5(GTF3C5)! TF3C5!c80046_g1_i1! Q9JJP6! tumor!protein!p63(Tp63)! P63!c69725_g2_i1! Q5R7X2! U2!snRNP!associated!SURP!domain!containing(U2SURP)! SR140!c75973_g4_i1! A1L1V4! lysyl!oxidaseElike!2b(loxl2b)! LOL2B!c79381_g1_i1! Q8BW74! hepatic!leukemia!factor(Hlf)! HLF!
!
! 80!
c85148_g1_i2! A7Z019!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!a,!member!4(SMARCA4)! SMCA4!
c70677_g1_i1! Q5R8L2! BMI1!protoEoncogene,!polycomb!ring!finger(BMI1)! BMI1!c67487_g1_i1! Q9UEY8! adducin!3(ADD3)! ADDG!c98579_g1_i2! A3KPN8! tetratricopeptide!repeat!domain!38(ttc38)! TTC38!c92468_g1_i2! Q9UHN1! DNA!polymerase!gamma!2,!accessory!subunit(POLG2)! DPOG2!c91251_g1_i2! Q8VCD7! lysine!(K)Especific!demethylase!4C(Kdm4c)! KDM4C!c79552_g1_i6! Q9EQJ0! two!pore!channel!1(Tpcn1)! TPC1!c94204_g1_i1! Q5SZK8! FRAS1!related!extracellular!matrix!protein!2(FREM2)! FREM2!c88779_g3_i2! O75626! PR/SET!domain!1(PRDM1)! PRDM1!c82027_g1_i1! A9JRB3! HtrA!serine!peptidase!1b(htra1b)! HTR1B!c68566_g1_i1! Q9H2K2! tankyrase!2(TNKS2)! TNKS2!c84831_g1_i1! P97478! demethylEQ!7(Coq7)! COQ7!c99779_g1_i3! Q9Y219! jagged!2(JAG2)! JAG2!c81660_g1_i1! Q5F363! jumonji!and!ATErich!interaction!domain!containing!2(JARID2)! JARD2!c99227_g2_i2! O54747! DNA!polymerase!delta!1,!catalytic!subunit(Pold1)! DPOD1!c98682_g1_i1! Q14667! KIAA0100(KIAA0100)! K0100!c98452_g1_i3! Q69ZN7! myoferlin(Myof)! MYOF!
c87929_g1_i1! A2CEQ0!solute!carrier!family!25!(mitochondrial!carrier;!phosphate!carrier),!member!25b(slc25a25b)! SCM2B!
!
! 81!
c73598_g1_i2! Q7ZXB1!minichromosome!maintenance!complex!component!7!L!homeolog(mcm7.L)! MCM7B!
c82623_g2_i1! Q7SYD5! SEC31!homolog!A,!COPII!coat!complex!component(sec31a)! SC31A!c63645_g1_i1! Q9Y4E5! zinc!finger!protein!451(ZNF451)! ZN451!c87490_g2_i3! Q9TUM3! signal!transducer!and!activator!of!transcription!5B(STAT5B)! STA5B!c95168_g1_i1! A1L1V4! lysyl!oxidaseElike!2b(loxl2b)! LOL2B!c86964_g1_i2! Q3UQ28! peroxidasin(Pxdn)! PXDN!c78586_g2_i2! Q90ZE4! presenilin!2(psen2)! PSN2!c96223_g4_i1! Q5R737! L3MBTL2!polycomb!repressive!complex!1!subunit(L3MBTL2)! LMBL2!c97015_g1_i1! P53355! death!associated!protein!kinase!1(DAPK1)! DAPK1!c90000_g1_i1! P46531! notch!1(NOTCH1)! NOTC1!c73311_g1_i1! Q4JIJ3! 5EmethyltetrahydrofolateEhomocysteine!methyltransferase(MTR)! METH!c97354_g1_i1! Q5H8C1! FRAS1!related!extracellular!matrix!1(FREM1)! FREM1!c89776_g1_i1! Q5M7R9! grainyheadElike!transcription!factor!2(grhl2)! GRHL2!c87545_g2_i1! P05997! collagen!type!V!alpha!2!chain(COL5A2)! CO5A2!c97630_g2_i4! Q8R4Z9! mitofusin!1(Mfn1)! MFN1!c98128_g1_i1! P18163! acylECoA!synthetase!longEchain!family!member!1(Acsl1)! ACSL1!c90262_g1_i1! O43439! CBFA2/RUNX1!translocation!partner!2(CBFA2T2)! MTG8R!c55730_g1_i1! Q00322! CCAAT/enhancer!binding!protein!(C/EBP),!delta(Cebpd)! CEBPD!c79988_g1_i1! Q0VF22! coiledEcoil!domain!containing!138(Ccdc138)! CC138!c86721_g1_i2! Q9H4B4! polo!like!kinase!3(PLK3)! PLK3!
!
! 82!
c79538_g1_i1! Q864U1! BRCA1,!DNA!repair!associated(BRCA1)! BRCA1!c98622_g1_i1! Q8NFZ0! FEbox!protein,!helicase,!18(FBXO18)! FBX18!c86259_g1_i1! O09117! synaptophysinElike!protein(Sypl)! SYPL1!c86666_g1_i1! O15440! ATP!binding!cassette!subfamily!C!member!5(ABCC5)! MRP5!c97853_g2_i1! Q6AZF8! high!mobility!group!20A!L!homeolog(hmg20a.L)! HM20A!c85884_g2_i1! Q6NWE1! PHD!finger!protein!10(phf10)! PHF10!c81504_g1_i1! Q501Z5! GTP!binding!protein!3(gtpbp3)! GTPB3!c97225_g1_i1! Q7L5Y6! deEetiolated!homolog!1!(Arabidopsis)(DET1)! DET1!c66187_g3_i1! Q05826! CCAAT/enhancer!binding!protein!(C/EBP),!beta(CEBPB)! CEBPB!c50124_g1_i1! Q567Y6! intraflagellar!transport!22!homolog!(Chlamydomonas)(ift22)! RABL5!c87905_g1_i1! Q9CZ52! anthrax!toxin!receptor!1(Antxr1)! ANTR1!c91853_g1_i1! Q90ZL2! LanC!antibiotic!synthetase!component!CElike!1!(bacterial)(lancl1)! LANC1!c91251_g1_i3! Q8VCD7! lysine!(K)Especific!demethylase!4C(Kdm4c)! KDM4C!c71883_g1_i1! Q12873! chromodomain!helicase!DNA!binding!protein!3(CHD3)! CHD3!c99339_g2_i1! Q6UFS5! zinc!finger!protein!503(znf503)! ZN503!c38593_g2_i1! Q7ZVS9! vEmyc!avian!myelocytomatosis!viral!oncogene!homolog!b(mycb)! MYCB!c80701_g2_i1! O35493! CDC!like!kinase!4(Clk4)! CLK4!c93162_g3_i3! Q99638! RAD9!checkpoint!clamp!component!A(RAD9A)! RAD9A!c83932_g1_i3! Q6DGG1! abhydrolase!domain!containing!14b(Abhd14b)! ABHEB!c90565_g1_i2! Q2KJI7! AFG3!like!matrix!AAA!peptidase!subunit!2(AFG3L2)! AFG32!c81559_g1_i1! Q800K6! topoisomerase!(DNA)!II!binding!protein!1!L!homeolog(topbp1.L)! TOB1A!
!
! 83!
c92147_g5_i1! Q8VHI5! vitrin(Vit)! VITRN!c94261_g1_i1! Q96JM7! l(3)mbtElike!3!(Drosophila)(L3MBTL3)! LMBL3!c94460_g1_i7! A0AUS0! WD!repeat,!sterile!alpha!motif!and!UEbox!domain!containing!1(wdsub1)! WSDU1!c83389_g1_i1! Q9P212! phospholipase!C!epsilon!1(PLCE1)! PLCE1!c74096_g1_i1! A2AL36! centriolin(Cntrl)! CNTRL!c95419_g2_i2! Q04913! nuclear!receptor!subfamily!4!group!A!member!1!L!homeolog(nr4a1.L)! NR4A1!c98092_g1_i3! Q8ND30! PPFIA!binding!protein!2(PPFIBP2)! LIPB2!c74205_g2_i1! O96006! zinc!finger!BEDEtype!containing!1(ZBED1)! ZBED1!c94460_g1_i2! A0AUS0! WD!repeat,!sterile!alpha!motif!and!UEbox!domain!containing!1(wdsub1)! WSDU1!c94143_g1_i1! O15230! laminin!subunit!alpha!5(LAMA5)! LAMA5!c93846_g1_i1! Q98SP7! BardetEBiedl!syndrome!2(bbs2)! BBS2!c97886_g1_i1! Q99570! phosphoinositideE3Ekinase!regulatory!subunit!4(PIK3R4)! PI3R4!c90218_g2_i5! O14672! ADAM!metallopeptidase!domain!10(ADAM10)! ADA10!c94912_g1_i7! Q7Z4L5! tetratricopeptide!repeat!domain!21B(TTC21B)! TT21B!c57150_g1_i1! Q2KHM9! KIAA0753(KIAA0753)! K0753!c89918_g2_i2! Q5RGU1! aarF!domain!containing!kinase!3(adck3)! ADCK3!c85502_g1_i1! Q99LJ2! ankyrin!repeat!and!BTB!(POZ)!domain!containing!1(Abtb1)! ABTB1!c91217_g4_i2! Q8CGN4! BCL6!interacting!corepressor(Bcor)! BCOR!c91603_g1_i2! Q9NQQ7! solute!carrier!family!35!member!C2(SLC35C2)! S35C2!c84953_g1_i1! P62597! protection!of!telomeres!1(POT1)! POTE1!c94846_g2_i1! A4IHD2! RAD54Elike!2(rad54l2)! ARIP4!
!
! 84!
c87259_g2_i3! Q9QVP9! PTK2!protein!tyrosine!kinase!2!beta(Ptk2b)! FAK2!
c84189_g1_i1! Q3UES3!tankyrase,!TRF1Einteracting!ankyrinErelated!ADPEribose!polymerase!2(Tnks2)! TNKS2!
c76171_g1_i2! Q8QGQ8! period!circadian!clock!2(PER2)! PER2!c84669_g2_i1! Q6TNS7! RAB,!member!of!RAS!oncogene!familyElike!3(rabl3)! RABL3!c99267_g1_i4! Q6ISB3! grainyhead!like!transcription!factor!2(GRHL2)! GRHL2!c89157_g4_i1! Q6NX31! minichromosome!maintenance!complex!component!7(mcm7)! MCM7!c84606_g1_i1! Q6NTN5! SET!binding!factor!2!L!homeolog(sbf2.L)! MTMRD!c98110_g2_i6! Q9NTG7! sirtuin!3(SIRT3)! SIR3!c95548_g1_i4! Q05858! formin!1(FMN1)! FMN!c92340_g2_i5! Q6NV83! U2!snRNPEassociated!SURP!domain!containing(U2surp)! SR140!c77661_g1_i1! Q9Y238! deleted!in!lung!and!esophageal!cancer!1(DLEC1)! DLEC1!c97924_g2_i1! Q6ZMG9! ceramide!synthase!6(CERS6)! CERS6!c99185_g1_i6! P30414! natural!killer!cell!triggering!receptor(NKTR)! NKTR!c97921_g1_i4! Q9DG12! arylEhydrocarbon!receptor!nuclear!translocator!2(arnt2)! ARNT2!c96178_g1_i6! Q32S26! bromodomain!containing!2(BRD2)! BRD2!c98935_g1_i2! P98175! RNA!binding!motif!protein!10(RBM10)! RBM10!c97374_g1_i1! Q9H9V4! ring!finger!protein!122(RNF122)! RN122!c93576_g1_i4! Q9PU47! PDZ!and!LIM!domain!3(PDLIM3)! PDLI3!c91355_g3_i1! Q2KHR3! glutamine!and!serine!rich!1(QSER1)! QSER1!c84345_g2_i2! P53798! farnesyl!diphosphate!farnesyl!transferase!1(Fdft1)! FDFT!
!
! 85!
c72793_g1_i1! Q9BX63! BRCA1!interacting!protein!CEterminal!helicase!1(BRIP1)! FANCJ!c96888_g1_i1! Q28DR4! histone!cluster!1,!H4a(hist1h4a)! H4!c94073_g1_i1! Q64591! 2,4Edienoyl!CoA!reductase!1,!mitochondrial(Decr1)! DECR!c77861_g1_i1! Q16589! cyclin!G2(CCNG2)! CCNG2!c87171_g1_i4! Q568H3! si:dkeyE23c22.2(si:dkeyE23c22.2)! MD2L2!c92631_g1_i1! Q62656! protein!tyrosine!phosphatase,!receptor!type!Z1(Ptprz1)! PTPRZ!c75404_g2_i1! Q9Y4B5! microtubule!crosslinking!factor!1(MTCL1)! SOGA2!c91111_g1_i1! Q5U2Y1! general!transcription!factor!II!I(Gtf2i)! GTF2I!c93207_g1_i1! A2V9Y8! DEamino!acid!oxidase(DAO)! OXDA!c63662_g1_i2! O08648! mitogenEactivated!protein!kinase!kinase!kinase!4(Map3k4)! M3K4!
c73932_g1_i1! Q60519!
sema!domain,!seven!thrombospondin!repeats!(type!1!and!type!1Elike),!transmembrane!domain!(TM)!and!short!cytoplasmic!domain,!(semaphorin)!5B(Sema5b)! SEM5B!
c96055_g2_i2! Q90Z00! fibroblast!growth!factor!receptor!1a(fgfr1a)! FGR1A!c95892_g2_i6! O76039! cyclin!dependent!kinase!like!5(CDKL5)! CDKL5!c82493_g1_i2! P48509! CD151!molecule!(Raph!blood!group)(CD151)! CD151!c78357_g1_i2! Q5T2W1! PDZ!domain!containing!1(PDZK1)! NHRF3!c90930_g1_i1! Q2KIT4! DnaJ!heat!shock!protein!family!(Hsp40)!member!B4(DNAJB4)! DNJB4!c71795_g1_i1! O60245! protocadherin!7(PCDH7)! PCDH7!c38360_g1_i1! O88898! transformation!related!protein!63(Trp63)! P63!c99705_g2_i3! Q8BYJ6! TBC1!domain!family,!member!4(Tbc1d4)! TBCD4!
!
! 86!
c83700_g1_i2! Q32LE4! gammaEglutamylcyclotransferase(GGCT)! GGCT!c75688_g1_i1! Q9CXC9! ets!variant!5(Etv5)! ETV5!c97548_g2_i2! Q9I9R3! solute!carrier!family!40!(ironEregulated!transporter),!member!1(slc40a1)! S40A1!c99339_g2_i2! Q6UFS5! zinc!finger!protein!503(znf503)! ZN503!c94736_g1_i2! O95363! phenylalanylEtRNA!synthetase!2,!mitochondrial(FARS2)! SYFM!c96983_g1_i4! Q96EX2! ring!finger!protein,!transmembrane!2(RNFT2)! RNFT2!c55568_g1_i1! Q14106! transducer!of!ERBB2,!2(TOB2)! TOB2!c53435_g1_i1! Q9D1G3! hedgehog!acyltransferaseElike(Hhatl)! HHATL!c84507_g1_i2! Q9UNK9! angel!homolog!1(ANGEL1)! ANGE1!
c84711_g1_i1! Q9BX84!transient!receptor!potential!cation!channel!subfamily!M!member!6(TRPM6)! TRPM6!
c97702_g1_i1! Q9HAZ1! CDC!like!kinase!4(CLK4)! CLK4!c63929_g1_i1! Q9W7C5! heparin!binding!EGF!like!growth!factor(HBEGF)! HBEGF!c79516_g1_i1! P47792! SRY!(sex!determining!region!Y)Ebox!19a(sox19a)! SX19A!c81392_g1_i2! Q58EJ9! zgc:110783(zgc:110783)! MOSC1!c92613_g2_i1! Q6F2E7! SRY!(sex!determining!region!Y)Ebox!9(sox9)! SOX9!c75977_g1_i1! P54760! EPH!receptor!B4(EPHB4)! EPHB4!c98406_g2_i3! P35573! amyloEalphaE1,!6Eglucosidase,!4EalphaEglucanotransferase(AGL)! GDE!c79680_g1_i1! Q6DJF8! methyltransferase!like!23!S!homeolog(mettl23.S)! MET23!c89895_g2_i1! Q3SX00! ankyrin!repeat!domain!46(ANKRD46)! ANR46!c87515_g1_i1! Q13535! ATR!serine/threonine!kinase(ATR)! ATR!
!
! 87!
c88699_g3_i1! Q99PP9! tripartite!motifEcontaining!16(Trim16)! TRI16!c92147_g1_i2! Q95LI2! vitrin(VIT)! VITRN!c84160_g1_i1! Q9EQR6! Fanconi!anemia,!complementation!group!G(Fancg)! FANCG!
c99550_g1_i4! Q3EC11!Ankyrin!repeat!family!protein!with!DHHC!zinc!finger!domainEcontaining!protein(AT2G14255)! ZDHC2!
c61036_g1_i4! Q2VIU1! inhibitor!of!DNA!binding!2,!HLH!protein(ID2)! ID2!c89784_g1_i2! O15042! U2!snRNP!associated!SURP!domain!containing(U2SURP)! SR140!c94948_g1_i1! Q8BHG1! nardilysin,!NEarginine!dibasic!convertase,!NRD!convertase!1(Nrd1)! NRDC!c83078_g2_i1! Q1RMR0! RNA!polymerase!III!subunit!G!like(POLR3GL)! RPC7L!c97681_g1_i2! Q7TNK0! serine!incorporator!1(Serinc1)! SERC1!c86678_g1_i1! Q9R0M3! sushiErepeatEcontaining!protein(Srpx)! SRPX!
c99772_g1_i1! A6NHR9!structural!maintenance!of!chromosomes!flexible!hinge!domain!containing!1(SMCHD1)! SMHD1!
c86269_g2_i1! Q5XI50! membrane!associated!ringECHEtype!finger!7(March7)! MARH7!c90652_g1_i4! Q7SXM0! histone!deacetylase!8(hdac8)! HDAC8!c99192_g1_i4! Q96PU4! ubiquitin!like!with!PHD!and!ring!finger!domains!2(UHRF2)! UHRF2!c85845_g1_i3! Q3UZ18! interactor!of!little!elongation!complex!ELL!subunit!2(Ice2)! NARG2!
c80210_g2_i1! Q8BHK1!non!imprinted!in!PraderEWilli/Angelman!syndrome!1!homolog!(human)(Nipa1)! NIPA1!
c96385_g2_i3! Q502L1! acylECoA!binding!domain!containing!5a(acbd5a)! ACB5A!c67860_g1_i1! P05153! phosphoenolpyruvate!carboxykinase!1!(soluble)(PCK1)! PCKGC!
!
! 88!
c90260_g1_i1! P54277! PMS1!homolog!1,!mismatch!repair!system!component(PMS1)! PMS1!c66137_g1_i1! Q96RT7! tubulin!gamma!complex!associated!protein!6(TUBGCP6)! GCP6!
c98624_g1_i2! Q6F6B3!tetratricopeptide!repeat,!ankyrin!repeat!and!coiledEcoil!containing!1(Tanc1)! TANC1!
c95873_g1_i6! Q6GLT5! makorin!ring!finger!protein!1!S!homeolog(mkrn1.S)! MKRN1!c94765_g1_i1! Q5VT97! synapse!defective!Rho!GTPase!homolog!2(SYDE2)! SYDE2!c61036_g1_i1! Q2VIU1! inhibitor!of!DNA!binding!2,!HLH!protein(ID2)! ID2!c90555_g1_i1! A0JMV4! RNA!binding!motif!protein!5!L!homeolog(rbm5.L)! RBM5A!c82623_g2_i2! Q7SYD5! SEC31!homolog!A,!COPII!coat!complex!component(sec31a)! SC31A!c59133_g1_i1! Q5T0B9! zinc!finger!protein!362(ZNF362)! ZN362!c95695_g1_i2! Q6PJI9! WD!repeat!domain!59(WDR59)! WDR59!c92760_g6_i3! Q90701! TEA!domain!family!member!3(TEAD3)! TEAD3!c98799_g2_i2! P32018! collagen,!type!XIV,!alpha!1(COL14A1)! COEA1!c8435_g1_i1! Q2TBM7! matrix!metallopeptidase!23B(MMP23B)! MMP23!c88725_g1_i1! Q7RTR2! NLR!family!CARD!domain!containing!3(NLRC3)! NLRC3!c90320_g2_i1! Q2EI20! RE1Esilencing!transcription!factor(rest)! REST!c92506_g1_i6! Q0P5H7! arginylEtRNA!synthetase!2,!mitochondrial(RARS2)! SYRM!c77931_g1_i1! Q9NXW2! DnaJ!heat!shock!protein!family!(Hsp40)!member!B12(DNAJB12)! DJB12!c78945_g1_i2! P20585! mutS!homolog!3(MSH3)! MSH3!c53357_g1_i1! Q9Y6J0! calcineurin!binding!protein!1(CABIN1)! CABIN!c90890_g1_i1! Q8N442! GUF1!homolog,!GTPase(GUF1)! GUF1!
!
! 89!
c91890_g1_i2! P83626! tumor!necrosis!factor!receptor!superfamily,!member!26(Tnfrsf26)! TNR26!c92911_g1_i1! A4IGK4! RNA!binding!motif!protein!5(rbm5)! RBM5!c94642_g1_i4! Q8BJE2! butyrophilinElike!9(Btnl9)! BTNL9!c88739_g2_i3! Q62857! DNAEdamage!inducible!transcript!3(Ddit3)! DDIT3!c79532_g1_i1! O95822! malonylECoA!decarboxylase(MLYCD)! DCMC!c74116_g1_i1! Q96RY7! intraflagellar!transport!140(IFT140)! IF140!c89823_g1_i3! A7MC64! reticulon!1(rtn1)! RTN1!c92166_g1_i1! Q13145! BMP!and!activin!membrane!bound!inhibitor(BAMBI)! BAMBI!c85878_g2_i1! Q99081! transcription!factor!12(TCF12)! HTF4!c98452_g1_i2! Q69ZN7! myoferlin(Myof)! MYOF!c96101_g1_i1! Q8BVW0! glucosidase,!alpha;!neutral!C(Ganc)! GANC!c80346_g2_i4! Q90VV1! hes!family!bHLH!transcription!factor!4!S!homeolog(hes4.S)! HES4B!c95572_g1_i1! O75208! coenzyme!Q9(COQ9)! COQ9!c96203_g1_i1! Q14678! KN!motif!and!ankyrin!repeat!domains!1(KANK1)! KANK1!
c96465_g2_i1! Q92184!ST6!(alphaENEacetylEneuraminylE2,3EbetaEgalactosylE1,3)ENEacetylgalactosaminide!alphaE2,6Esialyltransferase!2(ST6GALNAC2)! SIA7B!
c91548_g1_i1! Q92562! FIG4!phosphoinositide!5Ephosphatase(FIG4)! FIG4!c85205_g2_i5! Q9UNF0! protein!kinase!C!and!casein!kinase!substrate!in!neurons!2(PACSIN2)! PACN2!c80519_g1_i1! Q14678! KN!motif!and!ankyrin!repeat!domains!1(KANK1)! KANK1!c81529_g1_i1! Q6DEY8! TBC1!domain!family!member!31(tbc1d31)! WDR67!c98074_g1_i7! Q5S007! leucine!rich!repeat!kinase!2(LRRK2)! LRRK2!
!
! 90!
c88325_g1_i2! Q95221! inositol!hexakisphosphate!kinase!2(IP6K2)! IP6K2!c81954_g2_i3! B4F7A7! centrosomal!protein!57(Cep57)! CEP57!c92910_g3_i1! Q13283! G3BP!stress!granule!assembly!factor!1(G3BP1)! G3BP1!c73646_g1_i1! Q5RG49! aminoadipateEsemialdehyde!dehydrogenase(aasdh)! ACSF4!c89954_g2_i6! P04897! G!protein!subunit!alpha!i2(Gnai2)! GNAI2!c98943_g1_i3! Q9P2K8! eukaryotic!translation!initiation!factor!2!alpha!kinase!4(EIF2AK4)! E2AK4!c78586_g1_i1! Q90ZE4! presenilin!2(psen2)! PSN2!c94530_g1_i1! Q9BV35! solute!carrier!family!25!member!23(SLC25A23)! SCMC3!c92447_g1_i5! Q68DD2! phospholipase!A2!group!IVF(PLA2G4F)! PA24F!
c18924_g1_i1! Q96QT4!transient!receptor!potential!cation!channel!subfamily!M!member!7(TRPM7)! TRPM7!
c99716_g1_i3! Q7T163! kinase!DEinteracting!substrate!220b(kidins220b)! KDIS!c76566_g1_i2! Q96T23! remodeling!and!spacing!factor!1(RSF1)! RSF1!c85227_g1_i1! Q8MJJ7! decapping!enzyme,!scavenger(DCPS)! DCPS!c96748_g1_i3! Q14995! nuclear!receptor!subfamily!1!group!D!member!2(NR1D2)! NR1D2!
c89290_g2_i1! Q15291!RB!binding!protein!5,!histone!lysine!methyltransferase!complex!subunit(RBBP5)! RBBP5!
c93035_g1_i1! Q8BKE9! intraflagellar!transport!74(Ift74)! IFT74!c97829_g1_i5! Q8TDJ6! Dmx!like!2(DMXL2)! DMXL2!c94347_g1_i5! Q8WYL5! slingshot!protein!phosphatase!1(SSH1)! SSH1!c94717_g1_i2! Q61576! FK506!binding!protein!10(Fkbp10)! FKB10!
!
! 91!
c77369_g1_i1! Q07352! ZFP36!ring!finger!protein!like!1(ZFP36L1)! TISB!c93102_g1_i1! Q96N67! dedicator!of!cytokinesis!7(DOCK7)! DOCK7!c93773_g1_i2! Q6DEJ6! major!facilitator!superfamily!domain!containing!2ab(mfsd2ab)! MF2AB!c170429_g1_i1! Q8WYQ9! zinc!finger!CCHCEtype!containing!14(ZCCHC14)! ZCH14!c86989_g2_i2! Q8JHI3! ADPEribosylation!factorElike!13b(arl13b)! AR13B!
c82958_g1_i2! P51532!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!a,!member!4(SMARCA4)! SMCA4!
c87462_g1_i3! Q14151! scaffold!attachment!factor!B2(SAFB2)! SAFB2!
c93972_g1_i1! Q8BHD8!proteinELEisoaspartate!(DEaspartate)!OEmethyltransferase!domain!containing!2(Pcmtd2)! PCMD2!
c97765_g1_i2! Q8VHQ9! acylECoA!thioesterase!11(Acot11)! ACO11!c95073_g3_i2! Q3UHU5! microtubule!crosslinking!factor!1(Mtcl1)! SOGA2!c91544_g1_i5! Q8C9M2! coiledEcoil!domain!containing!15(Ccdc15)! CCD15!c92236_g3_i2! P38533! heat!shock!factor!2(Hsf2)! HSF2!c61036_g1_i3! P41137! inhibitor!of!DNA!binding!2,!HLH!protein(Id2)! ID2!c97498_g1_i2! Q9NUJ3! tEcomplex!11!like!1(TCP11L1)! T11L1!c75119_g1_i1! Q9ULY5! CEtype!lectin!domain!family!4!member!E(CLEC4E)! CLC4E!c99706_g1_i1! P35054! transforming!growth!factor,!beta!receptor!III(TGFBR3)! TGBR3!c89328_g1_i1! Q9WU79! proline!dehydrogenase(Prodh)! PROD!c87301_g1_i9! P98166! very!low!density!lipoprotein!receptor(Vldlr)! VLDLR!c81868_g1_i1! Q5E9Z7! RNA!polymerase!III!subunit!D(POLR3D)! RPC4!
!
! 92!
c96101_g1_i4! Q8TET4! glucosidase!alpha,!neutral!C(GANC)! GANC!c95071_g1_i1! Q08BN9! neurexophilin!and!PCEesterase!domain!family,!member!3(nxpe3)! NXPE3!c98787_g2_i5! Q9D666! Sad1!and!UNC84!domain!containing!1(Sun1)! SUN1!c77371_g1_i1! Q9D915! RIKEN!cDNA!1810011O10!gene(1810011O10Rik)! CH004!c98820_g1_i1! P98160! heparan!sulfate!proteoglycan!2(HSPG2)! PGBM!c88432_g1_i1! Q5G872! signal!peptide,!CUB!domain,!EGFElike!2(scube2)! SCUB2!c89488_g1_i1! Q8BXB6! solute!carrier!organic!anion!transporter!family,!member!2b1(Slco2b1)! SO2B1!c87301_g2_i1! P98165! very!low!density!lipoprotein!receptor(VLDLR)! VLDLR!c99655_g1_i4! Q642P2! dopey!family!member!2!S!homeolog(dopey2.S)! DOP2!c91890_g1_i4! Q9QZM4! tumor!necrosis!factor!receptor!superfamily,!member!10b(Tnfrsf10b)! TR10B!c88260_g2_i1! Q12873! chromodomain!helicase!DNA!binding!protein!3(CHD3)! CHD3!c82067_g1_i2! Q9BSD7! nucleosideEtriphosphatase,!cancerErelated(NTPCR)! NTPCR!c96889_g3_i2! O60443! DFNA5,!deafness!associated!tumor!suppressor(DFNA5)! DFNA5!c92799_g1_i4! Q9Y2M2! ssuE2!homolog!(C.!elegans)(SSUH2)! SSUH2!c98406_g2_i1! P35573! amyloEalphaE1,!6Eglucosidase,!4EalphaEglucanotransferase(AGL)! GDE!
c83306_g1_i1! B2ZFP3!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!aElike!1(smarcal1)! SMAL1!
c99655_g1_i5! Q642P2! dopey!family!member!2!S!homeolog(dopey2.S)! DOP2!c81124_g1_i4! Q6PZ05! autophagy!related!4A!cysteine!peptidase(ATG4A)! ATG4A!c86267_g1_i3! O15297! protein!phosphatase,!Mg2+/Mn2+!dependent!1D(PPM1D)! PPM1D!c86387_g2_i1! A1L3F4! mexE3!RNA!binding!family!member!B!S!homeolog(mex3b.S)! MEX3B!
!
! 93!
c93049_g1_i3! O14975! solute!carrier!family!27!member!2(SLC27A2)! S27A2!c82129_g1_i1! A5D7F6! mastermind!like!transcriptional!coactivator!2(MAML2)! MAML2!c95419_g3_i1! Q04913! nuclear!receptor!subfamily!4!group!A!member!1!L!homeolog(nr4a1.L)! NR4A1!c79993_g1_i1! Q7SY21! transcriptional!adaptor!3!(NGG1!homolog,!yeast)Elike(tada3l)! TADA3!c92036_g3_i3! C0H8I2! SET!domain!containing!6(setd6)! SETD6!c89174_g6_i1! Q04678! structure!specific!recognition!protein!1(SSRP1)! SSRP1!c89898_g2_i2! P97367! Meis!homeobox!2(Meis2)! MEIS2!c90028_g1_i1! Q6P1B1! XEprolyl!aminopeptidase!(aminopeptidase!P)!1,!soluble(Xpnpep1)! XPP1!c89174_g6_i4! Q04678! structure!specific!recognition!protein!1(SSRP1)! SSRP1!c64353_g1_i1! Q80WC3! trinucleotide!repeat!containing!18(Tnrc18)! TNC18!c99032_g1_i1! O15042! U2!snRNP!associated!SURP!domain!containing(U2SURP)! SR140!c85590_g1_i2! O60469! DS!cell!adhesion!molecule(DSCAM)! DSCAM!c46324_g1_i1! Q7ZVS9! vEmyc!avian!myelocytomatosis!viral!oncogene!homolog!b(mycb)! MYCB!c84431_g4_i1! Q9H3R0! lysine!demethylase!4C(KDM4C)! KDM4C!c99300_g1_i1! Q7TSH2! phosphorylase!kinase!beta(Phkb)! KPBB!c91273_g1_i1! Q494U1! pleckstrin!homology!domain!containing!N1(PLEKHN1)! PKHN1!c82052_g2_i1! Q13609! deoxyribonuclease!1!like!3(DNASE1L3)! DNSL3!c79554_g1_i6! P20357! microtubuleEassociated!protein!2(Map2)! MAP2!c88388_g1_i2! Q8BRT1! CLIP!associating!protein!2(Clasp2)! CLAP2!c88320_g1_i2! Q6P3P1! Tax1!(human!TEcell!leukemia!virus!type!I)!binding!protein!1(tax1bp1)! TAXB1!c96040_g1_i1! Q52KB6! C2!calciumEdependent!domain!containing!3(C2cd3)! C2CD3!
!
! 94!
c97656_g1_i1! Q9JLZ3! AU!RNA!binding!protein/enoylEcoenzyme!A!hydratase(Auh)! AUHM!c95547_g2_i1! Q99JP0! mitogenEactivated!protein!kinase!kinase!kinase!kinase!3(Map4k3)! M4K3!c90235_g4_i2! Q16787! laminin!subunit!alpha!3(LAMA3)! LAMA3!c83356_g2_i1! Q96FN4! copine!2(CPNE2)! CPNE2!c48499_g1_i1! P30305! cell!division!cycle!25B(CDC25B)! MPIP2!c61036_g1_i2! P41137! inhibitor!of!DNA!binding!2,!HLH!protein(Id2)! ID2!c80701_g1_i1! P22518! CDCElike!kinase!1(Clk1)! CLK1!
c92514_g2_i3! Q4L1J4!membrane!associated!guanylate!kinase,!WW!and!PDZ!domain!containing!1(Magi1)! MAGI1!
c59840_g1_i1! B3DJM5! teashirt!zinc!finger!homeobox!1(tshz1)! TSH1!c96819_g1_i1! Q7TT36! adhesion!G!proteinEcoupled!receptor!A3(Adgra3)! GP125!c98679_g1_i1! P39689! cyclinEdependent!kinase!inhibitor!1A!(P21)(Cdkn1a)! CDN1A!c86203_g1_i1! Q08BY0! NADH!dehydrogenase!(ubiquinone)!complex!I,!assembly!factor!7(ndufaf7)! NDUF7!c96280_g1_i1! Q05AM5! elongator!acetyltransferase!complex!subunit!2(elp2)! ELP2!c89833_g2_i4! O75164! lysine!demethylase!4A(KDM4A)! KDM4A!c93644_g1_i2! Q9Y250! leucine!zipper!tumor!suppressor!1(LZTS1)! LZTS1!c95250_g2_i1! Q8CC12! congenital!dyserythropoietic!anemia,!type!I!(human)(Cdan1)! CDAN1!c89029_g2_i1! Q7T3Q2! cysteine!rich!transmembrane!BMP!regulator!1!(chordinElike)(crim1)! CRIM1!c89426_g2_i1! Q9UJX2! cell!division!cycle!23(CDC23)! CDC23!c67831_g1_i1! Q99JW2! aminoacylase!1(Acy1)! ACY1!c79991_g1_i1! Q9GZX9! twisted!gastrulation!BMP!signaling!modulator!1(TWSG1)! TWSG1!
!
! 95!
c86421_g1_i2! P30825! solute!carrier!family!7!member!1(SLC7A1)! CTR1!c94154_g1_i2! P48728! aminomethyltransferase(AMT)! GCST!c96880_g1_i7! Q8BH75! ring!finger!protein!41(Rnf41)! RNF41!c97507_g1_i5! O95405! zinc!finger!FYVEEtype!containing!9(ZFYVE9)! ZFYV9!c94838_g1_i1! O60343! TBC1!domain!family!member!4(TBC1D4)! TBCD4!c88015_g1_i1! Q8C9B9! death!inducerEobliterator!1(Dido1)! DIDO1!
c94604_g1_i1! P62046!leucineErich!repeats!and!calponin!homology!(CH)!domain!containing!1(Lrch1)! LRCH1!
c90282_g1_i2! Q9NWM0! spermine!oxidase(SMOX)! SMOX!c69129_g1_i1! O95198! kelch!like!family!member!2(KLHL2)! KLHL2!c96802_g1_i1! Q6P7B7! zinc!finger!FYVEEtype!containing!27(Zfyve27)! ZFY27!c95495_g1_i1! Q8CH77! neuron!navigator!1(Nav1)! NAV1!c99247_g1_i1! P43155! carnitine!OEacetyltransferase(CRAT)! CACP!c99150_g2_i2! Q9IBG7! kielin/chordinElike!protein!L!homeolog(kcp.L)! KCP!c84917_g1_i1! Q0VD50! nicotinamide!nucleotide!adenylyltransferase!1(NMNAT1)! NMNA1!c84431_g1_i1! Q5RD88! lysine!demethylase!4A(KDM4A)! KDM4A!c82864_g1_i3! Q8K4Q6! nei!endonuclease!VIIIElike!1!(E.!coli)(Neil1)! NEIL1!c96320_g1_i2! P51578! purinergic!receptor!P2X!5(P2rx5)! P2RX5!
c92280_g1_i1! Q9NZ52!golgi!associated,!gamma!adaptin!ear!containing,!ARF!binding!protein!3(GGA3)! GGA3!
c79189_g1_i3! Q64287! interferon!regulatory!factor!4(Irf4)! IRF4!
!
! 96!
c89540_g1_i5! Q5RIC0! elongator!acetyltransferase!complex!subunit!3(elp3)! ELP3!c94757_g1_i3! Q01432! adenosine!monophosphate!deaminase!3(AMPD3)! AMPD3!c84846_g1_i1! Q3SZ48! transmembrane!protein!55A(TMEM55A)! TM55A!c91927_g1_i1! P17177! sterol!26Ehydroxylase,!mitochondrial(CYP27A1)! CP27A!c91927_g1_i6! P17178! cytochrome!P450,!family!27,!subfamily!a,!polypeptide!1(Cyp27a1)! CP27A!c87242_g2_i1! Q9H2F5! enhancer!of!polycomb!homolog!1(EPC1)! EPC1!c81517_g1_i1! P16236! vErel!avian!reticuloendotheliosis!viral!oncogene!homolog(REL)! REL!c95441_g2_i2! Q5R795! mitochondrial!fission!factor(MFF)! MFF!c80345_g1_i2! Q9NPI5! nicotinamide!riboside!kinase!2(NMRK2)! NRK2!c91577_g1_i3! Q9Z2A7! diacylglycerol!OEacyltransferase!1(Dgat1)! DGAT1!c99159_g4_i2! Q9BZ95! WolfEHirschhorn!syndrome!candidate!1Elike!1(WHSC1L1)! NSD3!c77248_g1_i1! P10157! vEets!avian!erythroblastosis!virus!E26!oncogene!homolog!2(ETS2)! ETS2!c78306_g1_i2! D3Z3C6! zinc!finger,!AN1Etype!domain!4(Zfand4)! ZFAN4!c99392_g1_i2! Q4GZT3! polycystin!2,!transient!receptor!potential!cation!channel(PKD2)! PKD2!c67901_g1_i1! P85515! ARP1!actinErelated!protein!1!homolog!A,!centractin!alpha(Actr1a)! ACTZ!c98105_g1_i1! O14977! antizyme!inhibitor!1(AZIN1)! AZIN1!c62881_g1_i1! Q6KFX9! RFNG!OEfucosylpeptide!3EbetaENEacetylglucosaminyltransferase(rfng)! RFNG!c91396_g1_i1! Q66IV5! actinErelated!protein!2/3!complex!inhibitor!L!homeolog(arpin.L)! CO038!c68566_g1_i2! Q9H2K2! tankyrase!2(TNKS2)! TNKS2!c78865_g1_i1! Q08209! protein!phosphatase!3!catalytic!subunit!alpha(PPP3CA)! PP2BA!c99319_g1_i7! Q5VU43! phosphodiesterase!4D!interacting!protein(PDE4DIP)! MYOME!
!
! 97!
c84718_g1_i4! Q5RCJ6! chromosome!15!open!reading!frame,!human!C15orf52(C15H15orf52)! CO052!
c92843_g1_i1! A5PLK2!phospholysine!phosphohistidine!inorganic!pyrophosphate!phosphatase(lhpp)! LHPP!
c19548_g1_i1! Q5FVP5! WD!repeat!domain!89(Wdr89)! WDR89!c96316_g1_i1! Q08DX0! sorting!nexin!29(SNX29)! SNX29!c83422_g1_i1! A0JM13! C2!calciumEdependent!domain!containing!3(c2cd3)! C2CD3!c85205_g2_i1! Q99JB8! protein!kinase!C!and!casein!kinase!substrate!in!neurons!3(Pacsin3)! PACN3!c82972_g3_i2! Q9BYZ6! Rho!related!BTB!domain!containing!2(RHOBTB2)! RHBT2!c85048_g1_i1! Q9C0B7! transport!and!golgi!organization!6!homolog(TANGO6)! TNG6!c65593_g1_i1! Q9JI85! nucleobindin!2(Nucb2)! NUCB2!c98779_g2_i2! Q9UHP3! ubiquitin!specific!peptidase!25(USP25)! UBP25!c91864_g1_i2! P35251! replication!factor!C!subunit!1(RFC1)! RFC1!c94582_g2_i1! Q803G5! SAMM50!sorting!and!assembly!machinery!component(samm50)! SAM5A!c91085_g1_i3! A7YWP4! histidine!ammoniaElyase(HAL)! HUTH!
c95137_g1_i1! A7Z019!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!a,!member!4(SMARCA4)! SMCA4!
c85831_g1_i1! Q96JM2! zinc!finger!protein!462(ZNF462)! ZN462!c95744_g1_i1! Q9NRR4! drosha!ribonuclease!III(DROSHA)! RNC!c94154_g1_i1! P48728! aminomethyltransferase(AMT)! GCST!c98502_g1_i1! Q9DB00! gonE4Elike!(C.elegans)(Gon4l)! GON4L!c86564_g1_i1! Q14094! cyclin!I(CCNI)! CCNI!
!
! 98!
c81864_g2_i6! Q13277! syntaxin!3(STX3)! STX3!c84832_g2_i1! Q9TTR7! nuclear!receptor!subfamily!2!group!F!member!2(NR2F2)! COT2!c98121_g1_i1! P97865! peroxisomal!biogenesis!factor!7(Pex7)! PEX7!c77069_g1_i1! Q7ZWZ4! zinc!finger!protein!238,!gene!2!L!homeolog(znf238.2.L)! ZB182!c92110_g1_i1! Q5ZLR1! wntless!Wnt!ligand!secretion!mediator(WLS)! WLS!c89820_g2_i2! P13346! FBJ!osteosarcoma!oncogene!B(Fosb)! FOSB!c89476_g1_i1! Q5ZKM0! dystrobrevin!binding!protein!1(DTNBP1)! DTBP1!c77383_g1_i2! O08858! somatostatin!receptor!5(Sstr5)! SSR5!c80209_g1_i2! P12798! phosphorylase!kinase!regulatory!subunit!beta(PHKB)! KPBB!c98429_g1_i1! Q9UKG9! carnitine!OEoctanoyltransferase(CROT)! OCTC!c87261_g2_i1! Q9DC22! DDB1!and!CUL4!associated!factor!6(Dcaf6)! DCAF6!c66187_g2_i1! Q05826! CCAAT/enhancer!binding!protein!(C/EBP),!beta(CEBPB)! CEBPB!c72236_g1_i1! P25930! CEXEC!motif!chemokine!receptor!4(CXCR4)! CXCR4!c82338_g1_i1! Q61823! programmed!cell!death!4(Pdcd4)! PDCD4!c85518_g1_i3! Q0II87! transcription!factor!A,!mitochondrial(TFAM)! TFAM!c80773_g2_i2! Q3LXA3! triokinase!and!FMN!cyclase(TKFC)! DHAK!c99006_g3_i2! Q90ZK6! serine/threonineEprotein!kinase!receptor(ATVR1)! ACVR1!c83435_g1_i1! Q66GT5! protein!tyrosine!phosphatase,!mitochondrial!1(Ptpmt1)! PTPM1!c95419_g3_i2! Q04913! nuclear!receptor!subfamily!4!group!A!member!1!L!homeolog(nr4a1.L)! NR4A1!c89174_g3_i1! Q2THW9! zinc!finger!DHHCEtype!containing!5(ZDHHC5)! ZDHC5!
!
! 99!
c95794_g1_i1! Q8NEU8!adaptor!protein,!phosphotyrosine!interacting!with!PH!domain!and!leucine!zipper!2(APPL2)! DP13B!
c79113_g1_i3! Q5EA53! general!transcription!factor!IIF!subunit!1(GTF2F1)! T2FA!c99770_g2_i1! Q2PW47! mediator!complex!subunit!24(med24)! MED24!c93538_g1_i1! P35659! DEK!protoEoncogene(DEK)! DEK!c79780_g1_i1! O89113! immediate!early!response!5(Ier5)! IER5!c92981_g2_i2! Q8JGT4! uncE5!netrin!receptor!B!L!homeolog(unc5b.L)! UNC5B!c87602_g1_i1! Q9R0P3! esterase!D/formylglutathione!hydrolase(Esd)! ESTD!c75616_g1_i1! Q503G8! solute!carrier!family!38,!member!6(slc38a6)! S38A6!c71883_g1_i2! Q12873! chromodomain!helicase!DNA!binding!protein!3(CHD3)! CHD3!c87690_g1_i9! Q2KHT3! CEtype!lectin!domain!family!16!member!A(CLEC16A)! CL16A!c78046_g1_i1! Q8IYB1! MabE21!domain!containing!2(MB21D2)! M21D2!c97774_g2_i2! Q8R5G7! ArfGAP!with!RhoGAP!domain,!ankyrin!repeat!and!PH!domain!3(Arap3)! ARAP3!c91335_g3_i1! Q969R8! integrin!alpha!FGEGAP!repeat!containing!2(ITFG2)! ITFG2!c74051_g1_i1! O42368! homeobox!B3a(hoxb3a)! HXB3A!c82226_g1_i1! Q8IYT8! uncE51!like!autophagy!activating!kinase!2(ULK2)! ULK2!c81464_g1_i1! C6FG12! NLR!family!CARD!domain!containing!5(nlrc5)! NLRC5!c92948_g1_i3! Q6DC02! potassium!channel!tetramerization!domain!containing!15b(kctd15b)! KCD15!c99321_g1_i4! Q7Z3K3! pogo!transposable!element!with!ZNF!domain(POGZ)! POGZ!c81420_g3_i1! Q924I2! mitogenEactivated!protein!kinase!kinase!kinase!kinase!3(Map4k3)! M4K3!c99555_g1_i3! Q99549! MEphase!phosphoprotein!8(MPHOSPH8)! MPP8!
!
! 100!
c99930_g1_i1! A5WUT8! ectopic!PEgranules!autophagy!protein!5!homolog!(C.!elegans)(epg5)! EPG5!c99052_g1_i1! O75385! uncE51!like!autophagy!activating!kinase!1(ULK1)! ULK1!c85681_g1_i1! O19182! potassium!voltageEgated!channel!subfamily!J!member!2(KCNJ2)! IRK2!c91718_g1_i2! Q4U0G1! cytoplasmic!linker!associated!protein!1!L!homeolog(clasp1.L)! CLA1A!c91068_g1_i2! Q2TBT3! enoylECoA!hydratase!domain!containing!2(ECHDC2)! ECHD2!c99075_g1_i1! P84104! serine/arginineErich!splicing!factor!3(Srsf3)! SRSF3!c87397_g3_i1! Q8R4C0! calpain!5(Capn5)! CAN5!c69886_g1_i1! Q5R7X2! U2!snRNP!associated!SURP!domain!containing(U2SURP)! SR140!c96709_g4_i1! Q1LV22! family!with!sequence!similarity!214,!member!A(fam214a)! F214A!c98078_g1_i4! A8E657! aminoadipateEsemialdehyde!synthase(AASS)! AASS!c87829_g1_i1! P0C548! patatinElike!phospholipase!domain!containing!2(Pnpla2)! PLPL2!c94143_g1_i4! O15230! laminin!subunit!alpha!5(LAMA5)! LAMA5!c79735_g1_i1! Q6NZ13! neuroblastoma!1,!DAN!family!BMP!antagonist(nbl1)! NBL1!c96908_g1_i1! Q9BY12! SEphase!cyclin!A!associated!protein!in!the!ER(SCAPER)! SCAPE!c90725_g1_i3! Q9FKK7! xylose!isomerase!family!protein(AT5G57655)! XYLA!c98348_g1_i1! Q9UIF8! bromodomain!adjacent!to!zinc!finger!domain!2B(BAZ2B)! BAZ2B!c99363_g4_i1! Q8WVV9! heterogeneous!nuclear!ribonucleoprotein!L!like(HNRNPLL)! HNRLL!c79201_g1_i1! Q9NRG4! SET!and!MYND!domain!containing!2(SMYD2)! SMYD2!c60686_g1_i1! Q66KY3! cutA!divalent!cation!tolerance!homolog!L!homeolog(cuta.L)! CUTA!c90798_g1_i2! Q1JPZ3! vEsrc!avian!sarcoma!(SchmidtERuppin!AE2)!viral!oncogene!homolog(src)! SRC!c77164_g1_i6! A2AGX3! PR!domain!containing!11(Prdm11)! PRD11!
!
! 101!
c91736_g1_i3! Q3U3Q1! uncE51Elike!kinase!3(Ulk3)! ULK3!c98489_g1_i3! A2BIJ3! BSD!domain!containing!1(bsdc1)! BSDC1!c98485_g1_i2! Q9Z2V5! histone!deacetylase!6(Hdac6)! HDAC6!c93608_g1_i1! P35475! iduronidase,!alphaELE(IDUA)! IDUA!c72755_g1_i1! Q96N67! dedicator!of!cytokinesis!7(DOCK7)! DOCK7!c84388_g1_i1! Q8BH95! enoyl!Coenzyme!A!hydratase,!short!chain,!1,!mitochondrial(Echs1)! ECHM!c88388_g3_i1! Q6NYW6! cytoplasmic!linker!associated!protein!2(clasp2)! CLAP2!c95320_g3_i1! Q8NCW6! polypeptide!NEacetylgalactosaminyltransferase!11(GALNT11)! GLT11!c78534_g1_i2! Q1JP73! chromosome!8!open!reading!frame,!human!C9orf64(C8H9orf64)! CI064!c98080_g3_i2! Q6P7W0! SUMO/sentrin!specific!peptidase!6(Senp6)! SENP6!c93412_g1_i1! Q53EL6! programmed!cell!death!4!(neoplastic!transformation!inhibitor)(PDCD4)! PDCD4!c98800_g1_i1! Q3U7R1! extended!synaptotagminElike!protein!1(Esyt1)! ESYT1!c75680_g1_i1! Q8TCU4! ALMS1,!centrosome!and!basal!body!associated!protein(ALMS1)! ALMS1!c89178_g1_i1! Q9H9B1! euchromatic!histone!lysine!methyltransferase!1(EHMT1)! EHMT1!c96027_g4_i5! A2RT67! DENN/MADD!domain!containing!3(Dennd3)! DEND3!c93654_g1_i1! Q7TQI7! ankyrin!repeat!and!BTB!(POZ)!domain!containing!2(Abtb2)! ABTB2!c98448_g1_i1! Q8NFY4! semaphorin!6D(SEMA6D)! SEM6D!c91806_g1_i1! Q9WV76! adaptorErelated!protein!complex!APE4,!beta!1(Ap4b1)! AP4B1!
c81936_g1_i1! Q15751!HECT!and!RLD!domain!containing!E3!ubiquitin!protein!ligase!family!member!1(HERC1)! HERC1!
c96877_g1_i2! Q7SXN5! dynamin!1Elike(dnm1l)! DNM1L!
!
! 102!
c95355_g2_i2! Q6P823! H3!histone,!family!3B!(H3.3B)(h3f3b)! H33!c87864_g1_i1! Q5U2M8! mediator!of!DNA!damage!checkpoint!1(Mdc1)! MDC1!c86064_g1_i1! Q3T8J9! gonE4!like(GON4L)! GON4L!c99292_g1_i9! Q9D4J7! PHD!finger!protein!6(Phf6)! PHF6!c90966_g1_i1! Q5T0B9! zinc!finger!protein!362(ZNF362)! ZN362!c99630_g1_i2! Q811D0! discs,!large!homolog!1!(Drosophila)(Dlg1)! DLG1!c95353_g1_i1! Q8IVF5! TEcell!lymphoma!invasion!and!metastasis!2(TIAM2)! TIAM2!c66187_g1_i1! P17676! CCAAT/enhancer!binding!protein!beta(CEBPB)! CEBPB!c75732_g1_i1! Q86UC2! radial!spoke!3!homolog(RSPH3)! RSPH3!c89262_g1_i1! Q9Y6A1! protein!OEmannosyltransferase!1(POMT1)! POMT1!c96027_g4_i6! A2RT67! DENN/MADD!domain!containing!3(Dennd3)! DEND3!c94714_g2_i1! Q9NXG6! prolyl!4Ehydroxylase,!transmembrane(P4HTM)! P4HTM!c94737_g4_i1! Q1JPZ3! vEsrc!avian!sarcoma!(SchmidtERuppin!AE2)!viral!oncogene!homolog(src)! SRC!
c96021_g1_i1! Q96QT4!transient!receptor!potential!cation!channel!subfamily!M!member!7(TRPM7)! TRPM7!
c95666_g1_i1! Q7Z3E5! armadillo!repeat!containing!9(ARMC9)! ARMC9!c98696_g1_i2! Q8IX12! cell!division!cycle!and!apoptosis!regulator!1(CCAR1)! CCAR1!c94372_g1_i1! Q99814! endothelial!PAS!domain!protein!1(EPAS1)! EPAS1!c93950_g1_i3! A6QNT4! family!with!sequence!similarity!120B(FAM120B)! F120B!c95262_g1_i1! Q9UJX5! anaphase!promoting!complex!subunit!4(ANAPC4)! APC4!c99012_g1_i2! P16039! nucleophosmin!(nucleolar!phosphoprotein!B23,!numatrin)(NPM1)! NPM!
!
! 103!
c99705_g2_i1! Q8BYJ6! TBC1!domain!family,!member!4(Tbc1d4)! TBCD4!c89692_g1_i4! Q66JG1! damageEspecific!DNA!binding!protein!2(ddb2)! DDB2!c85095_g1_i1! Q9H9V4! ring!finger!protein!122(RNF122)! RN122!c93153_g3_i5! O14595! CTD!small!phosphatase!2(CTDSP2)! CTDS2!c97023_g1_i1! Q9TT15! voltage!dependent!anion!channel!1(VDAC1)! VDAC1!c84733_g1_i1! P25207! nuclear!transcription!factor!Y,!beta(NFYB)! NFYB!c80314_g1_i1! P08247! synaptophysin(SYP)! SYPH!c85837_g1_i1! Q86WG5! SET!binding!factor!2(SBF2)! MTMRD!c94936_g3_i1! Q8TDG4! helicase,!POLQElike(HELQ)! HELQ!c88871_g1_i4! Q7SXR3! macrophage!erythroblast!attacher(maea)! MAEA!c81876_g1_i2! Q63ZY7! ubiquitouslyEexpressed,!prefoldinElike!chaperone(Uxt)! UXT!c99699_g1_i1! Q6NTN5! SET!binding!factor!2!L!homeolog(sbf2.L)! MTMRD!c80167_g1_i1! P35250! replication!factor!C!subunit!2(RFC2)! RFC2!c98064_g1_i1! P0DJJ3! SH3Edomain!GRB2Elike!(endophilin)!interacting!protein!1(Sgip1)! SGIP1!c80246_g1_i1! Q6DG38! glycerolE3Ephosphate!acyltransferase!3(gpat3)! GPAT3!c98721_g1_i1! Q13118! Kruppel!like!factor!10(KLF10)! KLF10!c87554_g4_i2! Q80YQ8! required!for!meiotic!nuclear!division!5!homolog!A(Rmnd5a)! RMD5A!c84180_g3_i1! Q14643! inositol!1,4,5Etrisphosphate!receptor!type!1(ITPR1)! ITPR1!c83385_g4_i1! Q8WN96! inositol!1,4,5Etrisphosphate!receptor!type!2(ITPR2)! ITPR2!c71080_g1_i1! Q6ZUM4! Rho!GTPase!activating!protein!27(ARHGAP27)! RHG27!c98640_g1_i1! A6QLY7! PBX!homeobox!interacting!protein!1(PBXIP1)! PBIP1!
!
! 104!
c86948_g1_i5! O43189! PHD!finger!protein!1(PHF1)! PHF1!c95094_g3_i1! Q6DN12! multiple!C2!and!transmembrane!domain!containing!2(MCTP2)! MCTP2!c70135_g1_i2! Q63746! NFKB!inhibitor!alpha(Nfkbia)! IKBA!c99299_g1_i2! Q3UMF0! CoblElike!1(Cobll1)! COBL1!c89943_g1_i3! Q3UEG6! alanineEglyoxylate!aminotransferase!2(Agxt2)! AGT2!c80251_g1_i2! Q6AY09! heterogeneous!nuclear!ribonucleoprotein!H2!(H')(Hnrnph2)! HNRH2!c85762_g1_i1! Q8N264! Rho!GTPase!activating!protein!24(ARHGAP24)! RHG24!c96499_g1_i1! Q5TZ80! hook!microtubuleEtethering!protein!1(hook1)! HOOK1!c94380_g1_i1! Q9NRE2! teashirt!zinc!finger!homeobox!2(TSHZ2)! TSH2!c78284_g1_i1! Q96BZ8! leukocyte!receptor!cluster!member!1(LENG1)! LENG1!c81220_g2_i1! Q9YHU0! CEterminal!binding!protein!1!L!homeolog(ctbp1.L)! CTBP1!c86252_g1_i1! Q15080! neutrophil!cytosolic!factor!4(NCF4)! NCF4!c86157_g1_i1! Q7ZZ03! fucose!mutarotase(fuom)! FUCM!c80294_g1_i1! O42364! apolipoprotein!Eb(apoeb)! APOEB!c91338_g1_i2! Q9NQX4! myosin!VC(MYO5C)! MYO5C!c93919_g2_i3! Q4R6I1! gypsy!retrotransposon!integrase!1(GIN1)! GIN1!c94499_g1_i2! Q4LDD4! ArfGAP!with!RhoGAP!domain,!ankyrin!repeat!and!PH!domain!1(Arap1)! ARAP1!c28060_g1_i1! O43150! ArfGAP!with!SH3!domain,!ankyrin!repeat!and!PH!domain!2(ASAP2)! ASAP2!c79805_g1_i1! Q9CRG1! transmembrane!7!superfamily!member!3(Tm7sf3)! TM7S3!c77849_g1_i2! A3KNS9! allEtrans!retinoic!acidEinduced!differentiation!factor(atraid)! ARAID!c92323_g1_i5! P53603! formimidoyltransferase!cyclodeaminase(FTCD)! FTCD!
!
! 105!
c54321_g1_i1! Q5U3Q6! thyroid!hormone!receptor!interactor!10a(trip10a)! CIP4!c96138_g1_i6! O14936! calcium/calmodulin!dependent!serine!protein!kinase(CASK)! CSKP!c95403_g1_i2! Q96T21! SECIS!binding!protein!2(SECISBP2)! SEBP2!c86536_g2_i5! Q8R3S2! tetraspanin!33(Tspan33)! TSN33!c95777_g4_i4! Q13018! phospholipase!A2!receptor!1(PLA2R1)! PLA2R!c87136_g1_i1! O35790! phosphatidylinositol!glycan!anchor!biosynthesis,!class!L(Pigl)! PIGL!
c99278_g1_i2! Q15751!HECT!and!RLD!domain!containing!E3!ubiquitin!protein!ligase!family!member!1(HERC1)! HERC1!
c98310_g1_i2! Q9H1A4! anaphase!promoting!complex!subunit!1(ANAPC1)! APC1!c83934_g1_i1! O43609! sprouty!RTK!signaling!antagonist!1(SPRY1)! SPY1!c97868_g1_i5! Q9Y5B6! PAX3!and!PAX7!binding!protein!1(PAXBP1)! PAXB1!c95572_g1_i2! O75208! coenzyme!Q9(COQ9)! COQ9!c94961_g1_i2! Q8WZA0! leucine!zipper!and!CTNNBIP1!domain!containing(LZIC)! LZIC!c98800_g1_i2! Q3U7R1! extended!synaptotagminElike!protein!1(Esyt1)! ESYT1!c80950_g1_i1! P24928! RNA!polymerase!II!subunit!A(POLR2A)! RPB1!c89977_g1_i4! P61129! zinc!finger!CCCHEtype!containing!6(ZC3H6)! ZC3H6!c92398_g2_i2! Q8N3J5! protein!phosphatase,!Mg2+/Mn2+!dependent!1K(PPM1K)! PPM1K!c84310_g1_i1! Q1LVF0! laminin,!gamma!1(lamc1)! LAMC1!c86877_g1_i1! Q92831! lysine!acetyltransferase!2B(KAT2B)! KAT2B!c68896_g1_i1! Q96AT9! ribuloseE5EphosphateE3Eepimerase(RPE)! RPE!c90214_g1_i1! Q7ZVP8! transmembrane!protein!38B(tmem38b)! TM38B!
!
! 106!
c85243_g2_i1! Q8IW93! Rho!guanine!nucleotide!exchange!factor!19(ARHGEF19)! ARHGJ!c94453_g1_i1! Q6A051! attractin!like!1(Atrnl1)! ATRN1!c84472_g1_i2! A2BID7! PR!domain!containing!10(prdm10)! PRD10!c90391_g2_i9! O00534! von!Willebrand!factor!A!domain!containing!5A(VWA5A)! VMA5A!c93074_g1_i1! Q3T8J9! gonE4!like(GON4L)! GON4L!c80674_g1_i1! P21265! adenylosuccinate!lyase(ADSL)! PUR8!c91258_g1_i4! Q9WTV5! proteasome!26S!subunit,!nonEATPase!9(Psmd9)! PSMD9!c91191_g1_i1! Q66HB3! intraflagellar!transport!80(Ift80)! IFT80!c70498_g1_i1! Q5M8Z0! betaineEEhomocysteine!SEmethyltransferase(bhmt)! BHMT1!c84180_g1_i1! Q9TU34! inositol!1,4,5Etrisphosphate!receptor!type!1(ITPR1)! ITPR1!c93931_g2_i1! Q6NV83! U2!snRNPEassociated!SURP!domain!containing(U2surp)! SR140!c85809_g1_i1! Q8WW59! SPRY!domain!containing!4(SPRYD4)! SPRY4!c91788_g2_i1! A3KP59! zgc:162967(zgc:162967)! NO66!c90538_g1_i1! Q3ULF4! spastic!paraplegia!7!homolog!(human)(Spg7)! SPG7!c99084_g2_i2! Q1LWG4! lysophosphatidylcholine!acyltransferase!1(lpcat1)! PCAT1!c95567_g1_i2! Q6PC40! cell!division!cycle!123!homolog!(S.!cerevisiae)(cdc123)! CD123!c81985_g4_i1! Q15911! zinc!finger!homeobox!3(ZFHX3)! ZFHX3!c67144_g1_i1! Q0P5L5! sulfatase!modifying!factor!1(SUMF1)! SUMF1!c89777_g1_i1! Q2T9T9! FEbox!and!WD!repeat!domain!containing!9(FBXW9)! FBXW9!c86563_g2_i1! Q9ULU4! zinc!finger!MYNDEtype!containing!8(ZMYND8)! PKCB1!c95016_g1_i1! P49754! VPS41,!HOPS!complex!subunit(VPS41)! VPS41!
!
! 107!
c93036_g1_i3! P78524! suppression!of!tumorigenicity!5(ST5)! ST5!c78118_g1_i1! Q6VEU3! partner!of!NOB1!homolog(pno1)! PNO1!c89489_g1_i6! Q9Y2R2! protein!tyrosine!phosphatase,!nonEreceptor!type!22(PTPN22)! PTN22!c88464_g1_i8! Q8K337! inositol!polyphosphateE5Ephosphatase!B(Inpp5b)! I5P2!c92340_g1_i1! Q6NV83! U2!snRNPEassociated!SURP!domain!containing(U2surp)! SR140!c99163_g1_i2! C6FG12! NLR!family!CARD!domain!containing!5(nlrc5)! NLRC5!c96899_g1_i2! A2VDJ0! KIAA0922(KIAA0922)! T131L!c81143_g1_i1! Q8WX92! negative!elongation!factor!complex!member!B(NELFB)! NELFB!c42254_g1_i1! Q90YV7! ribosomal!protein!L11(rpl11)! RL11!c86253_g1_i1! Q96MG7! NSE3!homolog,!SMC5ESMC6!complex!component(NSMCE3)! MAGG1!c89040_g3_i2! O08584! KruppelElike!factor!6(Klf6)! KLF6!c88178_g1_i1! Q6PBQ2! charged!multivesicular!body!protein!7(chmp7)! CHMP7!c98494_g2_i1! Q5U378! tubulin!folding!cofactor!E(tbce)! TBCE!c93027_g2_i1! Q8NA19! l(3)mbtElike!4!(Drosophila)(L3MBTL4)! LMBL4!c81614_g1_i1! Q3UHX9! SPOUT!domain!containing!methyltransferase!1(Spout1)! CI114!c99086_g1_i1! Q99MS7! EH!domain!binding!protein!1Elike!1(Ehbp1l1)! EH1L1!c85575_g1_i2! Q8VE97! serine/arginineErich!splicing!factor!4(Srsf4)! SRSF4!c89067_g1_i1! O95478! NSA2,!ribosome!biogenesis!homolog(NSA2)! NSA2!c93193_g2_i2! Q98TW1! nuclear!receptor!coactivator!2(ncoa2)! NCOA2!c88777_g3_i8! Q5RKN4! glyoxylate!reductase!1!homolog!(Arabidopsis)(glyr1)! GLYR1!c99494_g1_i5! O93530! Werner!syndrome,!RecQ!helicaseElike!L!homeolog(wrn.L)! WRN!
!
! 108!
c88722_g1_i1! Q9BXL7! caspase!recruitment!domain!family!member!11(CARD11)! CAR11!c97468_g1_i2! P38935! immunoglobulin!mu!binding!protein!2(IGHMBP2)! SMBP2!c82142_g1_i1! Q6NWE0! zgc:85789(zgc:85789)! CK054!c85474_g1_i1! O15105! SMAD!family!member!7(SMAD7)! SMAD7!c97392_g2_i3! A7MBI0! protein!kinase!C!and!casein!kinase!substrate!in!neurons!1(PACSIN1)! PACN1!c98999_g1_i2! Q5EY87! grainyheadElike!transcription!factor!1!L!homeolog(grhl1.L)! GRHL1!c97427_g2_i1! A0JMF6! myotubularin!related!protein!10(mtmr10)! MTMRA!c90380_g1_i1! P52483! ubiquitinEconjugating!enzyme!E2E!3(Ube2e3)! UB2E3!c84768_g1_i2! Q98SV1! selenoprotein!P,!plasma,!1a(sepp1a)! SELPA!c92161_g1_i1! Q5F361! TBC1!domain!containing!kinase(TBCK)! TBCK!c92593_g1_i1! P78524! suppression!of!tumorigenicity!5(ST5)! ST5!c98595_g1_i2! O43933! peroxisomal!biogenesis!factor!1(PEX1)! PEX1!
c97334_g1_i1! P31939!5EaminoimidazoleE4Ecarboxamide!ribonucleotide!formyltransferase/IMP!cyclohydrolase(ATIC)! PUR9!
c93041_g1_i2! Q2M2R8! peroxisomal!biogenesis!factor!5(Pex5)! PEX5!c86813_g1_i1! P16330! 2',3'Ecyclic!nucleotide!3'!phosphodiesterase(Cnp)! CN37!c89523_g1_i2! Q13546! receptor!interacting!serine/threonine!kinase!1(RIPK1)! RIPK1!c85867_g1_i3! Q6P963! hydroxyacylglutathione!hydrolase(hagh)! GLO2!c93693_g2_i2! Q5VZK9! capping!protein!regulator!and!myosin!1!linker!1(CARMIL1)! LR16A!c90803_g3_i1! Q4R4H5! TSC22!domain!family!member!1(TSC22D1)! T22D1!c79226_g1_i1! Q1LUI2! HD!domain!containing!2(hddc2)! HDDC2!
!
! 109!
c98917_g1_i2! Q8CHI5! period!circadian!clock!1(Per1)! PER1!c99574_g3_i6! Q9H2F5! enhancer!of!polycomb!homolog!1(EPC1)! EPC1!
c79444_g1_i1! Q9I8K7!Cbp/p300Einteracting!transactivator,!with!Glu/AspErich!carboxyEterminal!domain,!4(CITED4)! CITE3!
c83385_g3_i1! Q9Z329! inositol!1,4,5Etriphosphate!receptor!2(Itpr2)! ITPR2!c91666_g3_i1! O43150! ArfGAP!with!SH3!domain,!ankyrin!repeat!and!PH!domain!2(ASAP2)! ASAP2!c88731_g2_i2! Q9UKA2! FEbox!and!leucine!rich!repeat!protein!4(FBXL4)! FBXL4!
c79974_g2_i4! Q6PFT9!amyloid!beta!(A4)!precursor!proteinEbinding,!family!B,!member!1!interacting!protein(apbb1ip)! AB1IP!
c100065_g3_i1! Q9BZZ2! sialic!acid!binding!Ig!like!lectin!1(SIGLEC1)! SN!c92473_g1_i2! B2RRE4! zinc!finger!protein!518B(Zfp518b)! Z518B!c98408_g1_i1! Q6JQN1! acylECoA!dehydrogenase!family!member!10(ACAD10)! ACD10!c99250_g1_i3! Q5HYK7! SH3!domain!containing!19(SH3D19)! SH319!c98867_g1_i1! Q9R1K8! RAS!guanyl!releasing!protein!1(Rasgrp1)! GRP1!
c95382_g1_i1! Q8VBT9!alveolar!soft!part!sarcoma!chromosome!region,!candidate!1!(human)(Aspscr1)! ASPC1!
c125484_g1_i1! P60868! ribosomal!protein!S20(Rps20)! RS20!c98792_g3_i1! O55047! tousledElike!kinase!2!(Arabidopsis)(Tlk2)! TLK2!c80379_g1_i3! Q8CIS0! caspase!recruitment!domain!family,!member!11(Card11)! CAR11!c97556_g3_i3! Q6P6Y1! zgc:66014(zgc:66014)! K1468!c99021_g4_i1! Q8NBX0! saccharopine!dehydrogenase!(putative)(SCCPDH)! SCPDL!
!
! 110!
c87474_g1_i3! Q80WC3! trinucleotide!repeat!containing!18(Tnrc18)! TNC18!c95634_g1_i1! A2VDJ0! KIAA0922(KIAA0922)! T131L!c68188_g1_i1! O00303! eukaryotic!translation!initiation!factor!3!subunit!F(EIF3F)! EIF3F!c90379_g1_i3! Q8NEM7! SPT20!homolog,!SAGA!complex!component(SUPT20H)! SP20H!c93194_g1_i1! Q5PQM2! kinesin!light!chain!4(Klc4)! KLC4!c140810_g1_i1! P26641! eukaryotic!translation!elongation!factor!1!gamma(EEF1G)! EF1G!c37746_g1_i1! P62845! ribosomal!protein!S15(Rps15)! RS15!c98893_g2_i2! Q5DW34! euchromatic!histone!methyltransferase!1(Ehmt1)! EHMT1!c58806_g1_i1! P62282! ribosomal!protein!S11(Rps11)! RS11!c91615_g1_i1! Q7T3H9! hydroxypyruvate!isomerase(hyi)! HYI!c75051_g1_i6! Q15650! thyroid!hormone!receptor!interactor!4(TRIP4)! TRIP4!c93899_g3_i1! Q5ZLC6! ankyrin!repeat!domain!10(ANKRD10)! ANR10!c90573_g1_i8! Q8R5C8! zinc!finger,!MYND!domain!containing!11(Zmynd11)! ZMY11!c89757_g1_i1! Q803F6! ribosomal!protein!SA(rpsa)! RSSA!c69965_g1_i1! O35054! claudin!4(Cldn4)! CLD4!c93076_g2_i2! Q3ZT31! sorting!nexin!25(Snx25)! SNX25!c96996_g1_i1! Q63356! myosin!IE(Myo1e)! MYO1E!c82470_g1_i5! Q5XK92! KIAA1524!L!homeolog(kiaa1524.L)! CIP2A!c68398_g1_i1! Q7ZTZ2! ribosomal!L24!domain!containing!1(rsl24d1)! RLP24!c90098_g1_i2! Q9JIP4! pannexin!1(Panx1)! PANX1!c83314_g1_i1! Q24JV9! lectin,!galactosideEbinding,!soluble,!3!binding!protein!a(lgals3bpa)! L3BPA!
!
! 111!
c69955_g1_i2! Q8BUV3! gephyrin(Gphn)! GEPH!c32783_g1_i1! Q5ZJ56! ribosomal!protein!L7(RPL7)! RL7!c67850_g1_i1! Q6P2P2! protein!arginine!methyltransferase!9(PRMT9)! ANM10!c77797_g1_i1! Q5RKI9! mitochondrial!ribosome!recycling!factor(Mrrf)! RRFM!c96961_g1_i1! Q8WXH0! spectrin!repeat!containing!nuclear!envelope!protein!2(SYNE2)! SYNE2!c22139_g1_i1! P67985! ribosomal!protein!L22(RPL22)! RL22!c92395_g1_i4! Q05397! protein!tyrosine!kinase!2(PTK2)! FAK1!c79471_g1_i1! Q92934! BCL2!associated!agonist!of!cell!death(BAD)! BAD!c86886_g2_i1! Q80UG5! septin!9(Sept9)! 43352!c73346_g1_i1! P32046! ribosomal!protein!L37a(RPL37A)! RL37A!c92616_g1_i1! Q61036! p21!protein!(Cdc42/Rac)Eactivated!kinase!3(Pak3)! PAK3!c46758_g1_i1! Q9NR30! DExDEbox!helicase!21(DDX21)! DDX21!c68988_g1_i1! Q90Z10! ribosomal!protein!L13(rpl13)! RL13!c94870_g1_i5! Q9UPV9! trafficking!kinesin!protein!1(TRAK1)! TRAK1!c59810_g1_i1! Q6PE25! eukaryotic!translation!elongation!factor!1!gamma(eef1g)! EF1G!c97074_g1_i1! Q9QY06! myosin!IXb(Myo9b)! MYO9B!c94852_g1_i1! Q5S1U6! interferon!related!developmental!regulator!1(IFRD1)! IFRD1!c97805_g1_i1! Q9UJ83! 2EhydroxyacylECoA!lyase!1(HACL1)! HACL1!c89463_g1_i1! Q3USH5! splicing!factor,!suppressor!of!whiteEapricot!homolog!(Drosophila)(Sfswap)! SFSWA!c42061_g1_i1! P69091! ribosomal!protein!L18(rpl18)! RL18!c74582_g1_i2! Q90YQ4! ribosomal!protein!S19(rps19)! RS19!
!
! 112!
c98260_g1_i1! Q4U2R1! HECT!and!RLD!domain!containing!E3!ubiquitin!protein!ligase!2(Herc2)! HERC2!c99042_g1_i1! Q6PHS6! sorting!nexin!13(Snx13)! SNX13!c98152_g1_i3! O15254! acylECoA!oxidase!3,!pristanoyl(ACOX3)! ACOX3!c84213_g1_i2! Q4A1L5! beclin!1(BECN1)! BECN1!c71097_g1_i1! P19804! NME/NM23!nucleoside!diphosphate!kinase!2(Nme2)! NDKB!c56488_g1_i1! P68200! ribosomal!protein!S27a(rps27a)! RS27A!c63212_g1_i2! P62278! ribosomal!protein!S13(Rps13)! RS13!c88104_g1_i2! Q2KIQ4! coenzyme!Q2,!polyprenyltransferase(COQ2)! COQ2!c91937_g2_i1! Q91XF0! pyridoxine!5'Ephosphate!oxidase(Pnpo)! PNPO!c96407_g2_i2! Q9Y222! cyclin!D!binding!myb!like!transcription!factor!1(DMTF1)! DMTF1!c173393_g1_i1! Q90YV0! ribosomal!protein!L18(rpl18)! RL18!
c92791_g1_i2! Q6PGB8!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!a,!member!1(Smarca1)! SMCA1!
c66944_g1_i1! Q98TF7! ribosomal!protein!L35(RPL35)! RL35!c89191_g1_i1! Q96EP0! ring!finger!protein!31(RNF31)! RNF31!c21160_g1_i1! P30050! ribosomal!protein!L12(RPL12)! RL12!c88457_g2_i1! Q8TEW0! parE3!family!cell!polarity!regulator(PARD3)! PARD3!c96405_g1_i1! Q9Z2C4! myotubularin!related!protein!1(Mtmr1)! MTMR1!c79025_g1_i1! Q9YGF2! S6!ribosomal!protein(LOC100135859)! RS6!c96244_g1_i1! Q7ZWD4! UDPENEacetylglucosamine!pyrophosphorylase!1,!like!1(uap1l1)! UAP1L!c98754_g1_i1! B0R0T1! von!Willebrand!factor!A!domain!containing!8(vwa8)! VWA8!
!
! 113!
c75713_g1_i1! Q9UGU5! HMGEbox!containing!4(HMGXB4)! HMGX4!c86798_g1_i3! Q8C1B2! TCDDEinducible!poly(ADPEribose)!polymerase(Tiparp)! PARPT!c76436_g1_i1! P67985! ribosomal!protein!L22(RPL22)! RL22!c97003_g1_i1! Q08890! iduronate!2Esulfatase(Ids)! IDS!c97556_g4_i1! Q6P6Y1! zgc:66014(zgc:66014)! K1468!c56027_g1_i1! Q64152! basic!transcription!factor!3(Btf3)! BTF3!c91395_g1_i1! A2RT67! DENN/MADD!domain!containing!3(Dennd3)! DEND3!c90102_g1_i1! O94901! Sad1!and!UNC84!domain!containing!1(SUN1)! SUN1!c96369_g1_i2! A8WH75! CD302!molecule(CD302)! CD302!c88502_g3_i1! P46778! ribosomal!protein!L21(RPL21)! RL21!c21308_g1_i1! Q0Z8U2! ribosomal!protein!S3(RPS3)! RS3!c88871_g2_i1! Q7SXR3! macrophage!erythroblast!attacher(maea)! MAEA!c53935_g1_i1! Q7ZWJ4! ribosomal!protein!L18a(rpl18a)! RL18A!c21220_g1_i1! P50894! ribosomal!protein!S7(rps7)! RS7!c92812_g3_i1! P97363! serine!palmitoyltransferase,!long!chain!base!subunit!2(Sptlc2)! SPTC2!c97283_g1_i1! O43312! MTSS1,!IEBAR!domain!containing(MTSS1)! MTSS1!c91306_g1_i1! A5D7C9! transmembrane!protein!150C(TMEM150C)! T150C!c59076_g1_i1! P30151! eukaryotic!translation!elongation!factor!1!beta!2!L!homeolog(eef1b2.L)! EF1B!c53828_g1_i1! Q90YV8! ribosomal!protein!L10a(rpl10a)! RL10A!c84949_g1_i1! P63245! receptor!for!activated!C!kinase!1(Rack1)! GBLP!
!
! 114!
c99278_g1_i5! Q15751!HECT!and!RLD!domain!containing!E3!ubiquitin!protein!ligase!family!member!1(HERC1)! HERC1!
c99101_g4_i1! Q8K4L3! supervillin(Svil)! SVIL!c83120_g2_i2! P62264! ribosomal!protein!S14(Rps14)! RS14!c93874_g1_i1! Q04887! SRY!(sex!determining!region!Y)Ebox!9(Sox9)! SOX9!c83636_g1_i1! Q6TNP8! vacuolar!protein!sorting!26!homolog!A!(S.!pombe)(vps26a)! VP26A!c79063_g1_i1! Q90YS3! ribosomal!protein!S2(rps2)! RS2!c83120_g2_i1! P62264! ribosomal!protein!S14(Rps14)! RS14!c55742_g1_i1! Q90YS2! ribosomal!protein!S3(rps3)! RS3!c89085_g1_i1! P49815! tuberous!sclerosis!2(TSC2)! TSC2!c59825_g1_i1! P46782! ribosomal!protein!S5(RPS5)! RS5!c94562_g1_i3! Q08DB5! syntaxin!5(STX5)! STX5!c25534_g1_i1! P41105! ribosomal!protein!L28(Rpl28)! RL28!c63212_g1_i1! P62278! ribosomal!protein!S13(Rps13)! RS13!c88354_g1_i4! Q9ESL4! sterile!alpha!motif!and!leucine!zipper!containing!kinase!AZK(Zak)! MLTK!c85667_g1_i1! Q86XS8! ring!finger!protein!130(RNF130)! GOLI!c80535_g1_i1! Q5U3Q6! thyroid!hormone!receptor!interactor!10a(trip10a)! CIP4!c89298_g1_i1! Q9WVM3! anaphase!promoting!complex!subunit!7(Anapc7)! APC7!c64509_g1_i1! P32969! ribosomal!protein!L9(RPL9)! RL9!c56967_g1_i1! Q90YQ6! 40S!ribosomal!protein!S17(LOC100304569)! RS17!c70675_g1_i1! P62856! ribosomal!protein!S26(Rps26)! RS26!
!
! 115!
c77664_g1_i1! Q503L4! isoamyl!acetateEhydrolyzing!esterase!1!homolog!(S.!cerevisiae)(iah1)! IAH1!c88691_g1_i4! Q86VK4! zinc!finger!protein!410(ZNF410)! ZN410!c76699_g1_i1! Q6P0V6! ribosomal!protein!L8(rpl8)! RL8!c70574_g2_i1! Q60817! nascent!polypeptideEassociated!complex!alpha!polypeptide(Naca)! NACA!c70675_g2_i1! P62856! ribosomal!protein!S26(Rps26)! RS26!c98477_g1_i2! O00567! NOP56!ribonucleoprotein(NOP56)! NOP56!c89692_g1_i6! Q5ZJL7! damage!specific!DNA!binding!protein!2(DDB2)! DDB2!
c71146_g1_i1! P15153!rasErelated!C3!botulinum!toxin!substrate!2!(rho!family,!small!GTP!binding!protein!Rac2)(RAC2)! RAC2!
c71924_g1_i1! P46783! ribosomal!protein!S10(RPS10)! RS10!c95052_g1_i1! Q8TD16! BICD!cargo!adaptor!2(BICD2)! BICD2!c111222_g1_i1! P62246! ribosomal!protein!S15a(Rps15a)! RS15A!c85327_g1_i2! Q8QHJ9! interleukin!17!receptor!D(il17rd)! I17RD!c77244_g1_i1! Q2M2T6! WD!repeat!domain!83!opposite!strand(WDR83OS)! ASTER!c71839_g1_i2! P0C276! ubiquitin!AE52!residue!ribosomal!protein!fusion!product!1(UBA52)! RL40!c74582_g1_i1! Q5R8M9! ribosomal!protein!S19(RPS19)! RS19!c82615_g2_i1! P27659! ribosomal!protein!L3(Rpl3)! RL3!c42106_g1_i1! A1XQU3! ribosomal!protein!L14(RPL14)! RL14!c100032_g1_i1! P07722! myelinEassociated!glycoprotein(Mag)! MAG!c91089_g1_i1! Q99583! MAX!network!transcriptional!repressor(MNT)! MNT!c100006_g2_i1! O57415! ras!responsive!element!binding!protein!1(RREB1)! RREB1!
!
! 116!
c144497_g1_i1! P68200! ribosomal!protein!S27a(rps27a)! RS27A!c25528_g1_i1! P46405! ribosomal!protein!S12(RPS12)! RS12!c90204_g2_i2! Q9D9B4! RIKEN!cDNA!1700112E06!gene(1700112E06Rik)! CJ011!c53987_g1_i1! P62243! ribosomal!protein!S8(Rps8)! RS8!c37989_g1_i1! Q8JGS9! ribosomal!protein!S18(rps18)! RS18!c88199_g1_i6! Q8BHY8! sorting!nexin!14(Snx14)! SNX14!c19607_g1_i1! Q90YS0! ribosomal!protein!S4,!XElinked(rps4x)! RS4!c12590_g1_i1! Q8JGS9! ribosomal!protein!S18(rps18)! RS18!c89016_g1_i1! Q02874! H2A!histone!family,!member!Y(H2afy)! H2AY!c94283_g1_i1! Q6DI40! tetratricopeptide!repeat!domain!33(ttc33)! TTC33!c74533_g3_i1! Q64152! basic!transcription!factor!3(Btf3)! BTF3!c125485_g1_i1! Q90YU1! ribosomal!protein!L27(rpl27)! RL27!c98742_g1_i1! Q1RLX4! trafficking!protein!particle!complex!11(trappc11)! TPC11!c55749_g1_i1! P62832! ribosomal!protein!L23(Rpl23)! RL23!c21475_g1_i1! P08736! Elongation!factor!1alpha48D(Ef1alpha48D)! EF1A1!c94538_g2_i3! Q3UCV8! OTU!deubiquitinase!with!linear!linkage!specificity(Otulin)! F105B!c87845_g1_i1! Q3UU96! CDC42!binding!protein!kinase!alpha(Cdc42bpa)! MRCKA!c54008_g1_i1! Q56K03! ribosomal!protein!L27a(RPL27A)! RL27A!c76176_g2_i1! Q2KJ36! dual!specificity!phosphatase!6(DUSP6)! DUS6!c91720_g1_i2! Q5E9R2! 1EacylglycerolE3Ephosphate!OEacyltransferase!4(AGPAT4)! PLCD!
!
! 117!
c89009_g1_i1! Q7ZVK3!sirtuin!2!(silent!mating!type!information!regulation!2,!homolog)!2!(S.!cerevisiae)(sirt2)! SIR2!
c97792_g1_i6! Q8TAF3! WD!repeat!domain!48(WDR48)! WDR48!c31345_g1_i1! P18660! ribosomal!protein,!large,!P1(RPLP1)! RLA1!c96729_g2_i3! Q9Y4D1! dishevelled!associated!activator!of!morphogenesis!1(DAAM1)! DAAM1!c76037_g1_i1! B5RI54! eukaryotic!translation!initiation!factor!3!subunit!HElike(LOC100196680)! EIF3H!c98936_g1_i1! Q68CZ2! tensin!3(TNS3)! TENS3!c77728_g1_i1! Q02878! ribosomal!protein!L6(RPL6)! RL6!c100111_g1_i1! P49207! ribosomal!protein!L34(RPL34)! RL34!c98466_g3_i1! Q9BZF9! uveal!autoantigen!with!coiledEcoil!domains!and!ankyrin!repeats(UACA)! UACA!c70535_g1_i1! B5DGL6! 40S!ribosomal!protein!S3a(rs3a)! RS3A!c98448_g1_i2! Q5R7F5! semaphorin!6D(SEMA6D)! SEM6D!c59805_g1_i1! P24049! ribosomal!protein!L17(Rpl17)! RL17!c88136_g1_i2! P63329! protein!phosphatase!3!catalytic!subunit!alpha(Ppp3ca)! PP2BA!
c92241_g2_i2! Q0P4K8!nuclear!factor!of!activated!TEcells,!cytoplasmic,!calcineurinEdependent!2!interacting!protein(nfatc2ip)! NF2IP!
c82679_g1_i2! Q17QQ5! G!proteinEcoupled!receptor!137(GPR137)! G137A!c93773_g1_i1! Q6DEJ6! major!facilitator!superfamily!domain!containing!2ab(mfsd2ab)! MF2AB!c91365_g1_i3! Q96IP4! family!with!sequence!similarity!46!member!A(FAM46A)! FA46A!c98949_g1_i1! Q7T037! ring!finger!protein,!LIM!domain!interacting!S!homeolog(rlim.S)! RF12B!c98590_g2_i1! Q9QX47! Son!DNA!binding!protein(Son)! SON!
!
! 118!
c96436_g1_i6! Q9NWH9! SAFB!like!transcription!modulator(SLTM)! SLTM!c85127_g1_i1! P00637! fructoseEbisphosphatase!1(FBP1)! F16P1!c99075_g2_i1! P84104! serine/arginineErich!splicing!factor!3(Srsf3)! SRSF3!c92397_g1_i2! P70404! isocitrate!dehydrogenase!3!(NAD+),!gamma(Idh3g)! IDHG1!c54758_g1_i1! Q9BZE4! GTP!binding!protein!4(GTPBP4)! NOG1!c99539_g1_i1! Q96JG6! VPS50,!EARP/GARPII!complex!subunit(VPS50)! CC132!c94338_g1_i2! Q8NF50! dedicator!of!cytokinesis!8(DOCK8)! DOCK8!c96966_g2_i1! Q9UJS0! solute!carrier!family!25!member!13(SLC25A13)! CMC2!c38545_g1_i1! Q9H1C4! uncE93!homolog!B1!(C.!elegans)(UNC93B1)! UN93B!c63991_g1_i1! Q9WV25! polyEU!binding!splicing!factor!60(Puf60)! PUF60!c96569_g2_i2! Q7TSH2! phosphorylase!kinase!beta(Phkb)! KPBB!c100036_g1_i2! Q68CJ6! nuclear!GTPase,!germinal!center!associated(NUGGC)! SLIP!c97879_g1_i2! Q9UGQ2! calcium!channel!flower!domain!containing!1(CACFD1)! FLOWR!c100037_g1_i1! A0JMF6! myotubularin!related!protein!10(mtmr10)! MTMRA!c94207_g1_i1! Q3SYZ4! aspartylEtRNA!synthetase(DARS)! SYDC!c99842_g1_i4! Q96JC1! VPS39,!HOPS!complex!subunit(VPS39)! VPS39!c99826_g1_i1! O35161! cadherin,!EGF!LAG!sevenEpass!GEtype!receptor!1(Celsr1)! CELR1!c69057_g1_i1! Q6DRC4! eukaryotic!translation!initiation!factor!3,!subunit!G(eif3g)! EIF3G!c56583_g1_i1! P05303! Elongation!factor!1alpha100E(Ef1alpha100E)! EF1A2!c99869_g1_i2! Q9JLN9! mechanistic!target!of!rapamycin!(serine/threonine!kinase)(Mtor)! MTOR!c95689_g1_i1! Q12774! Rho!guanine!nucleotide!exchange!factor!5(ARHGEF5)! ARHG5!
!
! 119!
Supplementary Table 2 Commonly downregulated DEG from transcriptome analysis
Transcript*Read*ID* Uniprot*ID* Unigene*name*from*DAVID* * Gene*Symbol*c89105_g1_i2! P56745! claudin!1(Cldn1)! CLD1!c93854_g1_i3! Q95218! deleted!in!malignant!brain!tumors!1(DMBT1)! DMBT1!c88303_g1_i2! Q92611! ER!degradation!enhancing!alphaEmannosidase!like!protein!1(EDEM1)! EDEM1!c86451_g1_i3! P35615! eukaryotic!translation!termination!factor!1!S!homeolog(etf1.S)! ERF1!c99751_g1_i5! Q86VS8! hook!microtubule!tethering!protein!3(HOOK3)! HOOK3!c89465_g2_i2! Q86UA1! preEmRNA!processing!factor!39(PRPF39)! PRP39!c92812_g3_i5! P97363! serine!palmitoyltransferase,!long!chain!base!subunit!2(Sptlc2)! SPTC2!c85304_g2_i3! P58929! glucocorticoid!modulatory!element!binding!protein!2(Gmeb2)! GMEB2!c93591_g2_i7! Q7ZUC2! stromal!cell!derived!factor!4(sdf4)! CAB45!c94688_g1_i2! Q9BTE7! defective!in!cullin!neddylation!1!domain!containing!5(DCUN1D5)! DCNL5!c97099_g3_i6! Q9H2J7! solute!carrier!family!6!member!15(SLC6A15)! S6A15!c92448_g3_i2! O94913! PCF11!cleavage!and!polyadenylation!factor!subunit(PCF11)! PCF11!c96922_g1_i1! P97363! serine!palmitoyltransferase,!long!chain!base!subunit!2(Sptlc2)! SPTC2!c97455_g2_i6! Q99743! neuronal!PAS!domain!protein!2(NPAS2)! NPAS2!c82756_g1_i6! Q8K585! high!mobility!group!ATEhook!1(Hmga1)! HMGA1!c93555_g1_i1! Q28D01! WD!repeat!domain!26(wdr26)! WDR26!c91865_g1_i3! Q8MKF1! thiamine!triphosphatase(THTPA)! THTPA!c78885_g2_i2! Q9NQG5! regulation!of!nuclear!preEmRNA!domain!containing!1B(RPRD1B)! RPR1B!
!
! 120!
c81140_g1_i4! Q8R087!xylosylprotein!beta1,4Egalactosyltransferase,!polypeptide!7!(galactosyltransferase!I)(B4galt7)! B4GT7!
c98467_g1_i2! Q9Y376! calcium!binding!protein!39(CAB39)! CAB39!c97620_g2_i5! O60583! cyclin!T2(CCNT2)! CCNT2!c76471_g1_i1! Q568I2! alkaline!ceramidase!1(acer1)! ACER1!c82756_g1_i1! Q8K585! high!mobility!group!ATEhook!1(Hmga1)! HMGA1!c81949_g1_i1! O76082! solute!carrier!family!22!member!5(SLC22A5)! S22A5!c71714_g1_i2! P32320! cytidine!deaminase(CDA)! CDD!c87845_g3_i5! Q0II48! BCL2!like!15(BCL2L15)! B2L15!c93005_g3_i3! Q7SZE5! Sec23!homolog!A,!COPII!coat!complex!component(sec23a)! SC23A!c93352_g1_i1! Q99727! TIMP!metallopeptidase!inhibitor!4(TIMP4)! TIMP4!c84959_g1_i2! Q9JMC3! DnaJ!heat!shock!protein!family!(Hsp40)!member!A4(Dnaja4)! DNJA4!c128378_g1_i1! F1MN90! cell!death!inducing!DFFA!like!effector!c(CIDEC)! CIDEC!c83027_g1_i3! Q6R5N8! tollElike!receptor!13(Tlr13)! TLR13!c97107_g2_i7! O60447! ecotropic!viral!integration!site!5(EVI5)! EVI5!c92954_g1_i1! P31213! steroid!5!alphaEreductase!2(SRD5A2)! S5A2!c93432_g1_i3! P06909! complement!component!factor!h(Cfh)! CFAH!c94562_g1_i5! Q08DB5! syntaxin!5(STX5)! STX5!c84618_g1_i2! Q2KI97! G!proteinEcoupled!receptor!84(GPR84)! GPR84!c74665_g1_i1! P48759! pentraxin!related!gene(Ptx3)! PTX3!c86958_g1_i2! Q99731! CEC!motif!chemokine!ligand!19(CCL19)! CCL19!
!
! 121!
c91801_g1_i2! Q7ZXY0! inositolE3Ephosphate!synthase!1!S!homeolog(isyna1.S)! INO1A!c87845_g3_i1! Q0II48! BCL2!like!15(BCL2L15)! B2L15!c96566_g2_i1! Q01650! solute!carrier!family!7!member!5(SLC7A5)! LAT1!c95086_g1_i4! Q5HZE0! solute!carrier!family!25!member!29(Slc25a29)! MCATL!c63324_g1_i1! Q8CI15! sphingosine!kinase!1(Sphk1)! SPHK1!c98802_g1_i3! A0JND4! strawberry!notch!homolog!2(SBNO2)! SBNO2!c92861_g1_i1! Q9CW07! protein!phosphatase!1,!regulatory!(inhibitor)!subunit!3G(Ppp1r3g)! PP13G!c73218_g1_i2! Q7ZUH1! zgc:56576(zgc:56576)! CN166!c55755_g1_i1! Q804S6! empty!spiracles!homeobox!1(emx1)! EMX1!c102597_g1_i1! Q9BXB5! oxysterol!binding!protein!like!10(OSBPL10)! OSB10!c78889_g1_i2! Q9DA37! sterile!alpha!motif!domain!containing!8(Samd8)! SAMD8!c94252_g1_i2! Q02248! catenin!(cadherin!associated!protein),!beta!1(Ctnnb1)! CTNB1!c94602_g1_i1! Q8WV99! zinc!finger!AN1Etype!containing!2B(ZFAND2B)! ZFN2B!c87718_g1_i4! Q90678! phospholipase!A2!group!VII(PLA2G7)! PAFA!c99644_g1_i2! O88904! homeodomain!interacting!protein!kinase!1(Hipk1)! HIPK1!c99978_g1_i1! Q07617! sperm!associated!antigen!1(SPAG1)! SPAG1!c98185_g1_i2! Q05910! a!disintegrin!and!metallopeptidase!domain!8(Adam8)! ADAM8!c90818_g1_i1! Q5ZLK4! globoside!alphaE1,3ENEacetylgalactosaminyltransferase!1(GBGT1)! GBGT1!c80472_g1_i5! Q9D6N5! Dr1!associated!protein!1!(negative!cofactor!2!alpha)(Drap1)! NC2A!c91801_g1_i3! Q7ZXY0! inositolE3Ephosphate!synthase!1!S!homeolog(isyna1.S)! INO1A!c96935_g1_i1! Q8BNW9! kelch!repeat!and!BTB!(POZ)!domain!containing!11(Kbtbd11)! KBTBB!
!
! 122!
c75532_g2_i2! P51145! FOS!like!2,!APE1!transcription!factor!subunit(Fosl2)! FOSL2!c96481_g1_i1! A5PJN2! endoplasmic!reticulum!oxidoreductase!1!alpha(ERO1A)! ERO1A!c87345_g1_i1! Q5TAA0! tetratricopeptide!repeat!domain!22(TTC22)! TTC22!c93092_g1_i1! P13563! hyaluronan!synthase!1!L!homeolog(has1.L)! HAS1!c100832_g1_i1! O35054! claudin!4(Cldn4)! CLD4!c97810_g3_i1! Q96K37! solute!carrier!family!35!member!E1(SLC35E1)! S35E1!c97567_g2_i1! O94808! glutamineEfructoseE6Ephosphate!transaminase!2(GFPT2)! GFPT2!c78565_g2_i2! Q8IVL1! neuron!navigator!2(NAV2)! NAV2!c92448_g3_i6! O94913! PCF11!cleavage!and!polyadenylation!factor!subunit(PCF11)! PCF11!c96117_g1_i1! Q8TEK3! DOT1!like!histone!lysine!methyltransferase(DOT1L)! DOT1L!c94113_g1_i1! A8HAL1! ubiquitin!specific!peptidase!16(usp16)! UBP16!c80963_g1_i1! A4QNR8! leukocyte!receptor!cluster!(LRC)!member!8(leng8)! LENG8!c95517_g2_i4! P40240! CD9!antigen(Cd9)! CD9!c80253_g2_i1! P59383! leucine!rich!repeat!neuronal!4(Lrrn4)! LRRN4!
c100114_g1_i1! Q8NFL0!UDPEGlcNAc:betaGal!betaE1,3ENEacetylglucosaminyltransferase!7(B3GNT7)! B3GN7!
c84742_g1_i1! Q5M880! PQ!loop!repeat!containing!1(Pqlc1)! PQLC1!c91655_g1_i1! Q61190! interleukin!10!receptor,!beta(Il10rb)! I10R2!c96467_g1_i4! Q6PHK6! purineErich!element!binding!protein!Bb(purbb)! PURB!c89717_g1_i4! Q8R1G6! PDZ!and!LIM!domain!2(Pdlim2)! PDLI2!c91570_g1_i1! Q10835! matrix!metallopeptidase!13!(collagenase!3)!like!L!homeolog(mmp13l.L)! MMP13!
!
! 123!
c87392_g1_i1! P55086! coagulation!factor!II!(thrombin)!receptorElike!1(F2rl1)! PAR2!
c81989_g1_i2! P48597!eukaryotic!translation!initiation!factor!4E!family!member!1B!S!homeolog(eif4e1b.S)! IF4E!
c91339_g2_i2! O35345! karyopherin!(importin)!alpha!6(Kpna6)! IMA7!c93555_g1_i3! Q8C6G8! WD!repeat!domain!26(Wdr26)! WDR26!c88246_g3_i3! Q60769! tumor!necrosis!factor,!alphaEinduced!protein!3(Tnfaip3)! TNAP3!c83545_g1_i1! Q4V7A8! abhydrolase!domain!containing!18(Abhd18)! CD029!c98587_g1_i1! Q9Z1Z3! epsin!2(Epn2)! EPN2!c93659_g2_i1! O60885! bromodomain!containing!4(BRD4)! BRD4!c94404_g1_i1! P97864! caspase!7(Casp7)! CASP7!c92698_g2_i1! Q9DBU0! transmembrane!9!superfamily!member!1(Tm9sf1)! TM9S1!c83252_g1_i2! Q503P5! major!facilitator!superfamily!domain!containing!7(mfsd7)! MFSD7!c85591_g4_i1! Q20A00! DNAEdamageEinducible!transcript!4Elike(ddit4l)! DDT4L!c92306_g2_i3! Q90617! lysosomalEassociated!membrane!protein!2(LAMP2)! LAMP2!c93566_g1_i1! Q96RE7! nucleus!accumbens!associated!1(NACC1)! NACC1!c88303_g1_i4! Q925U4! ER!degradation!enhancer,!mannosidase!alphaElike!1(Edem1)! EDEM1!c68438_g1_i2! Q9JMC3! DnaJ!heat!shock!protein!family!(Hsp40)!member!A4(Dnaja4)! DNJA4!c84876_g2_i1! Q63768! CRK!protoEoncogene,!adaptor!protein(Crk)! CRK!c95905_g3_i2! A0AAS4! sphingomyelin!synthase!1(SGMS1)! SMS1!c96703_g1_i1! Q66HD0! heat!shock!protein!90!beta!family!member!1(Hsp90b1)! ENPL!c86117_g1_i2! P20003! fibroblast!growth!factor!2(FGF2)! FGF2!
!
! 124!
c57042_g1_i2! Q2WED0! C3a!anaphylatoxin!chemotactic!receptor(c3ar1)! C3AR!c91673_g2_i3! Q9TR36! phosphatidylinositol!transfer!protein!beta(PITPNB)! PIPNB!c92954_g1_i2! P31213! steroid!5!alphaEreductase!2(SRD5A2)! S5A2!c28600_g1_i1! Q8IUC6! toll!like!receptor!adaptor!molecule!1(TICAM1)! TCAM1!c92296_g1_i2! Q9WVP1! adaptor!protein!complex!APE1,!mu!2!subunit(Ap1m2)! AP1M2!c82198_g1_i1! Q4R5P1! RAB8A,!member!RAS!oncogene!family(RAB8A)! RAB8A!
c68432_g1_i1! Q287T7!solute!carrier!family!25!(mitochondrial!iron!transporter),!member!37(slc25a37)! MFRN1!
c92720_g1_i3! P61967! adaptor!protein!complex!APE1,!sigma!1(Ap1s1)! AP1S1!c55463_g1_i1! P87378! vEcrk!avian!sarcoma!virus!CT10!oncogene!homolog!L!homeolog(crk.L)! CRK!c85594_g1_i1! P55145! mesencephalic!astrocyte!derived!neurotrophic!factor(MANF)! MANF!c99002_g1_i5! Q8NCJ5! SPRY!domain!containing!3(SPRYD3)! SPRY3!c83252_g1_i5! Q6P3R2! major!facilitator!superfamily!domain!containing!7(mfsd7)! MFS7B!c95896_g2_i1! O94827! pleckstrin!homology!and!RhoGEF!domain!containing!G5(PLEKHG5)! PKHG5!c92218_g1_i9! Q5SPB1! solute!carrier!family!38,!member!2(slc38a2)! S38A2!c93620_g1_i1! P58801! receptor!(TNFRSF)Einteracting!serineEthreonine!kinase!2(Ripk2)! RIPK2!c41178_g1_i1! Q9HD67! myosin!X(MYO10)! MYO10!c93160_g1_i2! Q863Z5! interleukin!4!receptor(IL4R)! IL4RA!c85434_g1_i3! Q8K339! Kin17!DNA!and!RNA!binding!protein(Kin)! KIN17!c73903_g1_i1! P21566! cofilin!2!(muscle)(CFL2)! COF2!c88394_g1_i10! Q5R8D0! UDPEgalactoseE4Eepimerase(GALE)! GALE!
!
! 125!
c96390_g1_i1! P15920! ATPase,!H+!transporting,!lysosomal!V0!subunit!A2(Atp6v0a2)! VPP2!c86667_g1_i1! Q6P950! protein!phosphatase!1,!regulatory!subunit!3Cb(ppp1r3cb)! PR3CB!c94781_g1_i2! A1L3F5! cEMaf!inducing!protein!L!homeolog(cmip.L)! CMIP!c98134_g2_i1! Q0VCH8! transmembrane!protein!65(TMEM65)! TMM65!c43731_g1_i1! O94919! endonuclease!domain!containing!1(ENDOD1)! ENDD1!c84639_g1_i1! Q7TSN4! phosphatidylinositol!glycan!anchor!biosynthesis,!class!W(Pigw)! PIGW!c96865_g1_i1! A2A4P0! DEAH!(AspEGluEAlaEHis)!box!polypeptide!8(Dhx8)! DHX8!c79775_g2_i1! Q5RAS6! solute!carrier!family!31!member!1(SLC31A1)! COPT1!c84609_g1_i2! Q6NYB7! RAB1A,!member!RAS!oncogene!family(Rab1a)! RAB1A!c89518_g2_i4! Q5ZHP7! ELL!associated!factor!2(EAF2)! EAF2!c87209_g1_i2! Q15599! SLC9A3!regulator!2(SLC9A3R2)! NHRF2!c88246_g1_i2! Q60769! tumor!necrosis!factor,!alphaEinduced!protein!3(Tnfaip3)! TNAP3!c87547_g1_i2! D3ZUQ0! Rab!interacting!lysosomal!proteinElike!1(Rilpl1)! RIPL1!c96293_g1_i1! P34932! heat!shock!protein!family!A!(Hsp70)!member!4(HSPA4)! HSP74!c37357_g1_i1! O94919! endonuclease!domain!containing!1(ENDOD1)! ENDD1!c84207_g1_i1! Q0P5H5! regulator!of!GEprotein!signaling!2,!24kDa(RGS2)! RGS2!c88394_g1_i2! Q5R8D0! UDPEgalactoseE4Eepimerase(GALE)! GALE!c89299_g1_i1! Q14435! polypeptide!NEacetylgalactosaminyltransferase!3(GALNT3)! GALT3!c96703_g1_i3! Q66HD0! heat!shock!protein!90!beta!family!member!1(Hsp90b1)! ENPL!c93876_g1_i2! Q9EQP2! EHEdomain!containing!4(Ehd4)! EHD4!c81575_g1_i2! Q969W9! prostate!transmembrane!protein,!androgen!induced!1(PMEPA1)! PMEPA!
!
! 126!
c84291_g1_i1! Q6DED0! translocation!associated!membrane!protein!1!L!homeolog(tram1.L)! TR1L1!c89782_g1_i2! P21860! erbEb2!receptor!tyrosine!kinase!3(ERBB3)! ERBB3!c94123_g2_i3! Q7ZUW2! hypoxia!upEregulated!1(hyou1)! HYOU1!c95688_g1_i1! Q6P4M5! glucoseEfructose!oxidoreductase!domain!containing!1(gfod1)! GFOD1!c98501_g3_i1! P11607! ATPase!sarcoplasmic/endoplasmic!reticulum!Ca2+!transporting!2(ATP2A2)! AT2A2!c90141_g4_i1! P15920! ATPase,!H+!transporting,!lysosomal!V0!subunit!A2(Atp6v0a2)! VPP2!c98963_g1_i4! Q08334! interleukin!10!receptor!subunit!beta(IL10RB)! I10R2!c89299_g1_i2! Q14435! polypeptide!NEacetylgalactosaminyltransferase!3(GALNT3)! GALT3!c88071_g2_i1! P20647! ATPase!sarcoplasmic/endoplasmic!reticulum!Ca2+!transporting!2(ATP2A2)! AT2A2!c98969_g2_i3! Q08CX2! SH2!domain!containing!4A(sh2d4a)! SH24A!c83774_g2_i2! Q99LQ7! transmembrane!protein!189(Tmem189)! TM189!c94537_g4_i1! P52624! uridine!phosphorylase!1(Upp1)! UPP1!c81425_g1_i1! Q8BFQ3! G!proteinEcoupled!receptor!68(Gpr68)! OGR1!c92723_g1_i2! Q6AXM5! choline/ethanolamine!phosphotransferase!1(Cept1)! CEPT1!c95836_g1_i7! Q8BQQ1! zinc!finger,!DHHC!domain!containing!14(Zdhhc14)! ZDH14!c91419_g1_i2! Q7T3F7! cysteine!and!histidineErich!domain!(CHORD)!containing!1b(chordc1b)! CHRD1!c89076_g1_i1! Q5U9X3! G!proteinEcoupled!receptor,!class!C,!group!6,!member!A(gprc6a)! GPC6A!c87058_g1_i1! Q08CK1! ECSIT!signalling!integrator(ecsit)! ECSIT!c77127_g1_i1! Q8CF97! valosin!containing!protein!interacting!protein!1(Vcpip1)! VCIP1!c77750_g1_i2! Q0KL02! triple!functional!domain!(PTPRF!interacting)(Trio)! TRIO!c96620_g1_i1! P33151! cadherin!5(CDH5)! CADH5!
!
! 127!
c88071_g2_i2! Q03669! ATPase,!Ca++!transporting,!cardiac!muscle,!slow!twitch!2(ATP2A2)! AT2A2!c97001_g1_i1! Q9Y487! ATPase!H+!transporting!V0!subunit!a2(ATP6V0A2)! VPP2!c90769_g2_i5! Q8TE68! EPS8!like!1(EPS8L1)! ES8L1!c92930_g1_i1! Q3UPL0! Sec31!homolog!A!(S.!cerevisiae)(Sec31a)! SC31A!c91339_g3_i2! Q503E9! karyopherin!alpha!5!(importin!alpha!6)(kpna5)! IMA5!c82110_g1_i1! Q6P3L6! hydroxysteroid!(17Ebeta)!dehydrogenase!12a(hsd17b12a)! DH12A!c98591_g1_i1! P14625! heat!shock!protein!90!beta!family!member!1(HSP90B1)! ENPL!c87019_g1_i1! Q6DBU5! GDPEmannose!pyrophosphorylase!B(gmppb)! GMPPB!c86670_g1_i1! O60293! zinc!finger!C3H1Etype!containing(ZFC3H1)! ZC3H1!c98431_g1_i4! O60293! zinc!finger!C3H1Etype!containing(ZFC3H1)! ZC3H1!c84776_g2_i1! Q8BUH7! ring!finger!protein!26(Rnf26)! RNF26!c89231_g1_i1! Q58DF3! TraB!domain!containing(TRABD)! TRABD!c92282_g4_i2! P51817! protein!kinase,!XElinked(PRKX)! PRKX!c86633_g1_i3! P62997! transformer!2!beta!homolog!(Drosophila)(Tra2b)! TRA2B!c95613_g2_i1! Q92544! transmembrane!9!superfamily!member!4(TM9SF4)! TM9S4!c87250_g1_i2! O95394! phosphoglucomutase!3(PGM3)! AGM1!c88801_g1_i1! Q803M0! protein!phosphatase!1,!regulatory!subunit!3B(ppp1r3b)! PPR3B!c92306_g2_i1! Q90617! lysosomalEassociated!membrane!protein!2(LAMP2)! LAMP2!c71176_g1_i1! Q6DHR8! NUS1!dehydrodolichyl!diphosphate!synthase!subunit(nus1)! NGBR!c67784_g2_i1! P61208! ADPEribosylation!factorElike!4C(Arl4c)! ARL4C!c87939_g1_i3! P26990! ADP!ribosylation!factor!6(ARF6)! ARF6!
!
! 128!
c82198_g3_i1! Q4R5P1! RAB8A,!member!RAS!oncogene!family(RAB8A)! RAB8A!c94504_g2_i1! Q922R8! protein!disulfide!isomerase!associated!6(Pdia6)! PDIA6!c72455_g1_i1! Q6NZW8! ADPEribosylation!factorElike!8Ba(arl8ba)! AR8BA!c75988_g1_i1! A0JNC2! R3H!domain!containing!2(R3HDM2)! R3HD2!c94562_g1_i1! Q08DB5! syntaxin!5(STX5)! STX5!c98440_g1_i1! Q05718! insulin!like!growth!factor!binding!protein!6(IGFBP6)! IBP6!c87030_g1_i3! Q5U316! RAB35,!member!RAS!oncogene!family(Rab35)! RAB35!c95272_g2_i1! Q14697! glucosidase!II!alpha!subunit(GANAB)! GANAB!c84959_g1_i3! Q9JMC3! DnaJ!heat!shock!protein!family!(Hsp40)!member!A4(Dnaja4)! DNJA4!c91653_g1_i1! Q6P4P2! LMBR1!domain!containing!2b(lmbrd2b)! LMD2B!c88482_g2_i4! P49427! cell!division!cycle!34(CDC34)! UB2R1!c87808_g1_i4! O00154! acylECoA!thioesterase!7(ACOT7)! BACH!c92720_g1_i4! P61967! adaptor!protein!complex!APE1,!sigma!1(Ap1s1)! AP1S1!c97422_g1_i1! P00170! cytochrome!b5!type!A!(microsomal)(CYB5A)! CYB5!c79172_g1_i3! Q9Y2B0! canopy!FGF!signaling!regulator!2(CNPY2)! CNPY2!c92489_g2_i1! Q64516! glycerol!kinase(Gk)! GLPK!c96236_g1_i1! Q8K268! ATPEbinding!cassette,!subEfamily!F!(GCN20),!member!3(Abcf3)! ABCF3!c96684_g1_i2! Q28FJ2! ankyrin!repeat!domain!37(ankrd37)! ANR37!c90692_g1_i2! Q9Y4C4! malignant!fibrous!histiocytoma!amplified!sequence!1(MFHAS1)! MFHA1!c94342_g1_i4! Q32L27! ubiquitin!conjugating!enzyme!E2!Q2(UBE2Q2)! UB2Q2!c92889_g2_i6! Q3THS6! methionine!adenosyltransferase!II,!alpha(Mat2a)! METK2!
!
! 129!
c95524_g3_i6! P11387! topoisomerase!(DNA)!I(TOP1)! TOP1!c98747_g1_i2! Q1RMR2! small!nuclear!ribonucleoprotein!U1!subunit!70(SNRNP70)! RU17!c79251_g1_i1! Q9Z2G0! feminization!1!homolog!b!(C.!elegans)(Fem1b)! FEM1B!c89465_g2_i1! Q1JPZ7! PRP39!preEmRNA!processing!factor!39!homolog!(yeast)(prpf39)! PRP39!c73127_g1_i1! Q14582! MAX!dimerization!protein!4(MXD4)! MAD4!c95802_g1_i3! B0JZG0! solute!carrier!family!23!(ascorbic!acid!transporter),!member!2(slc23a2)! S23A2!c95918_g1_i1! Q96KS0! eglE9!family!hypoxia!inducible!factor!2(EGLN2)! EGLN2!c55797_g1_i1! Q7Z417! NUFIP2,!FMR1!interacting!protein!2(NUFIP2)! NUFP2!
c92874_g1_i2! Q9JMK0!UDPEGal:betaGlcNAc!beta!1,4Egalactosyltransferase,!polypeptide!5(B4galt5)! B4GT5!
c86435_g1_i2! Q9DBG7! signal!recognition!particle!receptor!('docking!protein')(Srpr)! SRPR!c81080_g2_i3! Q640A2! heterogeneous!nuclear!ribonucleoprotein!D!like(hnrnpdl)! HNRDL!c96467_g1_i3! Q6PHK6! purineErich!element!binding!protein!Bb(purbb)! PURB!c90912_g1_i1! O60504! sorbin!and!SH3!domain!containing!3(SORBS3)! VINEX!c92824_g1_i1! A5D9C6! MAF1!homolog,!negative!regulator!of!RNA!polymerase!III(MAF1)! MAF1!c90769_g2_i7! Q8TE68! EPS8!like!1(EPS8L1)! ES8L1!c83252_g1_i1! Q503P5! major!facilitator!superfamily!domain!containing!7(mfsd7)! MFSD7!c115274_g1_i1! Q5ZM55! femE1!homolog!b!(C.!elegans)(FEM1B)! FEM1B!c85398_g2_i1! Q7ZUX6! deoxyhypusine!hydroxylase/monooxygenase(dohh)! DOHH!c99192_g1_i1! Q96PU4! ubiquitin!like!with!PHD!and!ring!finger!domains!2(UHRF2)! UHRF2!c94957_g3_i1! Q9Y2H0! DLG!associated!protein!4(DLGAP4)! DLGP4!
!
! 130!
c84837_g1_i1! O95628! CCR4ENOT!transcription!complex!subunit!4(CNOT4)! CNOT4!c88641_g3_i2! O43670! zinc!finger!protein!207(ZNF207)! ZN207!c98467_g1_i3! Q9Y376! calcium!binding!protein!39(CAB39)! CAB39!c92910_g3_i4! Q32LC7! G3BP!stress!granule!assembly!factor!1(G3BP1)! G3BP1!c88787_g1_i1! Q8TDS4! hydroxycarboxylic!acid!receptor!2(HCAR2)! HCAR2!c91899_g2_i2! Q8IVL1! neuron!navigator!2(NAV2)! NAV2!c84230_g1_i1! Q8TAD8! Smad!nuclear!interacting!protein!1(SNIP1)! SNIP1!c91058_g3_i3! P46060! Ran!GTPase!activating!protein!1(RANGAP1)! RAGP1!c99590_g1_i2! P20650! protein!phosphatase,!Mg2+/Mn2+!dependent,!1A(Ppm1a)! PPM1A!c98989_g1_i1! Q06274! integrin!subunit!alpha!5!L!homeolog(itga5.L)! ITA5!c95951_g1_i1! Q96I24! far!upstream!element!binding!protein!3(FUBP3)! FUBP3!c71588_g2_i2! A9C3P0! malectin(mlec)! MLEC!c98255_g1_i6! Q6P4P2! LMBR1!domain!containing!2b(lmbrd2b)! LMD2B!c96806_g1_i5! Q00341! high!density!lipoprotein!binding!protein(HDLBP)! VIGLN!c65925_g1_i1! Q5E9R3! EHEdomain!containing!1(EHD1)! EHD1!c84748_g1_i1! Q9QX82! CD164!molecule(Cd164)! MUC24!c94636_g2_i3! Q96FX8! PERP,!TP53!apoptosis!effector(PERP)! PERP!c89525_g2_i2! P35565! calnexin(Canx)! CALX!c98257_g2_i1! Q0P485! coiledEcoil!domain!containing!85C,!a(ccdc85ca)! C85CA!c90665_g2_i1! Q4KSH7! mitogen!activated!protein!kinase!kinase!7(Map2k7)! MP2K7!c98573_g1_i1! Q14542! solute!carrier!family!29!member!2(SLC29A2)! S29A2!
!
! 131!
c80853_g2_i1! P56524! histone!deacetylase!4(HDAC4)! HDAC4!c92441_g2_i6! Q86WA9! solute!carrier!family!26!member!11(SLC26A11)! S2611!c88202_g2_i1! Q13217! DnaJ!heat!shock!protein!family!(Hsp40)!member!C3(DNAJC3)! DNJC3!c89109_g3_i2! Q15599! SLC9A3!regulator!2(SLC9A3R2)! NHRF2!c74810_g1_i1! Q96JH7! valosin!containing!protein!interacting!protein!1(VCPIP1)! VCIP1!c98714_g2_i1! O95989! nudix!hydrolase!3(NUDT3)! NUDT3!c87939_g1_i2! P26990! ADP!ribosylation!factor!6(ARF6)! ARF6!c67696_g1_i1! Q7SXB5! PHD!finger!protein!23b(phf23b)! PF23B!c78733_g3_i1! Q28055! cAMP!regulated!phosphoprotein!19(ARPP19)! ARP19!c71948_g1_i1! Q5BJI9! signal!peptidase!complex!subunit!2(spcs2)! SPCS2!c87646_g3_i1! Q9BRS8! La!ribonucleoprotein!domain!family!member!6(LARP6)! LARP6!c93808_g1_i1! Q8BFW3! protein!phosphatase!1,!regulatory!(inhibitor)!subunit!15b(Ppp1r15b)! PR15B!c92817_g5_i1! Q86VZ5! sphingomyelin!synthase!1(SGMS1)! SMS1!c67943_g1_i1! Q9CQT9! RIKEN!cDNA!1110008F13!gene(1110008F13Rik)! CT024!c99574_g3_i7! Q13322! growth!factor!receptor!bound!protein!10(GRB10)! GRB10!c97422_g1_i3! P00170! cytochrome!b5!type!A!(microsomal)(CYB5A)! CYB5!c96131_g3_i1! Q13886! Kruppel!like!factor!9(KLF9)! KLF9!c84452_g1_i1! P15253! calreticulin(CALR)! CALR!c76195_g1_i2! Q9BRS8! La!ribonucleoprotein!domain!family!member!6(LARP6)! LARP6!c93734_g2_i4! Q62136! protein!tyrosine!phosphatase,!nonEreceptor!type!21(Ptpn21)! PTN21!c92678_g1_i1! Q9UG63! ATP!binding!cassette!subfamily!F!member!2(ABCF2)! ABCF2!
!
! 132!
c97862_g1_i1! Q08BL3!core!1!synthase,!glycoproteinENEacetylgalactosamine!3EbetaEgalactosyltransferase,!1a(c1galt1a)! C1GTA!
c93697_g1_i1! Q91VZ6! small!ArfGAP!1(Smap1)! SMAP1!c112500_g1_i1! P14210! hepatocyte!growth!factor(HGF)! HGF!c81099_g2_i1! Q9ESU6! bromodomain!containing!4(Brd4)! BRD4!c90374_g1_i3! P11507! ATPase!sarcoplasmic/endoplasmic!reticulum!Ca2+!transporting!2(Atp2a2)! AT2A2!c98192_g1_i7! O54804! choline!kinase!alpha(Chka)! CHKA!c68304_g1_i1! O00400! solute!carrier!family!33!member!1(SLC33A1)! ACATN!c85473_g1_i1! Q9NZQ7! CD274!molecule(CD274)! PD1L1!c87785_g1_i2! Q9NRH2! SNF!related!kinase(SNRK)! SNRK!c78734_g1_i3! Q9EPQ7! StARErelated!lipid!transfer!(START)!domain!containing!5(Stard5)! STAR5!c94426_g1_i1! P0CG55! ubiquitin!B(UBB)! UBB!c93710_g4_i2! Q5ZJN2! RAB11A,!member!RAS!oncogene!family(RAB11A)! RB11A!c94819_g3_i5! P11680! complement!factor!properdin(Cfp)! PROP!c47208_g1_i1! Q6DHL7! coiledEcoil!domain!containing!85C,!b(ccdc85cb)! C85CB!c88297_g1_i1! Q9Y2X8! ubiquitin!conjugating!enzyme!E2!D4!(putative)(UBE2D4)! UB2D4!c78660_g1_i2! Q9CQX5! claudin!domain!containing!1(Cldnd1)! CLDN1!c95641_g1_i4! Q8BMP6! acylECoenzyme!A!binding!domain!containing!3(Acbd3)! GCP60!c83055_g2_i2! Q5R8M1! serine/threonine!kinase!38(STK38)! STK38!c85389_g1_i3! Q80UF9! otopetrin!3(Otop3)! OTOP3!c91908_g2_i7! Q4TVV3! DEAD!(AspEGluEAlaEAsp)!box!polypeptide!46(ddx46)! DDX46!
!
! 133!
c99219_g2_i6! O42354! MDM2!oncogene,!E3!ubiquitin!protein!ligase(mdm2)! MDM2!c86946_g1_i1! P46094! XEC!motif!chemokine!receptor!1(XCR1)! XCR1!c92714_g1_i2! Q3B7Z2! oxysterol!binding!protein(Osbp)! OSBP1!c88394_g1_i1! Q5R8D0! UDPEgalactoseE4Eepimerase(GALE)! GALE!c87048_g1_i2! Q8K3K9! GTPase,!IMAP!family!member!4(Gimap4)! GIMA4!c93678_g1_i1! O42196! DnaJ!heat!shock!protein!family!(Hsp40)!member!C5!L!homeolog(dnajc5.L)! CSP!c89525_g1_i1! P27824! calnexin(CANX)! CALX!c98753_g2_i2! Q5ZLX5! zinc!finger!RANBP2Etype!containing!2(ZRANB2)! ZRAB2!c84011_g1_i1! P78381! solute!carrier!family!35!member!A2(SLC35A2)! S35A2!c99410_g1_i2! P36896! activin!A!receptor!type!1B(ACVR1B)! ACV1B!c98004_g2_i4! Q9EPE9! ATPase!type!13A1(Atp13a1)! AT131!c86637_g2_i1! Q9NVT9! armadillo!repeat!containing!1(ARMC1)! ARMC1!c94313_g2_i1! Q7SXF6! cysteineErich!with!EGFElike!domains!2(creld2)! CREL2!c85519_g2_i4! P15311! ezrin(EZR)! EZRI!c94567_g2_i2! Q9H2J7! solute!carrier!family!6!member!15(SLC6A15)! S6A15!c94334_g1_i1! Q2KI00! family!with!sequence!similarity!107!member!B(FAM107B)! F107B!c82944_g1_i1! Q5MPP0! fatty!acid!2Ehydroxylase(Fa2h)! FA2H!c89782_g2_i1! P21860! erbEb2!receptor!tyrosine!kinase!3(ERBB3)! ERBB3!c72921_g1_i1! Q8NCN2! zinc!finger!and!BTB!domain!containing!34(ZBTB34)! ZBT34!c92717_g2_i2! Q9W7C5! heparin!binding!EGF!like!growth!factor(HBEGF)! HBEGF!c75126_g1_i1! Q6ZQA6! immunoglobulin!superfamily,!member!3(Igsf3)! IGSF3!
!
! 134!
c95173_g1_i1! Q8CHP8! phosphoglycolate!phosphatase(Pgp)! PGP!c92174_g1_i4! Q9H0F5! ring!finger!protein!38(RNF38)! RNF38!c77246_g1_i1! Q70EL1! ubiquitin!specific!peptidase!54(USP54)! UBP54!
c95856_g2_i1! Q09325!mannosyl!(alphaE1,3E)Eglycoprotein!betaE1,2ENEacetylglucosaminyltransferase(Mgat1)! MGAT1!
c94342_g1_i3! Q7YQJ9! ubiquitin!conjugating!enzyme!E2!Q2(UBE2Q2)! UB2Q2!c89600_g2_i1! Q28F07! protein!arginine!methyltransferase!1(prmt1)! ANM1!c89754_g1_i1! Q62925! mitogenEactivated!protein!kinase!kinase!kinase!1(Map3k1)! M3K1!c80277_g2_i1! Q9Y4C8! RNA!binding!motif!protein!19(RBM19)! RBM19!c92607_g1_i2! Q99PF5! KHEtype!splicing!regulatory!protein(Khsrp)! FUBP2!c98573_g1_i2! Q14542! solute!carrier!family!29!member!2(SLC29A2)! S29A2!c99064_g1_i2! Q8N8Z6! discoidin,!CUB!and!LCCL!domain!containing!1(DCBLD1)! DCBD1!c78116_g1_i1! Q9D3X9! microfibrillarEassociated!protein!3Elike(Mfap3l)! MFA3L!c89525_g2_i1! P35565! calnexin(Canx)! CALX!c89409_g1_i3! Q4R5C7! signal!recognition!particle!14(SRP14)! SRP14!c92889_g1_i1! Q3THS6! methionine!adenosyltransferase!II,!alpha(Mat2a)! METK2!c87489_g1_i1! Q3UV16! inositol!1,4,5Etriphosphate!receptor!interacting!proteinElike!2(Itpripl2)! IPIL2!c96260_g1_i2! Q641F2! NEmyc!downstream!regulated!1!L!homeolog(ndrg1.L)! NDR1A!c91811_g2_i1! F1LMZ8! proteasome!26S!subunit,!nonEATPase!11(Psmd11)! PSD11!c96245_g3_i3! Q6IQ97! RNA!binding!motif!protein!4.1(rbm4.1)! RBM41!c87239_g3_i1! Q147X3! N(alpha)Eacetyltransferase!30,!NatC!catalytic!subunit(NAA30)! NAA30!
!
! 135!
c79909_g1_i6! Q9HBU6! ethanolamine!kinase!1(ETNK1)! EKI1!c96689_g2_i2! Q687X5! STEAP4!metalloreductase(STEAP4)! STEA4!c97300_g3_i3! Q99LQ7! transmembrane!protein!189(Tmem189)! TM189!c99289_g2_i1! Q9UBJ2! ATP!binding!cassette!subfamily!D!member!2(ABCD2)! ABCD2!c79909_g1_i4! Q9HBU6! ethanolamine!kinase!1(ETNK1)! EKI1!c67181_g1_i1! Q71SY6! out!at!first!homolog(OAF)! OAF!c91477_g2_i1! Q3T0E1! exosome!component!3(EXOSC3)! EXOS3!c90046_g1_i1! P80303! nucleobindin!2(NUCB2)! NUCB2!c92208_g1_i3! P21860! erbEb2!receptor!tyrosine!kinase!3(ERBB3)! ERBB3!c85103_g1_i2! Q7ZVZ7! abhydrolase!domain!containing!17C(abhd17c)! F108C!
c95856_g3_i1! P27115!mannosyl!(alphaE1,3E)Eglycoprotein!betaE1,2ENEacetylglucosaminyltransferase(MGAT1)! MGAT1!
c38365_g1_i1! Q9ULL1! pleckstrin!homology!and!RhoGEF!domain!containing!G1(PLEKHG1)! PKHG1!c86481_g1_i2! O46674! ATPase!sarcoplasmic/endoplasmic!reticulum!Ca2+!transporting!2(ATP2A2)! AT2A2!c99092_g1_i7! Q7M6Y3! phosphatidylinositol!binding!clathrin!assembly!protein(Picalm)! PICA!c86065_g1_i1! Q8TEK3! DOT1!like!histone!lysine!methyltransferase(DOT1L)! DOT1L!c99993_g1_i2! O43149! zinc!finger!ZZEtype!and!EFEhand!domain!containing!1(ZZEF1)! ZZEF1!c90769_g2_i8! Q8TE68! EPS8!like!1(EPS8L1)! ES8L1!c98061_g1_i4! Q8BJR6! protease,!serine!27(Prss27)! PRS27!c97316_g1_i1! Q9DA37! sterile!alpha!motif!domain!containing!8(Samd8)! SAMD8!c85740_g3_i3! Q99PP9! tripartite!motifEcontaining!16(Trim16)! TRI16!
!
! 136!
c86989_g1_i1! Q7TSZ8!nucleus!accumbens!associated!1,!BEN!and!BTB!(POZ)!domain!containing(Nacc1)! NACC1!
c97362_g1_i1! Q99K28! ADPEribosylation!factor!GTPase!activating!protein!2(Arfgap2)! ARFG2!c95315_g1_i2! Q08DN6! CDC42!effector!protein!2(CDC42EP2)! BORG1!c85575_g1_i1! Q8VE97! serine/arginineErich!splicing!factor!4(Srsf4)! SRSF4!c99253_g1_i1! P97784! cryptochrome!1!(photolyaseElike)(Cry1)! CRY1!c95379_g1_i1! Q8C0J6! sosondowah!ankyrin!repeat!domain!family!member!C(Sowahc)! SWAHC!c90769_g2_i6! Q8TE68! EPS8!like!1(EPS8L1)! ES8L1!c9980_g1_i1! Q9Z2G0! feminization!1!homolog!b!(C.!elegans)(Fem1b)! FEM1B!c93621_g1_i1! A8E7C5! inositol!polyphosphateE5Ephosphatase!F(inpp5f)! SAC2!c87971_g1_i2! Q90687! protein!tyrosine!phosphatase,!nonEreceptor!type!11(PTPN11)! PTN11!c95836_g1_i4! Q9NUE0! zinc!finger!DHHCEtype!containing!18(ZDHHC18)! ZDH18!c92330_g1_i1! Q9UM82! spermatogenesis!associated!2(SPATA2)! SPAT2!
c92874_g1_i3! Q9JMK0!UDPEGal:betaGlcNAc!beta!1,4Egalactosyltransferase,!polypeptide!5(B4galt5)! B4GT5!
c93659_g2_i3! O60885! bromodomain!containing!4(BRD4)! BRD4!c90374_g1_i2! Q03669! ATPase,!Ca++!transporting,!cardiac!muscle,!slow!twitch!2(ATP2A2)! AT2A2!c91507_g1_i1! Q925R7! polypeptide!NEacetylgalactosaminyltransferase!10(Galnt10)! GLT10!c87909_g2_i3! O35343! karyopherin!(importin)!alpha!4(Kpna4)! IMA4!c82939_g1_i5! Q10471! polypeptide!NEacetylgalactosaminyltransferase!2(GALNT2)! GALT2!c99464_g3_i1! P84079! ADPEribosylation!factor!1(Arf1)! ARF1!
!
! 137!
c97567_g1_i2! Q08DQ2! glutamineEfructoseE6Ephosphate!transaminase!2(GFPT2)! GFPT2!c83330_g1_i1! Q6PC19! SSU72!homolog,!RNA!polymerase!II!CTD!phosphatase(ssu72)! SSU72!c85380_g3_i1! Q6TLE4! membrane!magnesium!transporter!1(mmgt1)! MMGT1!c84389_g2_i1! Q90ZM2! Sec61!translocon!alpha!1!subunit(sec61a1)! S61A1!c69632_g1_i1! Q17R14! myosin!ID(MYO1D)! MYO1D!c95980_g1_i5! Q8R2E9! ERO1Elike!beta!(S.!cerevisiae)(Ero1lb)! ERO1B!c89475_g1_i1! P07237! prolyl!4Ehydroxylase!subunit!beta(P4HB)! PDIA1!c95641_g1_i1! Q7TNY6! acylECoA!binding!domain!containing!3(Acbd3)! GCP60!c99112_g1_i1! Q8TDX6! chondroitin!sulfate!NEacetylgalactosaminyltransferase!1(CSGALNACT1)! CGAT1!c89053_g1_i1! O14681! EI24,!autophagy!associated!transmembrane!protein(EI24)! EI24!c96429_g1_i1! P22907! hydroxymethylbilane!synthase(Hmbs)! HEM3!c83644_g1_i2! A9JRC7! protein!phosphatase!4,!catalytic!subunit!b(ppp4cb)! PP4CB!c76660_g1_i1! O95819! mitogenEactivated!protein!kinase!kinase!kinase!kinase!4(MAP4K4)! M4K4!c85472_g1_i1! A8WGS4! TLC!domain!containing!2(tlcd2)! TLCD2!c89930_g1_i1! Q86V48! leucine!zipper!protein!1(LUZP1)! LUZP1!c99751_g1_i2! Q5TZ80! hook!microtubuleEtethering!protein!1(hook1)! HOOK1!c87789_g1_i1! Q96SZ5! 2Eaminoethanethiol!dioxygenase(ADO)! AEDO!c83644_g1_i6! A9JRC7! protein!phosphatase!4,!catalytic!subunit!b(ppp4cb)! PP4CB!c72883_g1_i1! P52804! ephrinEA5(EFNA5)! EFNA5!c94019_g3_i1! O08586! phosphatase!and!tensin!homolog(Pten)! PTEN!c97469_g1_i1! O60266! adenylate!cyclase!3(ADCY3)! ADCY3!
!
! 138!
c93432_g1_i4! P06909! complement!component!factor!h(Cfh)! CFAH!c87482_g1_i2! Q6P8Y1! calcyphosineElike(Capsl)! CAPSL!c99195_g3_i1! Q6GMF8! rhomboid!5!homolog!1a!(Drosophila)(rhbdf1a)! RHDF1!c82838_g4_i4! Q8TF01! PNN!interacting!serine!and!arginine!rich!protein(PNISR)! PNISR!c99549_g1_i3! A6QNT8! SEC24!homolog!A,!COPII!coat!complex!component(SEC24A)! SC24A!c90244_g2_i1! Q504E7! SUZ!RNA!binding!domain!containing!1(szrd1)! SZRD1!c99917_g2_i1! Q14435! polypeptide!NEacetylgalactosaminyltransferase!3(GALNT3)! GALT3!c97873_g1_i4! O93449! transforming!growth!factor,!beta!1(tgf)! TGFB1!c99410_g1_i1! P36896! activin!A!receptor!type!1B(ACVR1B)! ACV1B!c95905_g3_i1! A0AAS4! sphingomyelin!synthase!1(SGMS1)! SMS1!c92876_g2_i2! O95819! mitogenEactivated!protein!kinase!kinase!kinase!kinase!4(MAP4K4)! M4K4!c95703_g2_i1! Q09666! AHNAK!nucleoprotein(AHNAK)! AHNK!c90111_g1_i1! O14896! interferon!regulatory!factor!6(IRF6)! IRF6!c89444_g3_i8! Q4KM14! tRNA!selenocysteine!1!associated!protein!1b(trnau1apb)! TSP1L!c72963_g1_i1! O60443! DFNA5,!deafness!associated!tumor!suppressor(DFNA5)! DFNA5!c83312_g3_i2! Q28BP2! transmembrane!protein!150A(tmem150a)! T150A!c95725_g4_i3! Q13017! Rho!GTPase!activating!protein!5(ARHGAP5)! RHG05!c73931_g2_i1! Q7T2A3! DET1!and!DDB1!associated!1(dda1)! DDA1!c84961_g1_i1! Q96SZ5! 2Eaminoethanethiol!dioxygenase(ADO)! AEDO!c75695_g3_i1! P36380! gap!junction!protein,!beta!4(Gjb4)! CXB4!c93176_g1_i4! Q5E9R3! EHEdomain!containing!1(EHD1)! EHD1!
!
! 139!
c75614_g2_i1! Q6NVU2! protein!phosphatase!1,!catalytic!subunit,!gamma!isozyme(ppp1cc)! PPIG!c92857_g1_i1! Q9DCL8! protein!phosphatase!1,!regulatory!(inhibitor)!subunit!2(Ppp1r2)! IPP2!c91475_g2_i1! Q66J96! nudE!neurodevelopment!protein!1!L!homeolog(nde1.L)! NDE1A!c76615_g1_i1! P35414! apelin!receptor(APLNR)! APJ!c97019_g1_i1! Q9H4Z2! zinc!finger!protein!335(ZNF335)! ZN335!c65548_g2_i1! Q6NWG4! protein!arginine!methyltransferase!6(prmt6)! ANM6!c93674_g2_i1! A5D7D1! actinin!alpha!4(ACTN4)! ACTN4!c90454_g1_i1! P47758! signal!recognition!particle!receptor,!B!subunit(Srprb)! SRPRB!c76759_g1_i3! Q3MII6! TBC1!domain!family!member!25(TBC1D25)! TBC25!c92456_g1_i2! Q9Y251! heparanase(HPSE)! HPSE!c81064_g1_i1! Q9Y3A6! transmembrane!p24!trafficking!protein!5(TMED5)! TMED5!c97706_g1_i5! Q5ZKL6! membrane!bound!OEacyltransferase!domain!containing!2(MBOAT2)! MBOA2!c91285_g1_i8! Q6PGG2! GemEinteracting!protein(Gmip)! GMIP!c71317_g1_i1! Q7SZE5! Sec23!homolog!A,!COPII!coat!complex!component(sec23a)! SC23A!c95703_g2_i2! Q09666! AHNAK!nucleoprotein(AHNAK)! AHNK!c81656_g1_i1! Q7SY06! 3EhydroxyacylECoA!dehydratase!3(hacd3)! HADC!c77097_g1_i1! Q68EK7! RAB4B,!member!RAS!oncogene!family(rab4b)! RAB4B!c99549_g1_i2! O95486! SEC24!homolog!A,!COPII!coat!complex!component(SEC24A)! SC24A!c94726_g1_i2! Q71RC2! La!ribonucleoprotein!domain!family!member!4(LARP4)! LARP4!c74164_g1_i1! Q7ZWE9! cytidylate!kinase(cmpk)! KCY!c93426_g1_i2! Q6PA06! atlastin!GTPase!2(Atl2)! ATLA2!
!
! 140!
c90961_g1_i1! Q8QFP8! LIM!domain!kinase!1(LIMK1)! LIMK1!c98004_g2_i1! Q9EPE9! ATPase!type!13A1(Atp13a1)! AT131!c98576_g2_i1! Q92802! NEDD4!binding!protein!2!like!2(N4BP2L2)! N42L2!c112330_g1_i1! Q6N075! major!facilitator!superfamily!domain!containing!5(MFSD5)! MFSD5!c94384_g1_i1! P13667! protein!disulfide!isomerase!family!A!member!4(PDIA4)! PDIA4!c86824_g1_i1! Q8TCT9! histocompatibility!minor!13(HM13)! HM13!c80181_g1_i2! Q9H4Z2! zinc!finger!protein!335(ZNF335)! ZN335!c92714_g1_i1! Q5QNQ6! oxysterol!binding!protein!2(Osbp2)! OSBP2!c56938_g1_i1! O14772! fucoseE1Ephosphate!guanylyltransferase(FPGT)! FPGT!c95959_g1_i2! Q8R366! immunoglobulin!superfamily,!member!8(Igsf8)! IGSF8!c87906_g2_i1! Q96T37! RNA!binding!motif!protein!15(RBM15)! RBM15!c87636_g3_i1! P49138! MAP!kinaseEactivated!protein!kinase!2(Mapkapk2)! MAPK2!c82188_g1_i2! Q5XJA3! prolineErich!coiledEcoil!1(prrc1)! PRRC1!c96233_g1_i2! O35709! ectodermalEneural!cortex!1(Enc1)! ENC1!c76214_g1_i1! Q86X83! COMM!domain!containing!2(COMMD2)! COMD2!c91801_g1_i4! Q7ZXY0! inositolE3Ephosphate!synthase!1!S!homeolog(isyna1.S)! INO1A!
c96211_g1_i2! Q91ZW3!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!a,!member!5(Smarca5)! SMCA5!
c91869_g3_i1! Q9NUQ3! taxilin!gamma(TXLNG)! TXLNG!c78117_g1_i1! Q9H6F5! coiledEcoil!domain!containing!86(CCDC86)! CCD86!c99464_g2_i2! P51643! ADP!ribosylation!factor!5!L!homeolog(arf5.L)! ARF1!
!
! 141!
c86097_g1_i1! P00167! cytochrome!b5!type!A(CYB5A)! CYB5!c90812_g1_i3! P61087! ubiquitinEconjugating!enzyme!E2K(Ube2k)! UBE2K!c86435_g2_i1! Q9DBG7! signal!recognition!particle!receptor!('docking!protein')(Srpr)! SRPR!c89912_g5_i2! Q60803! TNF!receptorEassociated!factor!3(Traf3)! TRAF3!c85956_g1_i5! Q7SXX7! multivesicular!body!subunit!12A(mvb12a)! MB12A!c84452_g1_i2! P15253! calreticulin(CALR)! CALR!c95317_g1_i1! P67963! casein!kinase!1,!alpha!1!L!homeolog(csnk1a1.L)! KC1A!c88071_g4_i1! Q03669! ATPase,!Ca++!transporting,!cardiac!muscle,!slow!twitch!2(ATP2A2)! AT2A2!c97453_g3_i3! P46061! RAN!GTPase!activating!protein!1(Rangap1)! RAGP1!c87048_g1_i1! Q8K3K9! GTPase,!IMAP!family!member!4(Gimap4)! GIMA4!c91673_g2_i1! Q9TR36! phosphatidylinositol!transfer!protein!beta(PITPNB)! PIPNB!c86824_g1_i2! Q8TCT9! histocompatibility!minor!13(HM13)! HM13!c74062_g2_i1! Q6PBA2! LSM12!homolog!b(lsm12b)! LS12A!c99978_g1_i2! Q07617! sperm!associated!antigen!1(SPAG1)! SPAG1!c65299_g3_i1! Q9QXS1! plectin(Plec)! PLEC!c79711_g3_i1! Q8K021! secretory!carrier!membrane!protein!1(Scamp1)! SCAM1!c86543_g1_i1! Q58D45! cell!death!inducing!p53!target!1(CDIP1)! CDIP1!c83253_g1_i4! P56545! CEterminal!binding!protein!2(CTBP2)! CTBP2!c87567_g1_i1! Q90ZN1! BCL2!like!10(BCL2L10)! NR13!c92055_g2_i4! P15428! hydroxyprostaglandin!dehydrogenase!15E(NAD)(HPGD)! PGDH!c99754_g1_i1! Q14596! NBR1,!autophagy!cargo!receptor(NBR1)! NBR1!
!
! 142!
c87697_g3_i5! O14562! ubiquitin!family!domain!containing!1(UBFD1)! UBFD1!c97864_g4_i1! Q13772! nuclear!receptor!coactivator!4(NCOA4)! NCOA4!c94228_g1_i2! Q6P3W7! SCY1!like!pseudokinase!2(SCYL2)! SCYL2!c90795_g2_i5! P17844! DEADEbox!helicase!5(DDX5)! DDX5!c71565_g1_i1! Q6P9Z4! femE1!homolog!a!(C.!elegans)(fem1a)! FEM1A!c96924_g1_i2! Q7Z7L9! zinc!finger!and!SCAN!domain!containing!2(ZSCAN2)! ZSCA2!c86451_g1_i2! P62498! eukaryotic!translation!termination!factor!1(etf1)! ERF1!c94988_g1_i2! Q8N8Q1! cytochrome!b561!family!member!D1(CYB561D1)! C56D1!c84452_g1_i3! P15253! calreticulin(CALR)! CALR!c84370_g1_i3! Q6P964! protein!phosphatase!4,!regulatory!subunit!2a(ppp4r2a)! P4R2A!c96703_g1_i2! Q66HD0! heat!shock!protein!90!beta!family!member!1(Hsp90b1)! ENPL!c94137_g1_i2! Q28296! mal,!TEcell!differentiation!protein(MAL)! MAL!c94896_g1_i1! Q1LVV0! family!with!sequence!similarity!83,!member!Hb(fam83hb)! FA83H!c84535_g1_i8! P55010! eukaryotic!translation!initiation!factor!5(EIF5)! IF5!c97157_g2_i6! Q5ZIZ4! 5'Enucleotidase,!cytosolic!II(NT5C2)! 5NTC!c90681_g1_i1! Q9H553! ALG2,!alphaE1,3/1,6Emannosyltransferase(ALG2)! ALG2!c93150_g1_i1! Q8NHV1! GTPase,!IMAP!family!member!7(GIMAP7)! GIMA7!c97484_g1_i3! Q9NR21! poly(ADPEribose)!polymerase!family!member!11(PARP11)! PAR11!c92876_g2_i1! O95819! mitogenEactivated!protein!kinase!kinase!kinase!kinase!4(MAP4K4)! M4K4!
c83033_g3_i2! Q5PRD0!tyrosine!3Emonooxygenase/tryptophan!5Emonooxygenase!activation!protein,!beta!polypeptide!a(ywhaba)! 143BA!
!
! 143!
c90244_g3_i2! Q504E7! SUZ!RNA!binding!domain!containing!1(szrd1)! SZRD1!c90795_g2_i3! P17844! DEADEbox!helicase!5(DDX5)! DDX5!c97433_g1_i4! Q8K3K9! GTPase,!IMAP!family!member!4(Gimap4)! GIMA4!c90374_g1_i1! P11507! ATPase!sarcoplasmic/endoplasmic!reticulum!Ca2+!transporting!2(Atp2a2)! AT2A2!c88957_g1_i3! Q5FVR1! zinc!finger,!DHHCEtype!containing!4(Zdhhc4)! ZDHC4!c81057_g2_i1! Q9Z255! ubiquitinEconjugating!enzyme!E2A(Ube2a)! UBE2A!c77595_g1_i1! Q9H9H4! VPS37B,!ESCRTEI!subunit(VPS37B)! VP37B!c99937_g3_i3! Q80V42! carboxypeptidase!M(Cpm)! CBPM!c96350_g1_i1! Q8NFA2! NADPH!oxidase!organizer!1(NOXO1)! NOXO1!c95870_g2_i3! P42679! megakaryocyteEassociated!tyrosine!kinase(MATK)! MATK!c72744_g1_i1! Q6P0I8! exosome!component!6(exosc6)! EXOS6!c97416_g1_i3! Q9Y548! Yip1!domain!family!member!1(YIPF1)! YIPF1!c93873_g2_i2! Q9UKF7! phosphatidylinositol!transfer!protein,!cytoplasmic!1(PITPNC1)! PITC1!c96305_g1_i1! P97554! DnaJ!heat!shock!protein!family!(Hsp40)!member!B9(Dnajb9)! DNJB9!c81635_g1_i3! Q8R332! nucleoporin!like!1(Nupl1)! NUPL1!c89796_g1_i1! Q9DBA6! trypsin!domain!containing!1(Tysnd1)! TYSD1!c88172_g1_i1! Q6DHN3! TM2!domain!containing!2(tm2d2)! TM2D2!c88762_g2_i2! Q7ZUB3! tetraspanin!31(tspan31)! TSN31!c86358_g2_i1! P11179! dihydrolipoamide!SEsuccinyltransferase(DLST)! ODO2!c96459_g2_i1! Q5XI68! downEregulator!of!transcription!1,!TBPEbinding!(negative!cofactor!2)(Dr1)! NC2B!
!
! 144!
c91376_g4_i1! Q7Z429!glutamate!ionotropic!receptor!NMDA!type!subunit!associated!protein!1(GRINA)! LFG1!
c92723_g1_i3! Q8BGS7! choline/ethanolaminephosphotransferase!1(Cept1)! CEPT1!c98586_g1_i4! A1L1G1! epithelial!splicing!regulatory!protein!1(esrp1)! ESRP1!c88663_g1_i1! Q02790! FK506!binding!protein!4(FKBP4)! FKBP4!c98474_g1_i1! P45429! small!nuclear!ribonucleoprotein!polypeptide!A!S!homeolog(snrpa.S)! SNRPA!c89693_g1_i2! P46109! CRK!like!protoEoncogene,!adaptor!protein(CRKL)! CRKL!c75882_g2_i1! Q7ZV20! ribosomal!RNA!processing!15!homolog(rrp15)! RRP15!c94656_g1_i1! Q66HX0! solute!carrier!family!35,!member!B1(slc35b1)! S35B1!c76476_g1_i1! Q5MNU5! SREBF!chaperone(SCAP)! SCAP!c90957_g1_i4! P63150! protein!phosphatase!2!regulatory!subunit!Balpha(PPP2R2A)! 2ABA!c81694_g1_i2! Q5PPI1! serine!and!arginine!rich!splicing!factor!9(Srsf9)! SRSF9!c98154_g3_i1! Q5SWA1! protein!phosphatase!1!regulatory!subunit!15B(PPP1R15B)! PR15B!c95230_g1_i14! Q9Y616! interleukin!1!receptor!associated!kinase!3(IRAK3)! IRAK3!c91281_g5_i4! Q9ESU6! bromodomain!containing!4(Brd4)! BRD4!c98950_g1_i2! Q6DK99! cornifelin!homolog!B(cnfnEb)! CNFNB!c83950_g1_i4! O70377! synaptosomalEassociated!protein!23(Snap23)! SNP23!c92783_g4_i1! Q5XIY2! transmembrane!protein!56b(tmem56b)! TM56B!c88909_g4_i1! Q28E01! solute!carrier!family!20!(phosphate!transporter),!member!2(slc20a2)! S20A2!c88738_g2_i1! Q8N5I2! arrestin!domain!containing!1(ARRDC1)! ARRD1!c77894_g1_i1! P37397! calponin!3(Cnn3)! CNN3!
!
! 145!
c85993_g1_i1! Q9Y3E0! golgi!transport!1B(GOLT1B)! GOT1B!c97899_g1_i1! Q1LY46! leucine!zipperEEFEhand!containing!transmembrane!protein!1(letm1)! LETM1!c90859_g3_i1! Q5EA75! phosphate!cytidylyltransferase!2,!ethanolamine(PCYT2)! PCY2!c90500_g2_i5! Q8TE68! EPS8!like!1(EPS8L1)! ES8L1!c98471_g1_i1! Q9UBM8! MGAT4!family!member!C(MGAT4C)! MGT4C!c94781_g1_i3! A1L3F5! cEMaf!inducing!protein!L!homeolog(cmip.L)! CMIP!c98004_g2_i2! Q9EPE9! ATPase!type!13A1(Atp13a1)! AT131!c87438_g1_i1! O43399! tumor!protein!D52!like!2(TPD52L2)! TPD54!c98950_g1_i3! Q6DK99! cornifelin!homolog!B(cnfnEb)! CNFNB!c78710_g1_i1! Q9D1Q6! endoplasmic!reticulum!protein!44(Erp44)! ERP44!c89199_g2_i1! P19367! hexokinase!1(HK1)! HXK1!c95454_g1_i2! Q9Y673! ALG5,!dolichylEphosphate!betaEglucosyltransferase(ALG5)! ALG5!c87695_g4_i2! Q8NEG4! family!with!sequence!similarity!83!member!F(FAM83F)! FA83F!c82362_g1_i1! Q7TSV3! zinc!finger,!MYNDEtype!containing!19(Zmynd19)! ZMY19!c73818_g1_i3! A6QLR3! family!with!sequence!similarity!175!member!B(FAM175B)! F175B!c97436_g1_i5! Q9BYJ9! YTH!N6Emethyladenosine!RNA!binding!protein!1(YTHDF1)! YTHD1!c73945_g1_i1! Q9UQ80! proliferationEassociated!2G4(PA2G4)! PA2G4!c83033_g3_i3! Q6UFZ9! 14E3E3B1!protein(LOC100136192)! 143B1!c83162_g1_i4! Q86TL2! transmembrane!protein!110(TMEM110)! TM110!c79066_g1_i1! P51644! ADP!ribosylation!factor!4(arf4)! ARF4!c97752_g2_i1! P31943! heterogeneous!nuclear!ribonucleoprotein!H1!(H)(HNRNPH1)! HNRH1!
!
! 146!
c68257_g1_i1! Q6DH26! mediator!complex!subunit!31(med31)! MED31!c58157_g1_i1! Q8BFQ9! kelchElike!42(Klhl42)! KLH42!c93005_g3_i2! Q7SZE5! Sec23!homolog!A,!COPII!coat!complex!component(sec23a)! SC23A!c84837_g1_i2! O95628! CCR4ENOT!transcription!complex!subunit!4(CNOT4)! CNOT4!c97742_g2_i1! P32507! nectin!cell!adhesion!molecule!2(Nectin2)! PVRL2!c91027_g1_i1! P30679! G!protein!subunit!alpha!15(GNA15)! GNA15!c90111_g1_i2! O14896! interferon!regulatory!factor!6(IRF6)! IRF6!c72022_g1_i3! Q6PEV3! WAS/WASL!interacting!protein!family,!member!2(Wipf2)! WIPF2!c84214_g1_i1! Q5HZT9! DnaJ!heat!shock!protein!family!(Hsp40)!member!C25(dnajc25)! DJC25!c82944_g2_i1! Q4R4P4! fatty!acid!2Ehydroxylase(FA2H)! FA2H!c92536_g2_i1! Q8JHE9! APH1B!gamma!secretase!subunit(aph1b)! APH1B!c99094_g1_i1! O62675! interleukin!16(IL16)! IL16!c66454_g1_i2! Q8N4B1! family!with!sequence!similarity!109!member!A(FAM109A)! SESQ1!c96299_g3_i2! Q99PP9! tripartite!motifEcontaining!16(Trim16)! TRI16!c84316_g1_i3! Q01433! adenosine!monophosphate!deaminase!2(AMPD2)! AMPD2!c99757_g1_i3! Q8CHN6! sphingosineE1Ephosphate!lyase!1(Sgpl1)! SGPL1!c99135_g3_i6! A4IG61! mitochondrial!elongation!factor!1(mief1)! MID51!c92484_g1_i3! B5X3B2! adipocyte!plasma!membrane!associated!protein(apmap)! APMAP!c85934_g1_i2! P37980! pyrophosphatase!(inorganic)!1(PPA1)! IPYR!c98969_g2_i2! Q08CX2! SH2!domain!containing!4A(sh2d4a)! SH24A!c93903_g2_i2! Q1W674! hexokinase!2(HK2)! HXK2!
!
! 147!
c85718_g2_i6! Q9ULY5! CEtype!lectin!domain!family!4!member!E(CLEC4E)! CLC4E!c83312_g3_i7! Q28BP2! transmembrane!protein!150A(tmem150a)! T150A!c95965_g1_i1! Q6PGY5! DnaJ!(Hsp40)!homolog,!subfamily!C,!member!21(dnajc21)! DJC21!c94019_g2_i2! Q1LY46! leucine!zipperEEFEhand!containing!transmembrane!protein!1(letm1)! LETM1!c94470_g1_i2! Q96MW5! component!of!oligomeric!golgi!complex!8(COG8)! COG8!c87402_g2_i1! Q6P4U6! zinc!and!ring!finger!1(znrf1)! ZNRF1!c89620_g1_i3! P70372! ELAV!(embryonic!lethal,!abnormal!vision)Elike!1!(Hu!antigen!R)(Elavl1)! ELAV1!c24989_g1_i1! Q63357! myosin!ID(Myo1d)! MYO1D!c99465_g1_i3! A1A5V7! transmembrane!protein!41B(tmem41b)! TM41B!c98596_g1_i2! Q86VR2! family!with!sequence!similarity!134!member!C(FAM134C)! F134C!c69683_g2_i2! Q5ZJN4! ubiquitin!specific!peptidase!10(USP10)! UBP10!
c96760_g1_i4! P25799!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!B!cells!1,!p105(Nfkb1)! NFKB1!
c86510_g2_i1! O70293! G!proteinEcoupled!receptor!kinase!6(Grk6)! GRK6!c87875_g2_i2! Q91YE3! eglE9!family!hypoxiaEinducible!factor!1(Egln1)! EGLN1!c85892_g1_i1! Q9Y2H1! serine/threonine!kinase!38!like(STK38L)! ST38L!c93922_g3_i1! Q76N33! STAM!binding!protein!like!1(Stambpl1)! STALP!c98963_g1_i3! Q61190! interleukin!10!receptor,!beta(Il10rb)! I10R2!c92907_g1_i3! O75808! calpain!15(CAPN15)! CAN15!c93195_g1_i1! P50636! ring!finger!protein!19A(Rnf19a)! RN19A!c85945_g1_i1! Q6P825! translocase!of!outer!mitochondrial!membrane!40!homolog(tomm40)! TOM40!
!
! 148!
c91908_g2_i1! Q4TVV3! DEAD!(AspEGluEAlaEAsp)!box!polypeptide!46(ddx46)! DDX46!c89931_g2_i1! Q6NWZ9! cysteine!dioxygenase,!type!I(cdo1)! CDO1!c92040_g1_i1! Q96T37! RNA!binding!motif!protein!15(RBM15)! RBM15!c81929_g1_i1! O15127! secretory!carrier!membrane!protein!2(SCAMP2)! SCAM2!c85569_g5_i1! P34997! CEXEC!motif!chemokine!receptor!5(Cxcr5)! CXCR5!c93659_g3_i1! O60885! bromodomain!containing!4(BRD4)! BRD4!c88526_g1_i4! Q8IU60! decapping!mRNA!2(DCP2)! DCP2!c96658_g1_i2! Q5RD27! SRSF!protein!kinase!1(SRPK1)! SRPK1!c48622_g1_i1! Q9NZ20! phospholipase!A2!group!III(PLA2G3)! PA2G3!c93750_g1_i2! Q5RAL9! glucosamineEphosphate!NEacetyltransferase!1(GNPNAT1)! GNA1!c99505_g1_i2! Q14978! nucleolar!and!coiledEbody!phosphoprotein!1(NOLC1)! NOLC1!c89121_g1_i2! Q12891! hyaluronoglucosaminidase!2(HYAL2)! HYAL2!c89417_g1_i3! Q8TBZ5! zinc!finger!protein!502(ZNF502)! ZN502!c92857_g1_i2! Q9DCL8! protein!phosphatase!1,!regulatory!(inhibitor)!subunit!2(Ppp1r2)! IPP2!
c84970_g3_i1! Q8CGK7!guanine!nucleotide!binding!protein,!alpha!stimulating,!olfactory!type(Gnal)! GNAL!
c85755_g1_i1! Q90Y50! coxsackie!virus!and!adenovirus!receptor(cxadr)! CXAR!c99937_g3_i1! Q80V42! carboxypeptidase!M(Cpm)! CBPM!c83018_g1_i2! O75460! endoplasmic!reticulum!to!nucleus!signaling!1(ERN1)! ERN1!c90648_g1_i2! Q9H3F6! potassium!channel!tetramerization!domain!containing!10(KCTD10)! BACD3!c55952_g1_i1! Q96AE4! far!upstream!element!binding!protein!1(FUBP1)! FUBP1!
!
! 149!
c83299_g1_i1! Q8R366! immunoglobulin!superfamily,!member!8(Igsf8)! IGSF8!c91466_g2_i1! P00125! cytochrome!cE1(CYC1)! CY1!c93515_g2_i6! P41971! ELK3,!member!of!ETS!oncogene!family(Elk3)! ELK3!c96033_g4_i1! Q5U316! RAB35,!member!RAS!oncogene!family(Rab35)! RAB35!c93440_g2_i1! Q6PD83! basic!leucine!zipper!and!W2!domains!1a(bzw1a)! BZW1A!c70797_g1_i1! Q969P0! immunoglobulin!superfamily!member!8(IGSF8)! IGSF8!c94906_g1_i3! Q9Y2U8! LEM!domain!containing!3(LEMD3)! MAN1!c79711_g2_i1! O77735! secretory!carrier!membrane!protein!1(SCAMP1)! SCAM1!c72851_g1_i1! A9JRC7! protein!phosphatase!4,!catalytic!subunit!b(ppp4cb)! PP4CB!c86293_g2_i4! Q13077! TNF!receptor!associated!factor!1(TRAF1)! TRAF1!c99442_g1_i1! Q2VB19! pumilio!RNAEbinding!family!member!1(PUM1)! PUM1!c94064_g1_i1! A1A4N1! solute!carrier!family!29!(nucleoside!transporters),!member!3(SLC29A3)! S29A3!c95341_g2_i1! Q6A028! SWAE70!protein(Swap70)! SWP70!c13252_g1_i1! Q91YD1! gap!junction!protein,!delta!3(Gjd3)! CXD3!c97264_g1_i16! Q96T60! polynucleotide!kinase!3'Ephosphatase(PNKP)! PNKP!c79304_g1_i1! P51643! ADP!ribosylation!factor!5!L!homeolog(arf5.L)! ARF1!c84681_g2_i1! Q6DC93! pentaEEFEhand!domain!containing!1(pef1)! PEF1!c97058_g1_i1! Q5F3I6! transmembrane!protein!104(TMEM104)! TM104!c79070_g2_i2! Q99729! heterogeneous!nuclear!ribonucleoprotein!A/B(HNRNPAB)! ROAA!c82747_g1_i1! Q6NWJ4! DnaJ!(Hsp40)!homolog,!subfamily!C,!member!2(dnajc2)! DNJC2!c82512_g1_i2! Q3MHV6! SLAIN!motif!family!member!2(SLAIN2)! SLAI2!
!
! 150!
c86738_g1_i1! P15622! zinc!finger!protein!250(ZNF250)! ZN250!c95951_g1_i2! Q99PF5! KHEtype!splicing!regulatory!protein(Khsrp)! FUBP2!c87857_g1_i1! Q8K3Z9! nuclear!pore!membrane!protein!121(Pom121)! PO121!c94546_g1_i4! Q8C341! SUN!domain!containing!ossification!factor(Suco)! SUCO!c94641_g2_i1! Q5FWR8! poliovirus!receptorErelated!4(pvrl4)! PVRL4!c88399_g1_i2! D3YYI7! ring!finger!protein!217(Rnf217)! RN217!c99505_g2_i1! P41777! nucleolar!and!coiledEbody!phosphoprotein!1(Nolc1)! NOLC1!c78743_g1_i1! Q6P9X4! protein!tyrosine!phosphatase!type!IVA,!member!2(Ptp4a2)! TP4A2!c82346_g2_i2! Q00653! nuclear!factor!kappa!B!subunit!2(NFKB2)! NFKB2!c13596_g1_i1! Q1L8I0! pseudouridylate!synthase!7Elike(pus7l)! PUS7L!c93221_g1_i3! Q96G75! required!for!meiotic!nuclear!division!5!homolog!B(RMND5B)! RMD5B!c88549_g2_i2! Q6GMF8! rhomboid!5!homolog!1a!(Drosophila)(rhbdf1a)! RHDF1!c98443_g4_i2! P29119! furin!(paired!basic!amino!acid!cleaving!enzyme)!S!homeolog(furin.S)! FURI1!c92609_g1_i4! Q8AXU9! SH3Edomain!GRB2Elike!3(SH3GL3)! SH3G3!c83644_g1_i8! A9JRC7! protein!phosphatase!4,!catalytic!subunit!b(ppp4cb)! PP4CB!c92795_g2_i4! Q803I2! ERGIC!and!golgi!3(ergic3)! ERGI3!c32636_g1_i1! Q16254! E2F!transcription!factor!4(E2F4)! E2F4!c97111_g1_i1! Q13233! mitogenEactivated!protein!kinase!kinase!kinase!1(MAP3K1)! M3K1!c90732_g2_i5! Q6PFM4! limb!and!neural!patterns!b(lnpb)! LNPB!c96640_g1_i1! Q9EPJ9! ADPEribosylation!factor!GTPase!activating!protein!1(Arfgap1)! ARFG1!c96458_g2_i1! P47791! glutathione!reductase(Gsr)! GSHR!
!
! 151!
c81099_g1_i1! O60885! bromodomain!containing!4(BRD4)! BRD4!c86325_g1_i2! O60906! sphingomyelin!phosphodiesterase!2(SMPD2)! NSMA!c97714_g3_i1! Q5R9G1! defective!in!cullin!neddylation!1!domain!containing!3(DCUN1D3)! DCNL3!c73218_g1_i1! Q7ZUH1! zgc:56576(zgc:56576)! CN166!c96701_g7_i2! Q6NYY9! vacuole!membrane!protein!1(vmp1)! VMP1!c77294_g1_i1! P28661! septin!4(Sept4)! 43347!c93651_g3_i3! Q8QZY6! tetraspanin!14(Tspan14)! TSN14!c95877_g6_i1! Q567E6! coenzyme!Q10B(coq10b)! CQ10B!c97429_g2_i3! Q8BHN1! taxilin!gamma(Txlng)! TXLNG!c90570_g2_i1! Q05655! protein!kinase!C!delta(PRKCD)! KPCD!c99217_g2_i2! P52789! hexokinase!2(HK2)! HXK2!c95225_g1_i2! Q6DKI1! ribosomal!protein!L7!like!1(RPL7L1)! RL7L!c57079_g1_i1! Q568P1! HD!domain!containing!3(hddc3)! MESH1!c95410_g1_i1! Q12893! transmembrane!protein!115(TMEM115)! TM115!c92171_g1_i1! P61220! eukaryotic!translation!initiation!factor!1B(EIF1B)! EIF1B!c77241_g2_i1! Q96SA4! serine!incorporator!2(SERINC2)! SERC2!c95910_g3_i2! Q6TEK3! vitamin!K!epoxide!reductase!complex,!subunit!1Elike!1(Vkorc1l1)! VKORL!
c98384_g1_i3! O73630!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!BEcells!2!(p49/p100)!S!homeolog(nfkb2.S)! NFKB2!
c72940_g3_i1! Q6TLE4! membrane!magnesium!transporter!1(mmgt1)! MMGT1!c95444_g1_i1! Q5ZJH7! cyclin!Pas1/PHO80!domain!containing!1(CNPPD1)! CNPD1!
!
! 152!
c94334_g1_i2! Q2KI00! family!with!sequence!similarity!107!member!B(FAM107B)! F107B!c99098_g1_i3! Q6NZW8! ADPEribosylation!factorElike!8Ba(arl8ba)! AR8BA!c98648_g1_i3! Q9CZT4! polymerase!(RNA)!III!(DNA!directed)!polypeptide!E(Polr3e)! RPC5!c85007_g1_i1! P51116! FMR1!autosomal!homolog!2(FXR2)! FXR2!c98358_g1_i4! Q4KMJ1! ChaC,!cation!transport!regulator!homolog!2!(E.!coli)(chac2)! CHAC2!c89559_g2_i3! P30408! transmembrane!4!L!six!family!member!1(TM4SF1)! T4S1!c94906_g1_i8! Q9Y2U8! LEM!domain!containing!3(LEMD3)! MAN1!c90602_g1_i2! E7EY42! phosphatidylserine!synthase!2(ptdss2)! PTSS2!c97834_g4_i1! P05094! actinin,!alpha!1(ACTN1)! ACTN1!c92448_g3_i3! O94913! PCF11!cleavage!and!polyadenylation!factor!subunit(PCF11)! PCF11!c29504_g1_i1! P52739! zinc!finger!protein!131(ZNF131)! ZN131!c89338_g1_i1! Q91YU8! peter!pan!homolog!(Drosophila)(Ppan)! SSF1!c92064_g2_i3! Q08BS4! enhancer!of!zeste!2!polycomb!repressive!complex!2!subunit(ezh2)! EZH2!c94025_g1_i12! P56941! NPC!intracellular!cholesterol!transporter!1(NPC1)! NPC1!c81519_g1_i2! Q9Z2E1! methylECpG!binding!domain!protein!2(Mbd2)! MBD2!c89863_g3_i1! Q80Z29! nicotinamide!phosphoribosyltransferase(Nampt)! NAMPT!c98747_g1_i4! Q62376! small!nuclear!ribonucleoprotein!70!(U1)(Snrnp70)! RU17!c90465_g1_i1! Q6P2W5! arginine!and!glutamate!rich!1(arglu1)! ARGL1!c76101_g1_i1! P48634! proline!rich!coiledEcoil!2A(PRRC2A)! PRC2A!c97843_g4_i1! B0FYY4! integrin!subunit!beta!1(ITGB1)! ITB1!c91537_g1_i2! Q9UPQ4! tripartite!motif!containing!35(TRIM35)! TRI35!
!
! 153!
c80887_g1_i5! Q14444! cell!cycle!associated!protein!1(CAPRIN1)! CAPR1!c75640_g2_i1! Q53B90! RAB43,!member!RAS!oncogene!family(Rab43)! RAB43!c99851_g2_i1! P15822! human!immunodeficiency!virus!type!I!enhancer!binding!protein!1(HIVEP1)! ZEP1!c99371_g1_i3! P17790! basigin!(Ok!blood!group)(BSG)! BASI!c91334_g2_i1! Q9NXR1! nudE!neurodevelopment!protein!1(NDE1)! NDE1!c99217_g2_i1! P52789! hexokinase!2(HK2)! HXK2!c93734_g1_i1! Q62136! protein!tyrosine!phosphatase,!nonEreceptor!type!21(Ptpn21)! PTN21!c94032_g1_i1! Q6DBY5! UEV!and!lactate/malate!dehyrogenase!domains(uevld)! UEVLD!c69368_g1_i1! Q8UVY2! BRX1,!biogenesis!of!ribosomes!S!homeolog(brix1.S)! BRX1!c93218_g1_i3! P29558! RNA!binding!motif!single!stranded!interacting!protein!1(RBMS1)! RBMS1!c87423_g2_i1! Q14765! signal!transducer!and!activator!of!transcription!4(STAT4)! STAT4!c94135_g1_i3! Q04637! eukaryotic!translation!initiation!factor!4!gamma!1(EIF4G1)! IF4G1!c96534_g1_i1! Q6NVR9! ATPase!family,!AAA!domain!containing!3A(atad3a)! ATAD3!c76472_g3_i1! Q70EL4! ubiquitin!specific!peptidase!43(USP43)! UBP43!c92173_g1_i1! Q8IVH2! forkhead!box!P4(FOXP4)! FOXP4!c95272_g2_i7! Q14697! glucosidase!II!alpha!subunit(GANAB)! GANAB!c82884_g1_i2! Q8BMB3! eukaryotic!translation!initiation!factor!4E!member!2(Eif4e2)! IF4E2!c94411_g1_i2! O95625! zinc!finger!and!BTB!domain!containing!11(ZBTB11)! ZBT11!c94448_g3_i2! Q14677! clathrin!interactor!1(CLINT1)! EPN4!c76442_g2_i1! Q5RC74! derlin!2(DERL2)! DERL2!c95217_g2_i1! Q4R8N7! stress!induced!phosphoprotein!1(STIP1)! STIP1!
!
! 154!
c80810_g2_i1! P57088! transmembrane!protein!33(TMEM33)! TMM33!c87909_g2_i2! O35344! karyopherin!(importin)!alpha!3(Kpna3)! IMA3!c78300_g1_i1! P43250! G!proteinEcoupled!receptor!kinase!6(GRK6)! GRK6!c96516_g2_i1! Q86VQ6! thioredoxin!reductase!3(TXNRD3)! TRXR3!c85479_g1_i1! Q6DEI8! coiledEcoilEhelixEcoiledEcoilEhelix!domain!containing!4a(chchd4a)! MIA40!c50428_g1_i1! O94832! myosin!ID(MYO1D)! MYO1D!c99675_g1_i1! Q5M824! SHC!adaptor!protein!1(Shc1)! SHC1!c83139_g1_i2! Q99PF5! KHEtype!splicing!regulatory!protein(Khsrp)! FUBP2!c91971_g1_i2! O12947! isoprenylcysteine!carboxyl!methyltransferase!S!homeolog(icmt.S)! ICMT!c94144_g3_i3! P54823! DEAD!(AspEGluEAlaEAsp)!box!polypeptide!6(Ddx6)! DDX6!c59164_g1_i1! Q06124! protein!tyrosine!phosphatase,!nonEreceptor!type!11(PTPN11)! PTN11!c96500_g1_i3! Q498C8! retention!in!endoplasmic!reticulum!sorting!receptor!1(Rer1)! RER1!c88053_g1_i1! Q6DEL2! cleft!lip!and!palate!associated!transmembrane!protein!1(clptm1)! CLPT1!c97758_g4_i3! Q6GPK9! TAO!kinase!2!L!homeolog(taok2.L)! TAOK2!c97068_g4_i1! Q96AG4! leucine!rich!repeat!containing!59(LRRC59)! LRC59!c95074_g4_i3! Q6Q0C0! TNF!receptor!associated!factor!7(TRAF7)! TRAF7!c86698_g1_i1! Q0VC16! MIA!family!member!3,!ER!export!factor(MIA3)! MIA3!c98017_g3_i1! Q08BA4! solute!carrier!family!38,!member!9(slc38a9)! S38A9!
c90993_g1_i1! Q7ZXZ2!UTP15,!U3!small!nucleolar!ribonucleoprotein,!homolog!L!homeolog(utp15.L)! UTP15!
c99942_g3_i3! O43592! exportin!for!tRNA(XPOT)! XPOT!
!
! 155!
c97972_g1_i2! Q5E9N0! bystin!like(BYSL)! BYST!c8263_g1_i1! Q8BMQ8! MON1!homolog!B,!secretory!traffciking!associated(Mon1b)! MON1B!c96243_g1_i2! Q9HD45! transmembrane!9!superfamily!member!3(TM9SF3)! TM9S3!c81760_g1_i2! Q8K4Y7! calcium!activated!nucleotidase!1(Cant1)! CANT1!c71638_g1_i1! P58158! betaE1,3Eglucuronyltransferase!3!(glucuronosyltransferase!I)(B3gat3)! B3GA3!c95454_g1_i1! Q9Y673! ALG5,!dolichylEphosphate!betaEglucosyltransferase(ALG5)! ALG5!c83860_g1_i2! Q4R6K2! solute!carrier!family!30!member!1(SLC30A1)! ZNT1!c94007_g1_i1! Q6DIJ4! ubiquitin!specific!peptidase!10(usp10)! UBP10!c80483_g1_i1! D3ZTX0! transmembrane!p24!trafficking!protein!7(Tmed7)! TMED7!c86037_g1_i2! Q6DBR4! timeless!interacting!protein(tipin)! TIPIN!c72598_g1_i1! Q62165! dystroglycan!1(Dag1)! DAG1!c79788_g1_i1! Q6P0D0! QKI,!KH!domain!containing,!RNA!binding!a(qkia)! QKIA!c96845_g1_i2! Q6NRZ1! UHRF1!binding!protein!1Elike!L!homeolog(uhrf1bp1l.L)! UH1BL!c91416_g1_i1! Q1JPB9! phospholipase!A2!group!III(PLA2G3)! PA2G3!c96467_g1_i1! Q6PHK6! purineErich!element!binding!protein!Bb(purbb)! PURB!
c97544_g2_i3! Q9WTK5!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!B!cells!2,!p49/p100(Nfkb2)! NFKB2!
c99098_g1_i1! Q6NZW8! ADPEribosylation!factorElike!8Ba(arl8ba)! AR8BA!c80878_g1_i4! Q9NVG8! TBC1!domain!family!member!13(TBC1D13)! TBC13!c82632_g1_i1! Q6DFA6! coenzyme!Q10A!L!homeolog(coq10a.L)! CQ10A!c92991_g2_i2! Q5M775! sperm!antigen!with!calponin!homology!and!coiledEcoil!domains!1(SPECC1)! CYTSB!
!
! 156!
c98477_g1_i1! Q9Y2X3! NOP58!ribonucleoprotein(NOP58)! NOP58!c78988_g1_i1! Q62728! protein!tyrosine!phosphatase,!nonEreceptor!type!21(Ptpn21)! PTN21!c91689_g1_i1! Q3T083! stromal!cell!derived!factor!2!like!1(SDF2L1)! SDF2L!
c82256_g1_i1! Q8VE18!smgE8!homolog,!nonsense!mediated!mRNA!decay!factor!(C.!elegans)(Smg8)! SMG8!
c89265_g1_i1! P10881! Sjogren!syndrome!antigen!B(SSB)! LA!c84535_g1_i4! P55010! eukaryotic!translation!initiation!factor!5(EIF5)! IF5!c95230_g1_i11! Q9Y616! interleukin!1!receptor!associated!kinase!3(IRAK3)! IRAK3!c79299_g1_i2! Q96CN9! GRIP!and!coiledEcoil!domain!containing!1(GCC1)! GCC1!c99736_g2_i1! O60504! sorbin!and!SH3!domain!containing!3(SORBS3)! VINEX!c88684_g1_i1! Q6DHN0! transmembrane!protein!53(tmem53)! TMM53!c97469_g2_i1! P21932! adenylate!cyclase!3(Adcy3)! ADCY3!c94968_g1_i1! Q9I9M5! frizzled!class!receptor!1!L!homeolog(fzd1.L)! FZD1!
c83033_g3_i6! Q5XGC8!tyrosine!3Emonooxygenase/tryptophan!5Emonooxygenase!activation!protein,!beta(ywhab)! 1433B!
c92449_g1_i2! P43307! signal!sequence!receptor!subunit!1(SSR1)! SSRA!c90748_g2_i3! Q63610! tropomyosin!3(Tpm3)! TPM3!c80511_g1_i1! Q9R0K7! ATPase,!Ca++!transporting,!plasma!membrane!2(Atp2b2)! AT2B2!c89234_g2_i1! O95429! BCL2!associated!athanogene!4(BAG4)! BAG4!c94153_g5_i3! Q9Z252! linE7!homolog!B,!crumbs!cell!polarity!complex!component(Lin7b)! LIN7B!c92526_g1_i4! Q6DC39! desumoylating!isopeptidase!2(desi2)! DESI2!
!
! 157!
c99643_g1_i1! Q6P5B0! ribosomal!RNA!processing!12!homolog!(S.!cerevisiae)(Rrp12)! RRP12!c70962_g2_i1! O95782! adaptor!related!protein!complex!2!alpha!1!subunit(AP2A1)! AP2A1!c86780_g1_i1! A1L244! SAC1!suppressor!of!actin!mutations!1Elike!b!(yeast)(sacm1lb)! SAC1A!c94656_g1_i3! Q66HX0! solute!carrier!family!35,!member!B1(slc35b1)! S35B1!c99245_g2_i5! Q8BJA2! solute!carrier!family!41,!member!1(Slc41a1)! S41A1!c92932_g1_i1! Q64568! ATPase!plasma!membrane!Ca2+!transporting!3(Atp2b3)! AT2B3!c80962_g1_i1! Q5ZIT5! RAB10,!member!RAS!oncogene!family(RAB10)! RAB10!c84437_g1_i1! Q9QZR5! homeodomain!interacting!protein!kinase!2(Hipk2)! HIPK2!c95360_g2_i1! Q7TN05! adaptorErelated!protein!complex!APE1,!sigma!3(Ap1s3)! AP1S3!c94684_g2_i1! P14732! lamin!B2(LMNB2)! LMNB2!c93652_g2_i1! Q7ZTY7! unconventional!SNARE!in!the!ER!1!homolog!(S.!cerevisiae)(use1)! USE1!c84881_g1_i1! Q4ZIN3! transmembrane!protein!259(TMEM259)! MBRL!c86472_g1_i2! Q62406! interleukinE1!receptorEassociated!kinase!1(Irak1)! IRAK1!c83763_g1_i1! Q5ZJH9! dyskerin!pseudouridine!synthase!1(DKC1)! DKC1!c92366_g1_i4! P49585! phosphate!cytidylyltransferase!1,!choline,!alpha(PCYT1A)! PCY1A!c89652_g3_i2! Q6ZM28! solute!carrier!family!48!(heme!transporter),!member!1a(slc48a1a)! HRG1B!c98606_g1_i2! Q92538! golgi!brefeldin!A!resistant!guanine!nucleotide!exchange!factor!1(GBF1)! GBF1!c97971_g1_i1! Q4R588! HSPA!(Hsp70)!binding!protein!1(HSPBP1)! HPBP1!c91675_g2_i5! Q61470! CD37!antigen(Cd37)! CD37!c93938_g1_i1! A5PF10! neuraminidase!1(NEU1)! NEUR1!c82595_g1_i1! Q3V209! transmembrane!and!ubiquitinElike!domain!containing!2(Tmub2)! TMUB2!
!
! 158!
c78660_g1_i3! Q9CQX5! claudin!domain!containing!1(Cldnd1)! CLDN1!c96329_g1_i7! Q0VC16! MIA!family!member!3,!ER!export!factor(MIA3)! MIA3!c86435_g1_i1! Q9DBG7! signal!recognition!particle!receptor!('docking!protein')(Srpr)! SRPR!c92930_g1_i4! Q9Z2Q1! SEC31!homolog!A,!COPII!coat!complex!component(Sec31a)! SC31A!c99763_g2_i1! Q08174! protocadherin!1(PCDH1)! PCDH1!c83241_g1_i1! Q5E9E4! signal!sequence!receptor!subunit!2(SSR2)! SSRB!c60339_g1_i1! Q9JLG8! calpain!15(Capn15)! CAN15!c91092_g3_i1! Q8IZP0! abl!interactor!1(ABI1)! ABI1!c75188_g1_i2! O35185! basic!helixEloopEhelix!family,!member!e40(Bhlhe40)! BHE40!c85050_g3_i1! Q8QGW7! lipopolysaccharide!induced!TNF!factor(LITAF)! LITAF!c94842_g1_i4! Q90XF2! protein!kinase!C,!iota(prkci)! KPCI!c88113_g1_i1! Q1L911! nurim!(nuclear!envelope!membrane!protein(nrm)! NRM!c98868_g3_i2! Q91YN5! UDPENEacetylglucosamine!pyrophosphorylase!1(Uap1)! UAP1!c91901_g4_i1! Q78ZA7! nucleosome!assembly!protein!1Elike!4(Nap1l4)! NP1L4!c96184_g1_i1! B2ZHY2! G!proteinEcoupled!receptor!39(GPR39)! GPR39!c81199_g1_i1! Q13247! serine!and!arginine!rich!splicing!factor!6(SRSF6)! SRSF6!c77898_g1_i2! Q1L8I0! pseudouridylate!synthase!7Elike(pus7l)! PUS7L!c74074_g1_i1! Q6P5I8! Yip1!domain!family,!member!5(yipf5)! YIPF5!c97513_g1_i1! Q92537! sushi!domain!containing!6(SUSD6)! K0247!c93618_g2_i4! Q8BH98! membrane!bound!OEacyltransferase!domain!containing!1(Mboat1)! MBOA1!c88435_g1_i1! Q9BX95! sphingosineE1Ephosphate!phosphatase!1(SGPP1)! SGPP1!
!
! 159!
c53470_g1_i1! Q9BXS5! adaptor!related!protein!complex!1!mu!1!subunit(AP1M1)! AP1M1!c98182_g1_i1! O54774! adaptorErelated!protein!complex!3,!delta!1!subunit(Ap3d1)! AP3D1!c83950_g1_i1! O70377! synaptosomalEassociated!protein!23(Snap23)! SNP23!c80835_g1_i1! Q9HC07! transmembrane!protein!165(TMEM165)! TM165!c87979_g3_i1! P13797! plastin!3(PLS3)! PLST!c86902_g2_i3! Q96S16! jumonji!domain!containing!8(JMJD8)! JMJD8!c99361_g4_i1! Q9DCV6! RIKEN!cDNA!0610009O20!gene(0610009O20Rik)! DELE!c92607_g1_i1! Q96I24! far!upstream!element!binding!protein!3(FUBP3)! FUBP3!c97742_g2_i4! P32507! nectin!cell!adhesion!molecule!2(Nectin2)! PVRL2!c87345_g1_i2! Q8C159! tetratricopeptide!repeat!domain!22(Ttc22)! TTC22!c75481_g1_i1! Q9H9H4! VPS37B,!ESCRTEI!subunit(VPS37B)! VP37B!c91811_g1_i5! F1LMZ8! proteasome!26S!subunit,!nonEATPase!11(Psmd11)! PSD11!c87007_g2_i1! P20417! protein!tyrosine!phosphatase,!nonEreceptor!type!1(Ptpn1)! PTN1!
c97274_g1_i2! Q9JHT5!Alport!syndrome,!mental!retardation,!midface!hypoplasia!and!elliptocytosis!chromosomal!region!gene!1(Ammecr1)! AMMR1!
c85940_g1_i1! Q8N5C8! TGFEbeta!activated!kinase!1/MAP3K7!binding!protein!3(TAB3)! TAB3!c90405_g2_i1! Q5R660! SEC63!homolog,!protein!translocation!regulator(SEC63)! SEC63!c94842_g1_i2! Q90XF2! protein!kinase!C,!iota(prkci)! KPCI!c92008_g2_i1! Q80Z29! nicotinamide!phosphoribosyltransferase(Nampt)! NAMPT!c84536_g1_i1! Q61420! solute!carrier!family!35!(CMPEsialic!acid!transporter),!member!1(Slc35a1)! S35A1!c97082_g1_i1! Q9DAI4! zinc!finger!and!BTB!domain!containing!43(Zbtb43)! ZBT43!
!
! 160!
c76732_g1_i1! Q4V908! ubiquitinEconjugating!enzyme!E2S(ube2s)! UBE2S!
c98384_g1_i2! O73630!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!BEcells!2!(p49/p100)!S!homeolog(nfkb2.S)! NFKB2!
c94735_g2_i2! Q7ZU99! valosin!containing!protein(vcp)! TERA!c81080_g2_i1! Q640A2! heterogeneous!nuclear!ribonucleoprotein!D!like(hnrnpdl)! HNRDL!c96629_g3_i1! P51912! solute!carrier!family!1!(neutral!amino!acid!transporter),!member!5(Slc1a5)! AAAT!c91264_g1_i3! O94776! metastasis!associated!1!family!member!2(MTA2)! MTA2!c85718_g2_i1! Q9ULY5! CEtype!lectin!domain!family!4!member!E(CLEC4E)! CLC4E!c53639_g1_i1! Q61510! tripartite!motifEcontaining!25(Trim25)! TRI25!c99285_g2_i2! Q5U3Q6! thyroid!hormone!receptor!interactor!10a(trip10a)! CIP4!c79906_g1_i1! Q9JLI8! squamous!cell!carcinoma!antigen!recognized!by!T!cells!3(Sart3)! SART3!c96983_g4_i1! Q9HD67! myosin!X(MYO10)! MYO10!c81930_g1_i2! Q5R4S6! kelch!repeat!and!BTB!domain!containing!4(KBTBD4)! KBTB4!c87606_g1_i4! Q9H936! solute!carrier!family!25!member!22(SLC25A22)! GHC1!
c97274_g1_i7! Q9JHT5!Alport!syndrome,!mental!retardation,!midface!hypoplasia!and!elliptocytosis!chromosomal!region!gene!1(Ammecr1)! AMMR1!
c90576_g2_i1! Q3TJZ6! family!with!sequence!similarity!98,!member!A(Fam98a)! FA98A!c81059_g1_i2! O95433! activator!of!Hsp90!ATPase!activity!1(AHSA1)! AHSA1!c96730_g2_i1! Q684M4! kelchElike!ECHEassociated!protein!1(KEAP1)! KEAP1!c94513_g1_i2! Q9H497! torsin!family!3!member!A(TOR3A)! TOR3A!c93954_g1_i1! Q8TCJ2! STT3B,!catalytic!subunit!of!the!oligosaccharyltransferase!complex(STT3B)! STT3B!
!
! 161!
c99048_g2_i1! A0JPH4! SREBF!chaperone!S!homeolog(scap.S)! SCAP!c97544_g1_i1! O08587! nucleoporin!50(Nup50)! NUP50!c95937_g1_i4! P43378! protein!tyrosine!phosphatase,!nonEreceptor!type!9(PTPN9)! PTN9!c90893_g1_i1! Q14296! Fas!activated!serine/threonine!kinase(FASTK)! FASTK!
c79804_g1_i1! Q8VE18!smgE8!homolog,!nonsense!mediated!mRNA!decay!factor!(C.!elegans)(Smg8)! SMG8!
c91848_g1_i1! Q9ULM6! CCR4ENOT!transcription!complex!subunit!6(CNOT6)! CNOT6!c96486_g1_i1! Q3ZCH0! heat!shock!protein!family!A!(Hsp70)!member!9(HSPA9)! GRP75!c24821_g1_i1! Q9HCK0! zinc!finger!and!BTB!domain!containing!26(ZBTB26)! ZBT26!c97271_g1_i4! Q5ZJ85! preEmRNA!processing!factor!3(PRPF3)! PRPF3!c76031_g1_i1! Q3ZBF9! pyridoxal!phosphatase(PDXP)! PLPP!c92647_g1_i1! Q863I2! oxidativeEstress!responsive!1(OXSR1)! OXSR1!c83371_g1_i2! Q3UHI0! coiledEcoil!serine!rich!2(Ccser2)! CCSE2!c64522_g1_i1! O88712! CEterminal!binding!protein!1(Ctbp1)! CTBP1!c82510_g1_i2! Q9Z0Y9! nuclear!receptor!subfamily!1,!group!H,!member!3(Nr1h3)! NR1H3!c95698_g2_i3! P26818! G!proteinEcoupled!receptor!kinase!3(GRK3)! ARBK2!c98587_g1_i2! O95208! epsin!2(EPN2)! EPN2!c63745_g1_i1! Q6SPF0! sterile!alpha!motif!domain!containing!1(SAMD1)! SAMD1!c87709_g3_i4! P61589! ras!homolog!family!member!A(Rhoa)! RHOA!c99899_g2_i3! A4K2W1! SYS1,!golgi!trafficking!protein(SYS1)! SYS1!c79955_g1_i1! P50538! MAX!dimerization!protein!1(Mxd1)! MAD1!
!
! 162!
c89039_g1_i1! Q7ZWE9! cytidylate!kinase(cmpk)! KCY!c97224_g2_i1! Q6NZ07! nicalin(ncl1)! NCLN!c83096_g1_i1! Q9BUN8! derlin!1(DERL1)! DERL1!c83188_g1_i2! Q8R3Y5! RIKEN!cDNA!2310022A10!gene(2310022A10Rik)! CS047!c98753_g2_i3! Q5ZLX5! zinc!finger!RANBP2Etype!containing!2(ZRANB2)! ZRAB2!c82555_g1_i1! Q3T0T7! secretion!associated!Ras!related!GTPase!1B(SAR1B)! SAR1B!c80838_g1_i1! Q8C863! itchy,!E3!ubiquitin!protein!ligase(Itch)! ITCH!c96037_g1_i1! Q800Q5! transcription!factor!7Elike!1b!(TEcell!specific,!HMGEbox)(tcf7l1b)! T7L1B!c91587_g2_i7! Q08334! interleukin!10!receptor!subunit!beta(IL10RB)! I10R2!c96353_g1_i1! Q5F486! BCL2!associated!athanogene!5(BAG5)! BAG5!c81536_g1_i3! Q07820! BCL2!family!apoptosis!regulator(MCL1)! MCL1!c86600_g3_i3! P60484! phosphatase!and!tensin!homolog(PTEN)! PTEN!c86698_g2_i1! Q0VC16! MIA!family!member!3,!ER!export!factor(MIA3)! MIA3!c84681_g2_i2! Q5PQ53! pentaEEFEhand!domain!containing!1!L!homeolog(pef1.L)! PEF1!c70499_g1_i1! Q7ZV43! toll!interacting!protein(tollip)! TOLIP!c90070_g1_i2! A3KPA3! NEacetyltransferase!15!(GCN5Erelated,!putative)(nat15)! NAA60!c96954_g2_i2! Q91VX2! ubiquitinEassociated!protein!2(Ubap2)! UBAP2!c99365_g3_i1! Q93073! SECIS!binding!protein!2!like(SECISBP2L)! SBP2L!c75162_g1_i2! Q96D70! R3H!domain!containing!4(R3HDM4)! R3HD4!c91826_g3_i1! O09030! interleukin!13!receptor,!alpha!1(Il13ra1)! I13R1!c90637_g2_i5! Q96HL8! SH3!and!SYLF!domain!containing!1(SH3YL1)! SH3Y1!
!
! 163!
c77734_g1_i2! P49138! MAP!kinaseEactivated!protein!kinase!2(Mapkapk2)! MAPK2!c89474_g1_i3! Q6ICB0! desumoylating!isopeptidase!1(DESI1)! DESI1!c79960_g1_i1! Q60865! cell!cycle!associated!protein!1(Caprin1)! CAPR1!c91587_g2_i9! Q08334! interleukin!10!receptor!subunit!beta(IL10RB)! I10R2!
c88479_g1_i5! Q9DB05!NEethylmaleimide!sensitive!fusion!protein!attachment!protein!alpha(Napa)! SNAA!
c83347_g1_i4! O60232! Sjogren!syndrome/scleroderma!autoantigen!1(SSSCA1)! SSA27!c70234_g1_i1! Q1LZB6! cell!cycle!associated!protein!1(CAPRIN1)! CAPR1!c91697_g4_i2! Q2T9W6! LRR!binding!FLII!interacting!protein!2(LRRFIP2)! LRRF2!c87970_g3_i2! Q12797! aspartate!betaEhydroxylase(ASPH)! ASPH!c82264_g1_i1! Q5R6Q7! sorting!nexin!16(SNX16)! SNX16!c93710_g4_i1! Q5XGY1! TSR1,!20S!rRNA!accumulation,!homolog!L!homeolog(tsr1.L)! TSR1!c93445_g4_i1! P23634! ATPase!plasma!membrane!Ca2+!transporting!4(ATP2B4)! AT2B4!c98184_g2_i4! Q6DDG2! KIAA2013!S!homeolog(kiaa2013.S)! K2013!
c93341_g1_i3! Q80VC9!calmodulin!regulated!spectrinEassociated!protein!family,!member!3(Camsap3)! CAMP3!
c87717_g1_i1! Q6MG08! ATP!binding!cassette!subfamily!F!member!1(Abcf1)! ABCF1!c99285_g2_i1! Q5U3Q6! thyroid!hormone!receptor!interactor!10a(trip10a)! CIP4!
c67909_g1_i1! Q8BGT9!UDPENEacetylEalphaEDEgalactosamine:polypeptide!NEacetylgalactosaminyltransferase!12(Galnt12)! GLT12!
c88187_g6_i1! Q9Y6Q9! nuclear!receptor!coactivator!3(NCOA3)! NCOA3!
!
! 164!
c89338_g1_i2! Q91YU8! peter!pan!homolog!(Drosophila)(Ppan)! SSF1!
c98940_g1_i4! Q6NZN1!peroxisome!proliferative!activated!receptor,!gamma,!coactivatorErelated!1(Pprc1)! PPRC1!
c94456_g1_i1! Q802W4! nucleolar!protein!10(nol10)! NOL10!c87057_g1_i1! O43615! translocase!of!inner!mitochondrial!membrane!44(TIMM44)! TIM44!c81489_g1_i1! A0JNG0! transmembrane!protein!168(TMEM168)! TM168!c85841_g1_i2! Q0II25! POP7!homolog,!ribonuclease!P/MRP!subunit(POP7)! POP7!c98170_g1_i1! O08587! nucleoporin!50(Nup50)! NUP50!c95074_g4_i4! Q6Q0C0! TNF!receptor!associated!factor!7(TRAF7)! TRAF7!c67776_g1_i1! Q15811! intersectin!1(ITSN1)! ITSN1!c86293_g1_i1! P39429! TNF!receptorEassociated!factor!2(Traf2)! TRAF2!c87338_g1_i2! Q7SYN5! retinoid!x!receptor,!beta!a(rxrba)! RXRBA!c87991_g1_i5! Q8IVT5! kinase!suppressor!of!ras!1(KSR1)! KSR1!c98167_g1_i1! P16435! cytochrome!p450!oxidoreductase(POR)! NCPR!c91661_g1_i2! P09131! solute!carrier!family!10!member!3(SLC10A3)! P3!c86393_g1_i1! P38657! protein!disulfide!isomerase!family!A!member!3(PDIA3)! PDIA3!c92904_g1_i2! Q9HD15! steroid!receptor!RNA!activator!1(SRA1)! SRA1!c99644_g2_i2! Q9ERH7! homeodomain!interacting!protein!kinase!3(Hipk3)! HIPK3!c73818_g1_i2! A6QLR3! family!with!sequence!similarity!175!member!B(FAM175B)! F175B!c75676_g1_i1! Q08CA1! zgc:153343(zgc:153343)! GDPP1!c80479_g2_i1! Q5BJT2! ubiquitinElike!3(Ubl3)! UBL3!
!
! 165!
c93333_g1_i2! Q8VE04! MOB!kinase!activator!3B(Mob3b)! MOB3B!c92710_g1_i2! P52272! heterogeneous!nuclear!ribonucleoprotein!M(HNRNPM)! HNRPM!c96700_g5_i1! Q9NRR5! ubiquilin!4(UBQLN4)! UBQL4!c96237_g2_i1! Q5TM64! chromosome!4!open!reading!frame,!human!C6orf136(C4H6orf136)! CF136!c72136_g1_i1! Q07352! ZFP36!ring!finger!protein!like!1(ZFP36L1)! TISB!c94641_g2_i2! Q5FWR8! poliovirus!receptorErelated!4(pvrl4)! PVRL4!c85239_g1_i1! Q6P9R4! rho/rac!guanine!nucleotide!exchange!factor!(GEF)!18(Arhgef18)! ARHGI!c85836_g1_i6! Q6NWH1! WD!repeat!domain!32(wdr32)! DCA10!c90440_g2_i1! Q68EL3! Bet1!golgi!vesicular!membrane!trafficking!proteinElike(bet1l)! BET1L!c98586_g1_i5! A1L1G1! epithelial!splicing!regulatory!protein!1(esrp1)! ESRP1!c80313_g1_i2! Q969L2! mal,!TEcell!differentiation!protein!2!(gene/pseudogene)(MAL2)! MAL2!c73511_g1_i2! Q9BQ04! RNA!binding!motif!protein!4B(RBM4B)! RBM4B!c94000_g1_i3! Q5ZLH4! transmembrane!protein!230(TMEM230)! TM230!c93860_g1_i2! Q80VA5! SH3!domain!and!tetratricopeptide!repeats!2(Sh3tc2)! S3TC2!c72289_g1_i1! Q924T2! mitochondrial!ribosomal!protein!S2(Mrps2)! RT02!c93292_g1_i1! Q1LVW0! BTB!(POZ)!domain!containing!11a(btbd11a)! BTBBA!c95247_g1_i1! Q95108! thioredoxin!2(TXN2)! THIOM!c93122_g1_i2! O94887! FERM,!ARH/RhoGEF!and!pleckstrin!domain!protein!2(FARP2)! FARP2!c95235_g1_i5! Q9WVB1! RAB6A,!member!RAS!oncogene!family(Rab6a)! RAB6A!c93513_g2_i1! Q7RTR2! NLR!family!CARD!domain!containing!3(NLRC3)! NLRC3!
!
! 166!
c64979_g1_i1! P07222!nucleophosmin!(nucleolar!phosphoprotein!B23,!numatrin)!L!homeolog(npm1.L)! NPM!
c53858_g1_i1! A7YWC8! vimentinEtype!intermediate!filament!associated!coiledEcoil!protein(VMAC)! VMAC!c78359_g1_i1! Q8JIY8! nucleolar!protein!interacting!with!the!FHA!domain!of!MKI67(nifk)! MK67I!c97758_g4_i5! Q6GPK9! TAO!kinase!2!L!homeolog(taok2.L)! TAOK2!c88428_g1_i2! Q9JJF9! signal!peptide!peptidase!like!2A(Sppl2a)! SPP2A!c93547_g1_i3! Q13217! DnaJ!heat!shock!protein!family!(Hsp40)!member!C3(DNAJC3)! DNJC3!c92141_g1_i1! Q9PTJ3! LIM!domain!only!2!(rhombotinElike!1)(lmo2)! RBTN2!c92133_g1_i1! Q9NPB0! SAYSVFN!motif!domain!containing!1(SAYSD1)! SMDC1!c99243_g2_i2! O60701! UDPEglucose!6Edehydrogenase(UGDH)! UGDH!c81153_g1_i2! Q8R050! G1!to!S!phase!transition!1(Gspt1)! ERF3A!c94373_g1_i1! Q5PPK1! brain!protein!I3(Bri3)! BRI3!c92093_g1_i3! A4IIJ3! WW!and!C2!domain!containing!1(wwc1)! KIBRA!c94606_g1_i2! P59015! vacuolar!protein!sorting!18!homolog!(S.!cerevisiae)(vps18)! VPS18!c95064_g1_i1! Q9NR45! NEacetylneuraminate!synthase(NANS)! SIAS!c79585_g1_i1! Q9GMB0! ribophorin!I(RPN1)! RPN1!c94929_g1_i2! O75886! signal!transducing!adaptor!molecule!2(STAM2)! STAM2!c90949_g1_i1! O18738! dystroglycan!1(DAG1)! DAG1!c93912_g2_i4! Q76I76! slingshot!protein!phosphatase!2(SSH2)! SSH2!c99087_g2_i1! Q9ERG0! LIM!domain!and!actin!binding!1(Lima1)! LIMA1!c94836_g1_i3! Q6NWK2! adaptorErelated!protein!complex!2,!mu!1!subunit,!a(ap2m1a)! AP2MA!
!
! 167!
c73026_g1_i1! O43670! zinc!finger!protein!207(ZNF207)! ZN207!c99947_g1_i2! Q7ZWF4! ring!finger!protein!145b(rnf145b)! RN145!c91947_g1_i1! O94826! translocase!of!outer!mitochondrial!membrane!70(TOMM70)! TOM70!c89388_g2_i2! Q6NRD0! ankyrin!repeat!domain!13C!L!homeolog(ankrd13c.L)! A13CA!c90812_g1_i2! P61087! ubiquitinEconjugating!enzyme!E2K(Ube2k)! UBE2K!c97424_g1_i1! P08037! betaE1,4Egalactosyltransferase!1(B4GALT1)! B4GT1!c95897_g1_i1! Q9DCR2! adaptorErelated!protein!complex!3,!sigma!1!subunit(Ap3s1)! AP3S1!c94394_g1_i1! Q9ULS5! transmembrane!and!coiledEcoil!domain!family!3(TMCC3)! TMCC3!c94475_g1_i2! Q68CJ9! cAMP!responsive!element!binding!protein!3!like!3(CREB3L3)! CR3L3!c97746_g1_i2! Q9D8Y8! inhibitor!of!growth!family,!member!5(Ing5)! ING5!c77324_g2_i1! Q1LV17! interferon!regulatory!factor!2!binding!protein!1(irf2bp1)! I2BP1!c88187_g5_i1! Q9Y6Q9! nuclear!receptor!coactivator!3(NCOA3)! NCOA3!c37946_g1_i1! Q62785! PDGFA!associated!protein!1(Pdap1)! HAP28!c85740_g3_i1! Q99PP9! tripartite!motifEcontaining!16(Trim16)! TRI16!c90387_g1_i3! Q5I085! protein!phosphatase!1,!catalytic!subunit,!beta!isozyme(ppp1cb)! PP1B!c64683_g1_i1! O55111! desmoglein!2(Dsg2)! DSG2!c88187_g4_i1! O09000! nuclear!receptor!coactivator!3(Ncoa3)! NCOA3!c89620_g1_i5! P70372! ELAV!(embryonic!lethal,!abnormal!vision)Elike!1!(Hu!antigen!R)(Elavl1)! ELAV1!c94231_g2_i1! Q9BXJ9! N(alpha)Eacetyltransferase!15,!NatA!auxiliary!subunit(NAA15)! NAA15!c81148_g1_i1! Q8QG61! cryptochrome!circadian!clock!1(CRY1)! CRY1!c84452_g1_i4! P15253! calreticulin(CALR)! CALR!
!
! 168!
c70617_g1_i1! Q91YL2! ring!finger!protein!126(Rnf126)! RN126!c99963_g1_i1! Q8R4G6! mannoside!acetylglucosaminyltransferase!5(Mgat5)! MGT5A!c97682_g1_i1! P41743! protein!kinase!C!iota(PRKCI)! KPCI!c93566_g2_i3! Q91VX2! ubiquitinEassociated!protein!2(Ubap2)! UBAP2!c92787_g1_i2! Q9NQU5! p21!(RAC1)!activated!kinase!6(PAK6)! PAK6!
c93993_g1_i1! Q7ZUV1!pleckstrin!homology!domain!containing,!family!F!(with!FYVE!domain)!member!2(plekhf2)! PKHF2!
c79570_g1_i1! Q645M6! Fas!associated!via!death!domain(FADD)! FADD!c91381_g6_i2! Q16760! diacylglycerol!kinase!delta(DGKD)! DGKD!c95030_g1_i2! Q0VF96! cingulin!like!1(CGNL1)! CGNL1!c96983_g1_i3! Q96EX2! ring!finger!protein,!transmembrane!2(RNFT2)! RNFT2!c93465_g2_i2! Q9H6U8! ALG9,!alphaE1,2Emannosyltransferase(ALG9)! ALG9!c70866_g1_i3! P62840! ubiquitin!conjugating!enzyme!E2D!3!L!homeolog(ube2d3.L)! UB2D2!c70390_g2_i2! Q91WU6! zinc!finger,!DHHC!domain!containing!7(Zdhhc7)! ZDHC7!c97258_g1_i1! Q61768! kinesin!family!member!5B(Kif5b)! KINH!c90513_g1_i1! Q502M5! enhancer!of!mRNA!decapping!3!homolog!(S.!cerevisiae)(edc3)! EDC3!c99103_g3_i1! Q9NYU2! UDPEglucose!glycoprotein!glucosyltransferase!1(UGGT1)! UGGG1!c90266_g1_i1! Q8VI63! MOB!kinase!activator!2(Mob2)! MOB2!c97059_g1_i3! Q8BFW4! tripartite!motifEcontaining!65(Trim65)! TRI65!c91658_g1_i4! Q8K385! ferricEchelate!reductase!1(Frrs1)! FRRS1!c93912_g2_i3! Q76I76! slingshot!protein!phosphatase!2(SSH2)! SSH2!
!
! 169!
c98036_g1_i2! Q8K4K4! tribbles!pseudokinase!1(Trib1)! TRIB1!c71452_g1_i1! Q8UVQ4! zinc!finger!and!BTB!domain!containing!33!S!homeolog(zbtb33.S)! KAISO!c92815_g1_i1! Q7SXV2! AE!binding!protein!2(aebp2)! AEBP2!c98984_g4_i4! O14976! cyclin!G!associated!kinase(GAK)! GAK!c88005_g3_i2! Q6NYB7! RAB1A,!member!RAS!oncogene!family(Rab1a)! RAB1A!c95833_g1_i1! O75558! syntaxin!11(STX11)! STX11!c93813_g1_i5! Q6P9U4! PRELI!domain!containing!3B(Prelid3b)! SLMO2!c78666_g1_i2! Q9Z0X0! CDC42!effector!protein!(Rho!GTPase!binding)!5(Cdc42ep5)! BORG3!c84668_g1_i1! Q68EQ9! vacuole!membrane!protein!1(vmp1)! VMP1!c90031_g2_i3! Q6NRS2! PQ!loop!repeat!containing!1,!gene!1!L!homeolog(pqlc1.1.L)! PQLC1!c87181_g1_i1! P52789! hexokinase!2(HK2)! HXK2!c77241_g1_i1! Q9QZI8! serine!incorporator!1(Serinc1)! SERC1!c92764_g1_i3! A4D1S5! RAB19,!member!RAS!oncogene!family(RAB19)! RAB19!c92077_g1_i1! Q08BB1! G!elongation!factor,!mitochondrial!1(gfm1)! EFGM!c85163_g2_i1! Q5U316! RAB35,!member!RAS!oncogene!family(Rab35)! RAB35!c84933_g1_i1! Q5XH12! DEAHEbox!helicase!32!(putative)!L!homeolog(dhx32.L)! DHX32!c83824_g1_i2! Q63665! upstream!transcription!factor!2,!cEfos!interacting(Usf2)! USF2!c83096_g1_i2! Q9BUN8! derlin!1(DERL1)! DERL1!c99942_g1_i1! Q5SPJ8! exportin,!tRNA!(nuclear!export!receptor!for!tRNAs)(xpot)! XPOT!c89468_g1_i2! Q3ZBG9! phospholipid!scramblase!1(PLSCR1)! PLS2!c94292_g5_i2! Q1RMU2! CYLD!lysine!63!deubiquitinase(CYLD)! CYLD!
!
! 170!
c86447_g1_i2! Q8CFN2! cell!division!cycle!42(Cdc42)! CDC42!c92720_g2_i1! P61967! adaptor!protein!complex!APE1,!sigma!1(Ap1s1)! AP1S1!c96786_g1_i1! Q8C2Q3! RNA!binding!motif!protein!14(Rbm14)! RBM14!c94323_g1_i1! O43520! ATPase!phospholipid!transporting!8B1(ATP8B1)! AT8B1!c83127_g1_i1! Q60737! casein!kinase!2,!alpha!1!polypeptide(Csnk2a1)! CSK21!c86433_g1_i15! P30352! serine/arginineErich!splicing!factor!2(SRSF2)! SRSF2!c74619_g2_i1! P11506! ATPase!plasma!membrane!Ca2+!transporting!2(Atp2b2)! AT2B2!c81904_g3_i2! Q6ZN28! MACC1,!MET!transcriptional!regulator(MACC1)! MACC1!c96388_g1_i1! Q9H422! homeodomain!interacting!protein!kinase!3(HIPK3)! HIPK3!c76187_g1_i1! Q08334! interleukin!10!receptor!subunit!beta(IL10RB)! I10R2!c100060_g1_i1! Q5T4S7! ubiquitin!protein!ligase!E3!component!nErecognin!4(UBR4)! UBR4!c94330_g1_i2! Q8NBP0! tetratricopeptide!repeat!domain!13(TTC13)! TTC13!c77296_g1_i3! O96013! p21!(RAC1)!activated!kinase!4(PAK4)! PAK4!c86278_g1_i1! Q3U8K7! lysine!methyltransferase!5B(Kmt5b)! SV421!c75180_g1_i1! Q6AYY8! solute!carrier!family!33!member!1(Slc33a1)! ACATN!c85353_g1_i1! Q9QYN5! BEcell!CLL/lymphoma!10(Bcl10)! BCL10!c67750_g1_i1! Q96FX8! PERP,!TP53!apoptosis!effector(PERP)! PERP!c96168_g1_i2! O70496! chloride!channel,!voltageEsensitive!7(Clcn7)! CLCN7!c95650_g1_i6! Q6PFP6! NADPH!dependent!diflavin!oxidoreductase!1(ndor1)! NDOR1!c82410_g1_i2! Q9NZ09! ubiquitin!associated!protein!1(UBAP1)! UBAP1!c77753_g2_i1! Q13404! ubiquitin!conjugating!enzyme!E2!V1(UBE2V1)! UB2V1!
!
! 171!
c98060_g2_i1! Q5R478! adaptorErelated!protein!complex!3,!mu!1!subunit(AP3M1)! AP3M1!c95093_g4_i1! Q2HJ94! DnaJ!heat!shock!protein!family!(Hsp40)!member!A2(DNAJA2)! DNJA2!c90492_g2_i1! A2RRV3! protein!associated!with!topoisomerase!II!homolog!1!(yeast)(patl1)! PATL1!c93514_g1_i2! Q9NPF5! DNA!methyltransferase!1!associated!protein!1(DMAP1)! DMAP1!c87239_g2_i2! Q147X3! N(alpha)Eacetyltransferase!30,!NatC!catalytic!subunit(NAA30)! NAA30!c83544_g1_i1! Q86VS8! hook!microtubule!tethering!protein!3(HOOK3)! HOOK3!c94664_g3_i1! Q8IWE5! pleckstrin!homology!and!RUN!domain!containing!M2(PLEKHM2)! PKHM2!c87093_g1_i1! O95171! sciellin(SCEL)! SCEL!c99586_g2_i1! Q8BGV9! autophagy!related!4D,!cysteine!peptidase(Atg4d)! ATG4D!c83352_g1_i1! Q9QX82! CD164!molecule(Cd164)! MUC24!c98114_g3_i10! O35737! heterogeneous!nuclear!ribonucleoprotein!H1(Hnrnph1)! HNRH1!c74848_g1_i1! Q91398! casein!kinase!2,!beta!polypeptide(csnk2b)! CSK2B!c86827_g1_i2! Q9BXS5! adaptor!related!protein!complex!1!mu!1!subunit(AP1M1)! AP1M1!c94462_g2_i1! Q96I24! far!upstream!element!binding!protein!3(FUBP3)! FUBP3!c90919_g1_i1! Q5ZKN1! cyclinEdependent!kinase!9(CDK9)! CDK9!c98385_g1_i7! Q8K4C2! interleukin!17!receptor!C(Il17rc)! I17RC!c81150_g1_i1! Q6NYV9! LEO1!homolog,!Paf1/RNA!polymerase!II!complex!component(leo1)! LEO1!c70629_g1_i2! Q8VHI8! BCL2/adenovirus!E1B!interacting!protein!1(Bnip1)! SEC20!c81847_g1_i1! E1BK52! serine/threonine!kinase!10(STK10)! STK10!c85014_g1_i1! Q8K174! transmembrane!protein!60(Tmem60)! TMM60!c80877_g1_i1! Q6AY20! mannoseE6Ephosphate!receptor,!cation!dependent(M6pr)! MPRD!
!
! 172!
c88266_g1_i2! Q9DBI0! transmembrane!serine!protease!6(Tmprss6)! TMPS6!c94577_g1_i2! Q6P6X9! nucleoporin!35(nup35)! NUP53!c80447_g1_i1! Q803E1! nuclear!cap!binding!subunit!3(ncbp3)! CQ085!c96887_g1_i1! O35052! CDPEdiacylglycerol!synthase!1(Cds1)! CDS1!c98659_g1_i3! P22892! adaptor!protein!complex!APE1,!gamma!1!subunit(Ap1g1)! AP1G1!c69863_g1_i1! Q0VFV6! VCPEinteracting!membrane!selenoprotein(vimp)! SELS!c91587_g2_i2! P33896! interferon!(alpha!and!beta)!receptor!1(Ifnar1)! INAR1!c87353_g1_i1! Q9UM82! spermatogenesis!associated!2(SPATA2)! SPAT2!
c88501_g2_i1! Q6PEH1!KDEL!(LysEAspEGluELeu)!endoplasmic!reticulum!protein!retention!receptor!2a(kdelr2a)! ERD22!
c87933_g1_i1! O76080! zinc!finger!AN1Etype!containing!5(ZFAND5)! ZFAN5!c89620_g1_i4! P70372! ELAV!(embryonic!lethal,!abnormal!vision)Elike!1!(Hu!antigen!R)(Elavl1)! ELAV1!c94172_g1_i1! Q32NM7! immunoglobulinElike!domain!containing!receptor!1!L!homeolog(ildr1.L)! ILDR1!c56468_g1_i1! O75529! TATAEbox!binding!protein!associated!factor!5!like(TAF5L)! TAF5L!c80811_g1_i1! O60701! UDPEglucose!6Edehydrogenase(UGDH)! UGDH!c94186_g2_i2! Q00537! cyclin!dependent!kinase!17(CDK17)! CDK17!c87268_g1_i1! O18734! protein!phosphatase!1!regulatory!inhibitor!subunit!14A(PPP1R14A)! PP14A!c98346_g1_i5! C0HBB2! CA085!protein(glmp)! NCUG1!c93338_g2_i1! P49256! lectin,!mannose!binding!2(LMAN2)! LMAN2!c94344_g2_i1! Q1KMD3! heterogeneous!nuclear!ribonucleoprotein!U!like!2(HNRNPUL2)! HNRL2!c94960_g2_i3! Q53ET0! CREB!regulated!transcription!coactivator!2(CRTC2)! CRTC2!
!
! 173!
c98659_g1_i2! O43747! adaptor!related!protein!complex!1!gamma!1!subunit(AP1G1)! AP1G1!c99366_g1_i1! Q2TBX4! heat!shock!protein!family!A!(Hsp70)!member!13(HSPA13)! HSP13!c96706_g3_i1! Q8K031! START!domain!containing!8(Stard8)! STAR8!c94214_g1_i1! Q9WV60! glycogen!synthase!kinase!3!beta(Gsk3b)! GSK3B!c97757_g4_i1! Q7SY52! serine/threonine!kinase!10(stk10)! STK10!c98609_g1_i1! Q5QQ50! xylosyltransferase!2(XYLT2)! XYLT2!c89699_g1_i1! Q7ZW16! ring!finger!protein!41(rnf41)! RNF41!c93935_g1_i1! O95197! reticulon!3(RTN3)! RTN3!c82198_g2_i1! P51147! RAB5C,!member!RAS!oncogene!family(RAB5C)! RAB5C!c90666_g1_i3! Q8BHG3! transmembrane!protein!30B(Tmem30b)! CC50B!c88569_g2_i3! Q9P0J7! potassium!channel!modulatory!factor!1(KCMF1)! KCMF1!c85109_g1_i2! P25035! tumor!protein!p53(tp53)! P53!c94798_g2_i1! Q9Z0R4! intersectin!1!(SH3!domain!protein!1A)(Itsn1)! ITSN1!c87650_g1_i5! P70289! protein!tyrosine!phosphatase,!receptor!type,!V(Ptprv)! PTPRV!c93271_g3_i2! Q9UIQ6! leucyl!and!cystinyl!aminopeptidase(LNPEP)! LCAP!c94128_g1_i2! Q8IW41! mitogenEactivated!protein!kinaseEactivated!protein!kinase!5(MAPKAPK5)! MAPK5!c94314_g2_i2! Q8NHQ8! Ras!association!domain!family!member!8(RASSF8)! RASF8!c66767_g1_i1! A2PYL6! hexokinase!2(HK2)! HXK2!c75114_g1_i2! Q8IY47! kelch!repeat!and!BTB!domain!containing!2(KBTBD2)! KBTB2!c98244_g3_i1! Q8VHE0! SEC63Elike!(S.!cerevisiae)(Sec63)! SEC63!c96794_g2_i1! Q14126! desmoglein!2(DSG2)! DSG2!
!
! 174!
c92023_g1_i1! Q9BY77! DNA!polymerase!delta!interacting!protein!3(POLDIP3)! PDIP3!c93484_g1_i3! Q13393! phospholipase!D1(PLD1)! PLD1!c87250_g1_i1! O95394! phosphoglucomutase!3(PGM3)! AGM1!c94242_g2_i1! Q15061! WD!repeat!domain!43(WDR43)! WDR43!c74231_g1_i4! Q8N5C8! TGFEbeta!activated!kinase!1/MAP3K7!binding!protein!3(TAB3)! TAB3!c81217_g1_i1! Q6PEH9! solute!carrier!family!39!(zinc!transporter),!member!10(slc39a10)! S39AA!c77064_g1_i1! Q9C0G0! zinc!finger!protein!407(ZNF407)! ZN407!c80301_g2_i2! Q03173! enabled!homolog!(Drosophila)(Enah)! ENAH!c91869_g2_i3! P40222! taxilin!alpha(TXLNA)! TXLNA!
c94832_g2_i1! O35264!plateletEactivating!factor!acetylhydrolase!1b,!catalytic!subunit!2(Pafah1b2)! PA1B2!
c74062_g1_i1! Q6PBA2! LSM12!homolog!b(lsm12b)! LS12A!c91461_g3_i2! Q7TMK9! synaptotagmin!binding,!cytoplasmic!RNA!interacting!protein(Syncrip)! HNRPQ!c98812_g1_i4! Q6IQX0! lysine!(K)Especific!demethylase!5Bb(kdm5bb)! KD5BB!c94387_g2_i3! Q96GG9! defective!in!cullin!neddylation!1!domain!containing!1(DCUN1D1)! DCNL1!c92714_g1_i6! Q3B7Z2! oxysterol!binding!protein(Osbp)! OSBP1!c98042_g2_i1! P36956! sterol!regulatory!element!binding!transcription!factor!1(SREBF1)! SRBP1!c92282_g4_i1! P51817! protein!kinase,!XElinked(PRKX)! PRKX!c98114_g3_i9! P31943! heterogeneous!nuclear!ribonucleoprotein!H1!(H)(HNRNPH1)! HNRH1!c82571_g1_i3! Q13247! serine!and!arginine!rich!splicing!factor!6(SRSF6)! SRSF6!c89206_g7_i2! P60892! phosphoribosyl!pyrophosphate!synthetase!1(Prps1)! PRPS1!
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! 175!
c88318_g1_i1! Q6NU19! protein!phosphatase!1!regulatory!subunit!26!L!homeolog(ppp1r26.L)! PPR26!c99160_g1_i1! A4FUG8! rabaptin,!RAB!GTPase!binding!effector!protein!2(RABEP2)! RABE2!c75858_g2_i1! P21869! casein!kinase!2,!alpha!prime!polypeptide(CSNK2A2)! CSK22!c90780_g1_i1! Q4U3Q4! peroxisome!proliferator!activated!receptor!gamma(PPARG)! PPARG!c93875_g2_i3! Q91192! interferonEinduced!GTPEbinding!protein!Mx(mx)! MX!c52349_g1_i1! P49790! nucleoporin!153(NUP153)! NU153!c9378_g1_i1! Q6RUV5! rasErelated!C3!botulinum!toxin!substrate!1(Rac1)! RAC1!c98138_g1_i5! Q9HD67! myosin!X(MYO10)! MYO10!c89889_g1_i1! Q90WI4! matrixEremodelling!associated!8(MXRA8)! MXRA8!c98643_g1_i3! Q14157! ubiquitin!associated!protein!2!like(UBAP2L)! UBP2L!c89236_g1_i1! Q9YH91! claudin!d(cldnd)! CLDY!
c97932_g3_i2! Q9JLV2!transient!receptor!potential!cation!channel,!subfamily!C,!member!4!associated!protein(Trpc4ap)! TP4AP!
c89695_g1_i9! Q6TXF1! arrestin!domain!containing!3(Arrdc3)! ARRD3!c75271_g2_i1! Q8BID8! FEbox!and!leucineErich!repeat!protein!14(Fbxl14)! FXL14!c95235_g1_i10! Q9WVB1! RAB6A,!member!RAS!oncogene!family(Rab6a)! RAB6A!c90046_g1_i2! P80303! nucleobindin!2(NUCB2)! NUCB2!c94554_g1_i2! Q29504! ubiquitin!like!modifier!activating!enzyme!1(UBA1)! UBA1!c75668_g1_i1! Q80W96! ironEsulfur!cluster!assembly!1(Isca1)! ISCA1!c82080_g1_i1! Q2TBU3! golgi!SNAP!receptor!complex!member!1(GOSR1)! GOSR1!c95580_g1_i4! Q7M4L6! Src!homology!2!domain!containing!F(SHF)! SHF!
!
! 176!
c89899_g3_i2! Q8BGG7! ubiquitin!associated!and!SH3!domain!containing,!B(Ubash3b)! UBS3B!c92334_g1_i1! O43390! heterogeneous!nuclear!ribonucleoprotein!R(HNRNPR)! HNRPR!c99748_g1_i1! Q15643! thyroid!hormone!receptor!interactor!11(TRIP11)! TRIPB!c90622_g1_i4! Q8C1B2! TCDDEinducible!poly(ADPEribose)!polymerase(Tiparp)! PARPT!c99010_g1_i1! P49951! clathrin!heavy!chain(CLTC)! CLH1!c91147_g1_i1! Q6DBQ8! ceramideE1Ephosphate!transfer!protein(cptp)! GLTD1!c93396_g2_i1! Q6QHF9! polyamine!oxidase(PAOX)! PAOX!c86718_g1_i1! Q8VHQ4! Rab40C,!member!RAS!oncogene!family(Rab40c)! RB40C!c92762_g1_i5! Q6P0D1! solute!carrier!family!30!(zinc!transporter),!member!6(slc30a6)! ZNT6!c90677_g3_i1! Q9UL59! zinc!finger!protein!214(ZNF214)! ZN214!c88727_g2_i1! O70551! serine/arginineErich!protein!specific!kinase!1(Srpk1)! SRPK1!c79466_g1_i1! P40826! ubiquitin!specific!peptidase!14(USP14)! UBP14!c97192_g1_i3! Q13506! NGFIEA!binding!protein!1(NAB1)! NAB1!
c86651_g1_i2! Q04861!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!BEcells!1(NFKB1)! NFKB1!
c92269_g1_i3! Q5BL35! speckleEtype!POZ!proteinElike!a(spopla)! SPOLA!c99644_g1_i1! Q9QZR5! homeodomain!interacting!protein!kinase!2(Hipk2)! HIPK2!c98724_g1_i4! Q3ZBV1! IST1,!ESCRTEIII!associated!factor(IST1)! IST1!c96329_g1_i2! Q0VC16! MIA!family!member!3,!ER!export!factor(MIA3)! MIA3!c87862_g1_i2! Q6ZNE5! autophagy!related!14(ATG14)! BAKOR!c90761_g2_i14! Q62894! extracellular!matrix!protein!1(Ecm1)! ECM1!
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! 177!
c94208_g1_i2! Q8CA71! shisa!family!member!4(Shisa4)! SHSA4!c96876_g1_i4! O57478! ferrochelatase!L!homeolog(fech.L)! HEMH!c90666_g1_i1! Q8BHG3! transmembrane!protein!30B(Tmem30b)! CC50B!
c85569_g3_i1! Q925Q3!solute!carrier!family!8!(sodium/lithium/calcium!exchanger),!member!B1(Slc8b1)! NCKX6!
c98125_g2_i1! Q69ZA1! cyclinEdependent!kinase!13(Cdk13)! CDK13!c92545_g1_i1! Q6ZQM0! ring!finger!and!FYVE!like!domain!containing!protein(Rffl)! RFFL!c96233_g1_i1! O35709! ectodermalEneural!cortex!1(Enc1)! ENC1!c88872_g1_i1! Q4R4P4! fatty!acid!2Ehydroxylase(FA2H)! FA2H!c92228_g1_i1! Q9ER41! torsin!family!1,!member!B(Tor1b)! TOR1B!c96468_g2_i1! P62341! selenoprotein!T(SELENOT)! SELT!c97188_g1_i9! Q02078! myocyte!enhancer!factor!2A(MEF2A)! MEF2A!c97296_g4_i1! Q13371! phosducin!like(PDCL)! PHLP!c89323_g1_i1! Q8IWE5! pleckstrin!homology!and!RUN!domain!containing!M2(PLEKHM2)! PKHM2!c89744_g1_i1! Q1ECZ4! cancer!susceptibility!candidate!3(casc3)! CASC3!c93312_g2_i1! B5DF89! cullin!3(Cul3)! CUL3!c80402_g1_i2! P35814! protein!phosphatase,!Mg2+/Mn2+!dependent!1A(PPM1A)! PPM1A!c97045_g1_i4! Q70EL2! ubiquitin!specific!peptidase!45(USP45)! UBP45!c96774_g3_i2! Q96HN2! adenosylhomocysteinase!like!2(AHCYL2)! SAHH3!c75603_g1_i1! Q6P135! transmembrane!and!ubiquitinElike!domain!containing!1(tmub1)! TMUB1!c98895_g1_i1! Q01613! shroom!family!member!1!L!homeolog(shroom1.L)! SHRM1!
!
! 178!
c99757_g1_i1! Q8CHN6! sphingosineE1Ephosphate!lyase!1(Sgpl1)! SGPL1!c97598_g1_i3! Q9W6C5! programmed!cell!death!6!interacting!protein!L!homeolog(pdcd6ip.L)! PDC6I!c89131_g1_i4! Q8BZS9! DEAH!(AspEGluEAlaEHis)!box!polypeptide!32(Dhx32)! DHX32!c88009_g1_i1! Q9BSE2! transmembrane!protein!79(TMEM79)! TMM79!c97060_g1_i3! Q5PQZ3! solute!carrier!family!30!(zinc!transporter),!member!9(slc30a9)! ZNT9!c97907_g2_i1! Q9C0A1! zinc!finger!homeobox!2(ZFHX2)! ZFHX2!c91611_g2_i2! Q1KME6! RAB6A,!member!RAS!oncogene!family(RAB6A)! RAB6A!c99241_g1_i1! Q96K76! ubiquitin!specific!peptidase!47(USP47)! UBP47!c97166_g1_i1! Q9H4A6! golgi!phosphoprotein!3(GOLPH3)! GOLP3!c96806_g1_i2! Q00341! high!density!lipoprotein!binding!protein(HDLBP)! VIGLN!c93503_g1_i1! Q3LGD4! RAB11!family!interacting!protein!4!(class!II)!a(rab11fip4a)! RFP4A!c81462_g2_i1! Q568F6! adenylosuccinate!synthase(adss)! PURA2!c97709_g1_i2! Q5ZMC2! myosin!IG(MYO1G)! MYO1G!c85102_g1_i1! Q9DE25! forkhead!box!C1a(foxc1a)! FXC1A!c81706_g1_i1! Q86WC4! osteopetrosis!associated!transmembrane!protein!1(OSTM1)! OSTM1!c94166_g2_i1! Q58EA2! Aly/REF!export!factor!L!homeolog(alyref.L)! THO4A!c96726_g1_i1! Q8WYQ5! DGCR8,!microprocessor!complex!subunit(DGCR8)! DGCR8!c97899_g1_i2! Q1LY46! leucine!zipperEEFEhand!containing!transmembrane!protein!1(letm1)! LETM1!c99762_g2_i2! Q66JF3! MAP!kinase!interacting!serine/threonine!kinase!1(mknk1)! MKNK1!c94400_g1_i1! E7F6T8! ubiquitin!specific!peptidase!37(usp37)! UBP37!c91333_g1_i1! Q1LUT1! enhancer!of!mRNA!decapping!4(edc4)! EDC4!
!
! 179!
c86289_g1_i1! P18654! ribosomal!protein!S6!kinase!polypeptide!3(Rps6ka3)! KS6A3!c97811_g1_i1! Q96LL9! DnaJ!heat!shock!protein!family!(Hsp40)!member!C30(DNAJC30)! DJC30!c93313_g2_i1! Q6P0U9! nucleoporin!like!2(nupl2)! NUPL2!c88528_g3_i3! Q4R4T9! RAN!binding!protein!3(RANBP3)! RANB3!c95018_g1_i1! Q08CH6! ciliogenesis!associated!TTC17!interacting!protein(catip)! CB062!c85519_g2_i2! P15311! ezrin(EZR)! EZRI!c90773_g1_i1! Q7SZC2! CSE1!chromosome!segregation!1Elike!(yeast)(cse1l)! XPO2!c99465_g1_i2! A1A5V7! transmembrane!protein!41B(tmem41b)! TM41B!c99656_g2_i3! A3KNA7! sterol!regulatory!element!binding!transcription!factor!2(srebf2)! SRBP2!c96357_g2_i2! A7Z064! 3EhydroxyE3EmethylglutarylECoA!reductase(HMGCR)! HMDH!c86998_g1_i2! Q14494! nuclear!factor,!erythroid!2!like!1(NFE2L1)! NF2L1!c89693_g2_i1! Q5U2U2! vEcrk!avian!sarcoma!virus!CT10!oncogene!homologElike(Crkl)! CRKL!c94895_g1_i1! Q49AM3! tetratricopeptide!repeat!domain!31(TTC31)! TTC31!c97478_g2_i1! Q69YN4! KIAA1429(KIAA1429)! VIR!c93860_g2_i1! Q8TF17! SH3!domain!and!tetratricopeptide!repeats!2(SH3TC2)! S3TC2!c88506_g2_i1! Q6P0B1! cugbp,!ElavElike!family!member!2(celf2)! CELF2!
c92809_g2_i2! Q9UPI3!feline!leukemia!virus!subgroup!C!cellular!receptor!family!member!2(FLVCR2)! FLVC2!
c98975_g2_i2! Q86YQ8! copine!8(CPNE8)! CPNE8!c88336_g1_i1! Q5ZMW3! apoptosis!inhibitor!5(API5)! API5!c95938_g2_i2! Q15262! protein!tyrosine!phosphatase,!receptor!type!K(PTPRK)! PTPRK!
!
! 180!
c94871_g2_i5! A2VDZ9! VAMP!associated!protein!B!and!C(VAPB)! VAPB!c96080_g1_i2! P24799! GNAS!complex!locus!L!homeolog(gnas.L)! GNAS!c98712_g1_i2! Q66HV4! coatomer!protein!complex,!subunit!beta!1(copb1)! COPB!c91729_g1_i1! Q1JQ66! solute!carrier!family!35,!member!E3(slc35e3)! S35E3!c62454_g1_i1! Q9CX56! proteasome!(prosome,!macropain)!26S!subunit,!nonEATPase,!8(Psmd8)! PSMD8!c86662_g2_i1! Q9C0A1! zinc!finger!homeobox!2(ZFHX2)! ZFHX2!c97679_g1_i1! Q9NUM3! solute!carrier!family!39!member!9(SLC39A9)! S39A9!c64585_g1_i1! Q5XIS7! ubiquitinEassociated!protein!1(Ubap1)! UBAP1!c96589_g1_i1! Q8IWT3! cullin!9(CUL9)! CUL9!c98467_g1_i1! Q9Y376! calcium!binding!protein!39(CAB39)! CAB39!c93715_g1_i4! Q86YP4! GATA!zinc!finger!domain!containing!2A(GATAD2A)! P66A!c96828_g2_i1! Q2HJ69! transmembrane!protein!251(TMEM251)! TM251!c91357_g3_i1! Q5F3W3! mitogenEactivated!protein!kinase!6(MAPK6)! MK06!c92700_g2_i1! Q8IWB9! testis!expressed!2(TEX2)! TEX2!c82153_g1_i1! Q8IWT3! cullin!9(CUL9)! CUL9!c76504_g1_i1! O54967! tyrosine!kinase,!nonEreceptor,!2(Tnk2)! ACK1!c99801_g1_i1! Q6DJ55! transforming!growth!factor!beta!regulator!4(tbrg4)! TBRG4!c69935_g2_i1! P49702! ADPEribosylation!factor!5(ARF5)! ARF5!
c98384_g1_i5! O73630!nuclear!factor!of!kappa!light!polypeptide!gene!enhancer!in!BEcells!2!(p49/p100)!S!homeolog(nfkb2.S)! NFKB2!
c96733_g1_i6! Q7Z403! transmembrane!channel!like!6(TMC6)! TMC6!
!
! 181!
c97184_g1_i1! Q3KRD5! translocase!of!outer!mitochondrial!membrane!34(Tomm34)! TOM34!c82992_g1_i1! Q8TB61! solute!carrier!family!35!member!B2(SLC35B2)! S35B2!c96245_g3_i5! Q6IQ97! RNA!binding!motif!protein!4.1(rbm4.1)! RBM41!c85728_g1_i1! Q8NBJ4! golgi!membrane!protein!1(GOLM1)! GOLM1!c96652_g1_i4! Q6DGF9! acylECoA!binding!domain!containing!4(Acbd4)! ACBD4!c97501_g2_i2! Q9EPT8! chloride!intracellular!channel!5(Clic5)! CLIC5!c91010_g3_i4! P48553! trafficking!protein!particle!complex!10(TRAPPC10)! TPC10!c97432_g3_i3! Q5E9H9! abhydrolase!domain!containing!10(ABHD10)! ABHDA!c91163_g1_i1! Q0VA82! major!facilitator!superfamily!domain!containing!8(mfsd8)! MFSD8!c96570_g1_i1! P49790! nucleoporin!153(NUP153)! NU153!c91513_g1_i2! Q5U395! CTD!nuclear!envelope!phosphatase!1a(ctdnep1a)! CNEPA!
c56702_g1_i1! P62262!tyrosine!3Emonooxygenase/tryptophan!5Emonooxygenase!activation!protein!epsilon(YWHAE)! 1433E!
c94500_g3_i1! Q7TQH0! ataxin!2Elike(Atxn2l)! ATX2L!c88751_g1_i2! A2BG43! glycolipid!transfer!protein!a(gltpa)! GLTP!c83276_g1_i1! O14907! Tax1!binding!protein!3(TAX1BP3)! TX1B3!c91077_g1_i2! Q7ZWA3! RNA!binding!motif!protein,!XElinked(rbmx)! RBMX!c87909_g2_i5! O35343! karyopherin!(importin)!alpha!4(Kpna4)! IMA4!c93984_g1_i1! Q8N4C7! syntaxin!19(STX19)! STX19!
c90448_g3_i2! Q96GM5!SWI/SNF!related,!matrix!associated,!actin!dependent!regulator!of!chromatin,!subfamily!d,!member!1(SMARCD1)! SMRD1!
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! 182!
c92522_g1_i2! P48553! trafficking!protein!particle!complex!10(TRAPPC10)! TPC10!c71767_g1_i1! Q504G0! transmembrane!protein!127(tmem127)! TM127!c86049_g1_i2! Q6P6V6! G!proteinEcoupled!receptor!108(Gpr108)! GP108!c68970_g2_i3! P05552! Adh!transcription!factor!1(Adf1)! ADF1!c92857_g1_i4! Q9DCL8! protein!phosphatase!1,!regulatory!(inhibitor)!subunit!2(Ppp1r2)! IPP2!c95240_g1_i2! Q5REG1! squamous!cell!carcinoma!antigen!recognized!by!TEcells!3(SART3)! SART3!c99664_g1_i1! Q3TZZ7! extended!synaptotagminElike!protein!2(Esyt2)! ESYT2!c94871_g2_i2! Q99JZ7! ERBB!receptor!feedback!inhibitor!1(Errfi1)! ERRFI!c98575_g2_i1! Q92545! transmembrane!protein!131(TMEM131)! TM131!c69265_g1_i1! P97825! hematological!and!neurological!expressed!sequence!1(Hn1)! HN1!c95627_g3_i2! Q6PFS7! autophagy!related!3(atg3)! ATG3!c87575_g1_i1! Q921J2! Ras!homolog!enriched!in!brain(Rheb)! RHEB!c97226_g4_i1! Q6P0G8! pleckstrin!homology!domain!containing,!family!J!member!1(plekhj1)! PKHJ1!c94464_g1_i2! P21868! casein!kinase!2,!alpha!1!polypeptide(CSNK2A1)! CSK21!c99492_g2_i1! Q60943! interleukin!17!receptor!A(Il17ra)! I17RA!c72169_g1_i2! Q921R4! DnaJ!heat!shock!protein!family!(Hsp40)!member!C14(Dnajc14)! DJC14!c91547_g1_i2! P58043! sestrin!2(Sesn2)! SESN2!c90426_g2_i1! B5X3Z6! LissencephalyE1!homolog!A(lis1a)! LIS1A!c97330_g2_i3! O46606! DDHD!domain!containing!1(DDHD1)! DDHD1!c69081_g1_i2! Q16611! BCL2!antagonist/killer!1(BAK1)! BAK!c90761_g2_i12! Q62894! extracellular!matrix!protein!1(Ecm1)! ECM1!
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! 183!
c75695_g2_i1! Q02739! gap!junction!protein,!beta!5(Gjb5)! CXB5!c96587_g3_i1! Q13542! eukaryotic!translation!initiation!factor!4E!binding!protein!2(EIF4EBP2)! 4EBP2!c83139_g1_i1! Q99PF5! KHEtype!splicing!regulatory!protein(Khsrp)! FUBP2!c97331_g4_i1! Q6NZC7! Sec23!interacting!protein(Sec23ip)! S23IP!c90799_g1_i1! Q5ZHN4! retinitis!pigmentosa!2!(XElinked!recessive)(RP2)! XRP2!c93735_g1_i1! Q2PKF4! G!protein!subunit!alpha!q(GNAQ)! GNAQ!c82957_g1_i1! Q08CL3! kelch!repeat!and!BTB!(POZ)!domain!containing!8(kbtbd8)! KBTB8!c89873_g1_i3! P31483! TIA1!cytotoxic!granule!associated!RNA!binding!protein(TIA1)! TIA1!c99094_g1_i2! O62675! interleukin!16(IL16)! IL16!c95963_g1_i2! Q91YT2! ring!finger!protein!185(Rnf185)! RN185!c93160_g1_i1! Q863Z5! interleukin!4!receptor(IL4R)! IL4RA!c91622_g1_i3! Q14839! chromodomain!helicase!DNA!binding!protein!4(CHD4)! CHD4!c96954_g3_i1! P0CH95! PHD!finger!protein!8(phf8)! PHF8!c94172_g1_i3! Q32NM7! immunoglobulinElike!domain!containing!receptor!1!L!homeolog(ildr1.L)! ILDR1!c98858_g1_i1! Q91392! retinoic!acid!receptor!gamma!a(rarga)! RARGA!c90183_g1_i2! P43690! developmentally!regulated!GTP!binding!protein!1!L!homeolog(drg1.L)! DRG1!c94712_g5_i2! Q497H0! zinc!finger,!AN1Etype!domain!3(Zfand3)! ZFAN3!c93141_g3_i4! Q29099! polypyrimidine!tract!binding!protein!1(PTBP1)! PTBP1!c91031_g1_i5! Q5YCC5! transmembrane!channel!like!7(TMC7)! TMC7!c73137_g1_i1! O15156! zinc!finger!and!BTB!domain!containing!7B(ZBTB7B)! ZBT7B!c90502_g3_i1! Q6DG60! ubiquitinEconjugating!enzyme!E2Z(ube2z)! UBE2Z!
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! 184!
c98712_g1_i1! Q66HV4! coatomer!protein!complex,!subunit!beta!1(copb1)! COPB!c56322_g1_i1! A8WFS8! postEGPI!attachment!to!proteins!3(pgap3)! PGAP3!c38483_g1_i2! Q9D0C1! ring!finger!protein!115(Rnf115)! RN115!c98085_g1_i3! Q9UMZ2! synergin!gamma(SYNRG)! SYNRG!c83426_g1_i1! Q6P2L7! cancer!susceptibility!candidate!4(Casc4)! CASC4!c98782_g1_i2! Q99K30! EPS8Elike!2(Eps8l2)! ES8L2!c72533_g1_i1! Q6AYL5! splicing!factor!3b,!subunit!4(Sf3b4)! SF3B4!c96205_g1_i1! O95625! zinc!finger!and!BTB!domain!containing!11(ZBTB11)! ZBT11!
c95749_g1_i1! Q6PH57!guanine!nucleotide!binding!protein!(G!protein),!beta!polypeptide!1a(gnb1a)! GBB1!
c83033_g4_i1! Q5PRD0!tyrosine!3Emonooxygenase/tryptophan!5Emonooxygenase!activation!protein,!beta!polypeptide!a(ywhaba)! 143BA!
c98235_g3_i4! Q5ZKJ5! major!facilitator!superfamily!domain!containing!13A(MFSD13A)! TM180!c98734_g2_i1! Q96DA2! RAB39B,!member!RAS!oncogene!family(RAB39B)! RB39B!c84592_g1_i2! F8VQB6! myosin!X(Myo10)! MYO10!c95752_g1_i1! Q8IYB7! DIS3!like!3'E5'!exoribonuclease!2(DIS3L2)! DI3L2!c81410_g1_i3! Q2KIS9! tetraspanin!8(TSPAN8)! TSN8!c83506_g2_i3! P30999! catenin!(cadherin!associated!protein),!delta!1(Ctnnd1)! CTND1!c99985_g1_i1! Q9UBV2! SEL1L!ERAD!E3!ligase!adaptor!subunit(SEL1L)! SE1L1!c93591_g2_i5! Q7ZUC2! stromal!cell!derived!factor!4(sdf4)! CAB45!c74926_g1_i1! A9YUB5! ubiquitin!related!modifier!1(URM1)! URM1!
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! 185!
c98833_g2_i1! Q13200! proteasome!26S!subunit,!nonEATPase!2(PSMD2)! PSMD2!c96346_g1_i1! Q3T1J9! MOB!kinase!activator!1A(Mob1a)! MOB1A!
c94046_g2_i1! Q6NYS8!dolichylEdiphosphooligosaccharideEEprotein!glycosyltransferase!subunit!(nonEcatalytic)(ddost)! OST48!
c95367_g3_i1! Q5R7F2! zinc!fingers!and!homeoboxes!2(ZHX2)! ZHX2!c89322_g1_i1! P50995! annexin!A11(ANXA11)! ANX11!c87416_g2_i2! Q99624! solute!carrier!family!38!member!3(SLC38A3)! S38A3!c92927_g1_i1! Q6PDE7! gammaEglutamyltransferase!6(Ggt6)! GGT6!
c94004_g1_i2! Q80VC9!calmodulin!regulated!spectrinEassociated!protein!family,!member!3(Camsap3)! CAMP3!
c95145_g1_i2! Q6DHC1! RAB18B,!member!RAS!oncogene!family(rab18b)! RB18B!c88021_g2_i1! Q9Y613! formin!homology!2!domain!containing!1(FHOD1)! FHOD1!c80492_g1_i1! Q5R9S6! tetraspanin!8(TSPAN8)! TSN8!c83888_g1_i3! O55173! 3Ephosphoinositide!dependent!protein!kinaseE1(Pdpk1)! PDPK1!c59243_g1_i1! Q9CPW4! actin!related!protein!2/3!complex,!subunit!5(Arpc5)! ARPC5!c89127_g3_i1! Q6GL11! charged!multivesicular!body!protein!4B(chmp4b)! CHM4B!c98282_g1_i3! Q1L8L6! ring!finger!protein!19B(rnf19b)! RN19B!c82510_g2_i2! Q9Z0Y9! nuclear!receptor!subfamily!1,!group!H,!member!3(Nr1h3)! NR1H3!c87590_g2_i5! P14778! interleukin!1!receptor!type!1(IL1R1)! IL1R1!c95220_g1_i1! Q05932! folylpolyglutamate!synthase(FPGS)! FOLC!c92862_g1_i4! Q922K9! fynErelated!kinase(Frk)! FRK!
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! 186!
c2299_g1_i1! Q9UMY4! sorting!nexin!12(SNX12)! SNX12!c84433_g1_i1! O00429! dynamin!1!like(DNM1L)! DNM1L!c94932_g3_i7! Q5ZL54! KIAA0907(KIAA0907)! K0907!c89812_g1_i3! Q28BQ6! transmembrane!p24!trafficking!protein!1(tmed1)! TMED1!c67870_g1_i1! Q9Z1A6! high!density!lipoprotein!binding!protein(Hdlbp)! VIGLN!c88569_g2_i1! Q9P0J7! potassium!channel!modulatory!factor!1(KCMF1)! KCMF1!c84564_g1_i2! Q9H173! SIL1!nucleotide!exchange!factor(SIL1)! SIL1!c89279_g4_i1! P50591! tumor!necrosis!factor!superfamily!member!10(TNFSF10)! TNF10!c83695_g2_i1! P18654! ribosomal!protein!S6!kinase!polypeptide!3(Rps6ka3)! KS6A3!c75294_g1_i1! Q8IWX5! sphingosineE1Ephosphate!phosphatase!2(SGPP2)! SGPP2!c92164_g1_i1! P18850! activating!transcription!factor!6(ATF6)! ATF6A!c73611_g1_i1! Q8BQS5! adiponectin!receptor!2(Adipor2)! ADR2!c93338_g2_i2! P49256! lectin,!mannose!binding!2(LMAN2)! LMAN2!c90006_g1_i1! Q7SXU0! eukaryotic!translation!initiation!factor!3,!subunit!Ja(eif3ja)! EI3JA!c97464_g1_i1! Q6MG82! prolineErich!transmembrane!protein!1(Prrt1)! PRRT1!c93220_g4_i1! Q1LYE3! zinc!finger!protein!143b(znf143b)! ZN143!c90625_g3_i1! P35278! RAB5C,!member!RAS!oncogene!family(Rab5c)! RAB5C!c92764_g1_i4! Q5R8Z8! RAB14,!member!RAS!oncogene!family(RAB14)! RAB14!c97957_g2_i2! Q08705! CCCTCEbinding!factor!(zinc!finger!protein)(CTCF)! CTCF!c89789_g1_i1! Q92542! nicastrin(NCSTN)! NICA!c88362_g1_i1! P84169! proteasome!26S!subunit,!nonEATPase!13(PSMD13)! PSD13!
!
! 187!
c89113_g2_i3! Q7SXL3! TATA!box!binding!protein(tbp)! TBP!c78700_g1_i1! Q5ZLX2! eukaryotic!translation!initiation!factor!2!subunit!alpha(EIF2S1)! IF2A!c82575_g1_i1! Q62186! signal!sequence!receptor,!delta(Ssr4)! SSRD!c99736_g2_i2! O60504! sorbin!and!SH3!domain!containing!3(SORBS3)! VINEX!c98433_g2_i1! Q99ML2! tyrosine!kinase,!nonEreceptor,!1(Tnk1)! TNK1!c95849_g2_i4! Q13131! protein!kinase!AMPEactivated!catalytic!subunit!alpha!1(PRKAA1)! AAPK1!c100062_g2_i1! Q7ZWR2! cysteinylEtRNA!synthetase!S!homeolog(cars.S)! SYCC!c82789_g3_i2! Q10567! adaptor!related!protein!complex!1!beta!1!subunit(AP1B1)! AP1B1!c79553_g1_i2! Q8JFW1! asparagine!synthetase!domain!containing!1(asnsd1)! ASND1!c93046_g1_i1! A4IGC3! Rab!interacting!lysosomal!proteinElike!2(rilpl2)! RIPL2!c94230_g1_i1! A0JNT9! coiledEcoil!domain!containing!64(Ccdc64)! BICR1!c93898_g1_i1! Q5FWF5! establishment!of!sister!chromatid!cohesion!NEacetyltransferase!1(ESCO1)! ESCO1!c96080_g1_i3! P24799! GNAS!complex!locus!L!homeolog(gnas.L)! GNAS!c73663_g1_i1! Q5XI73! Rho!GDP!dissociation!inhibitor!alpha(Arhgdia)! GDIR1!c75088_g1_i1! Q7Z7A4! PX!domain!containing!serine/threonine!kinase!like(PXK)! PXK!c92830_g4_i5! A1Z3X3! golgi!to!ER!traffic!protein!4(get4)! GET4!c92882_g1_i6! Q8K4Q7! ceramide!kinase(Cerk)! CERK1!c95814_g1_i3! P62744! adaptorErelated!protein!complex!2,!sigma!1!subunit(Ap2s1)! AP2S1!
c96190_g1_i1! Q9JLB0!membrane!protein,!palmitoylated!6!(MAGUK!p55!subfamily!member!6)(Mpp6)! MPP6!
c96421_g2_i1! Q14344! G!protein!subunit!alpha!13(GNA13)! GNA13!
!
! 188!
c98096_g1_i1! Q9H1I8! activating!signal!cointegrator!1!complex!subunit!2(ASCC2)! ASCC2!c89873_g1_i2! P31483! TIA1!cytotoxic!granule!associated!RNA!binding!protein(TIA1)! TIA1!c82797_g1_i1! Q9H0S4! DEADEbox!helicase!47(DDX47)! DDX47!c95028_g1_i1! Q8BFY9! transportin!1(Tnpo1)! TNPO1!c81202_g1_i1! Q1LUT1! enhancer!of!mRNA!decapping!4(edc4)! EDC4!c94697_g1_i1! Q15811! intersectin!1(ITSN1)! ITSN1!c90110_g1_i1! P43353! aldehyde!dehydrogenase!3!family!member!B1(ALDH3B1)! AL3B1!c95302_g1_i2! Q2TA03! ubiquitin!conjugating!enzyme!E2!J2(UBE2J2)! UB2J2!c81204_g1_i1! Q90965! RAB2A,!member!RAS!oncogene!family(RAB2A)! RAB2A!c78994_g2_i1! Q7ZXV6! CDKN2A!interacting!protein!L!homeolog(cdkn2aip.L)! CARFA!c83232_g1_i1! Q5W0V3! family!with!sequence!similarity!160!member!B1(FAM160B1)! F16B1!c65424_g1_i3! P68037! ubiquitinEconjugating!enzyme!E2L!3(Ube2l3)! UB2L3!c83841_g1_i2! Q8BLX4! solute!carrier!family!35,!member!C1(Slc35c1)! FUCT1!c83613_g3_i1! Q90WN5! REST!corepressor!1!L!homeolog(rcor1.L)! RCOR1!c99563_g1_i3! Q5RI56! optineurin(optn)! OPTN!c92640_g2_i1! Q6DCP6! dymeclin!L!homeolog(dym.L)! DYM!c98475_g1_i1! Q01613! shroom!family!member!1!L!homeolog(shroom1.L)! SHRM1!c95087_g1_i2! Q1RML4! SpiEC!transcription!factor(SPIC)! SPIC!c91583_g1_i1! Q6NZY4! zinc!finger!CCHCEtype!containing!8(ZCCHC8)! ZCHC8!c90387_g1_i2! Q5I085! protein!phosphatase!1,!catalytic!subunit,!beta!isozyme(ppp1cb)! PP1B!c88685_g1_i3! Q15637! splicing!factor!1(SF1)! SF01!
!
! 189!
c85928_g1_i1! Q9UEG4! zinc!finger!protein!629(ZNF629)! ZN629!c87051_g2_i1! Q9UMY4! sorting!nexin!12(SNX12)! SNX12!c99717_g1_i1! P54613! protein!phosphatase!2!scaffold!subunit!Abeta(PPP2R1B)! 2AAB!c96386_g1_i2! Q9R0Q9! mannoseEPEdolichol!utilization!defect!1(Mpdu1)! MPU1!c88436_g2_i2! O95721! synaptosome!associated!protein!29(SNAP29)! SNP29!c75538_g1_i1! Q15428! splicing!factor!3a!subunit!2(SF3A2)! SF3A2!c96855_g2_i1! Q9NRH2! SNF!related!kinase(SNRK)! SNRK!c98282_g1_i1! Q1L8L6! ring!finger!protein!19B(rnf19b)! RN19B!c87685_g1_i1! Q2KIB3! transmembrane!protein!101(TMEM101)! TM101!c96434_g1_i2! P78536! ADAM!metallopeptidase!domain!17(ADAM17)! ADA17!c91665_g1_i3! Q96QE2! solute!carrier!family!2!member!13(SLC2A13)! MYCT!c84646_g1_i1! Q4KLY2! FEbox!protein!46(Fbxo46)! FBX46!c83710_g2_i1! Q99611! selenophosphate!synthetase!2(SEPHS2)! SPS2!c80731_g1_i1! Q9NSB8! homer!scaffolding!protein!2(HOMER2)! HOME2!c77080_g1_i1! Q60676! protein!phosphatase!5,!catalytic!subunit(Ppp5c)! PPP5!c86184_g1_i2! Q566T0! embryonic!ectoderm!development(eed)! EED!c86142_g4_i1! Q9DDJ0! ubiquitinEconjugating!enzyme!E2Ia(ube2ia)! UBC9B!c65953_g1_i2! Q4U0S5! PAF1!homolog,!Paf1/RNA!polymerase!II!complex!component(paf1)! PAF1!c95806_g1_i1! P35605! coatomer!protein!complex!subunit!beta!2(COPB2)! COPB2!c80924_g1_i1! O77506! LIM!and!SH3!protein!1(LASP1)! LASP1!c95746_g1_i1! Q6P499! NIPA!like!domain!containing!3(NIPAL3)! NPAL3!
!
! 190!
c90694_g1_i1! O76094! signal!recognition!particle!72(SRP72)! SRP72!c96743_g1_i1! Q9H3N1! thioredoxin!related!transmembrane!protein!1(TMX1)! TMX1!c83844_g2_i2! Q7SYJ9! sperm!associated!antigen!7(spag7)! SPAG7!c99530_g4_i1! Q13439! golgin!A4(GOLGA4)! GOGA4!c91817_g1_i1! P61589! ras!homolog!family!member!A(Rhoa)! RHOA!c96159_g1_i1! Q9GZV5! WW!domain!containing!transcription!regulator!1(WWTR1)! WWTR1!c97903_g1_i1! Q2TA24! ATPase!H+!transporting!V0!subunit!b(ATP6V0B)! VATO!c95232_g1_i2! Q66HY8! pyridoxalEdependent!decarboxylase!domain!containing!1(pdxdc1)! PDXD1!c88136_g1_i1! P48454! protein!phosphatase!3!catalytic!subunit!gamma(PPP3CC)! PP2BC!c88313_g1_i1! Q86U42! poly(A)!binding!protein!nuclear!1(PABPN1)! PABP2!c97864_g4_i3! Q13772! nuclear!receptor!coactivator!4(NCOA4)! NCOA4!c95716_g1_i1! Q8IZ52! chondroitin!polymerizing!factor(CHPF)! CHSS2!c80162_g1_i1! P20339! RAB5A,!member!RAS!oncogene!family(RAB5A)! RAB5A!c97659_g1_i3! P55937! golgi!autoantigen,!golgin!subfamily!a,!3(Golga3)! GOGA3!
c92292_g2_i1! Q99595!translocase!of!inner!mitochondrial!membrane!17!homolog!A!(yeast)(TIMM17A)! TI17A!
c89674_g1_i3! P10417! B!cell!leukemia/lymphoma!2(Bcl2)! BCL2!c92714_g1_i7! Q3B7Z2! oxysterol!binding!protein(Osbp)! OSBP1!c89662_g1_i2! Q64620! protein!phosphatase!6,!catalytic!subunit(Ppp6c)! PPP6!c85817_g1_i1! Q2TA17! zinc!finger!protein!668(ZNF668)! ZN668!c88291_g2_i1! Q05512! MAP/microtubule!affinity!regulating!kinase!2(Mark2)! MARK2!
!
! 191!
c99597_g1_i4! Q80U49! centrosomal!protein!170B(Cep170b)! C170B!c98330_g1_i2! O88419! betaE1,4Egalactosyltransferase!6(B4galt6)! B4GT6!c87158_g1_i3! Q08117! aminoEterminal!enhancer!of!split(AES)! AES!c99009_g2_i3! Q6P7E4! PDZ!and!LIM!domain!7(pdlim7)! PDLI7!c79658_g1_i2! Q5EB77! RAB18,!member!RAS!oncogene!family(Rab18)! RAB18!c90213_g1_i2! O43747! adaptor!related!protein!complex!1!gamma!1!subunit(AP1G1)! AP1G1!c98906_g1_i3! Q9NYG2! zinc!finger!DHHCEtype!containing!3(ZDHHC3)! ZDHC3!c93784_g2_i1! Q86TI2! dipeptidyl!peptidase!9(DPP9)! DPP9!c89811_g1_i1! Q8R105! vacuolar!protein!sorting!37C(Vps37c)! VP37C!
c94205_g1_i2! Q5U3N0!pleckstrin!homology!domain!containing,!family!A!(phosphoinositide!binding!specific)!member!8(plekha8)! PKHA8!
c97386_g1_i2! Q56A35! ARP2!actinErelated!protein!2b!homolog!(yeast)(actr2b)! ARP2B!c96136_g1_i1! Q11204! ST3!betaEgalactoside!alphaE2,3Esialyltransferase!2(St3gal2)! SIA4B!c81535_g1_i2! Q91V17! zinc!and!ring!finger!1(Znrf1)! ZNRF1!c90754_g1_i1! Q15025! TNFAIP3!interacting!protein!1(TNIP1)! TNIP1!c93141_g2_i1! Q00438! polypyrimidine!tract!binding!protein!1(Ptbp1)! PTBP1!c98160_g1_i6! Q32KW9! immunity!related!GTPase!cinema(IRGC)! IIGP5!c94836_g1_i1! Q6NWK2! adaptorErelated!protein!complex!2,!mu!1!subunit,!a(ap2m1a)! AP2MA!c99879_g1_i1! Q6P5E8! diacylglycerol!kinase,!theta(Dgkq)! DGKQ!c76852_g1_i1! Q9QYL8! lysophospholipase!II(Lypla2)! LYPA2!c75430_g1_i1! Q92734! TRKEfused!gene(TFG)! TFG!
!
! 192!
c85656_g1_i1! P22934! TNF!receptor!superfamily!member!1A(Tnfrsf1a)! TNR1A!c92508_g1_i2! O70472! transmembrane!protein!131(Tmem131)! TM131!c77753_g1_i1! Q13404! ubiquitin!conjugating!enzyme!E2!V1(UBE2V1)! UB2V1!c97633_g1_i1! Q96MC6! major!facilitator!superfamily!domain!containing!14A(MFSD14A)! HIAT1!c99968_g1_i2! O75694! nucleoporin!155(NUP155)! NU155!c90246_g1_i1! Q99816! tumor!susceptibility!101(TSG101)! TS101!c70209_g1_i1! Q503W7! ATPase!family,!AAA!domain!containing!1b(atad1b)! ATD1B!c94445_g1_i3! Q00839! heterogeneous!nuclear!ribonucleoprotein!U(HNRNPU)! HNRPU!c89206_g6_i3! P60892! phosphoribosyl!pyrophosphate!synthetase!1(Prps1)! PRPS1!c87127_g2_i1! Q6PDL0! dynein,!cytoplasmic!1!light!intermediate!chain!2(Dync1li2)! DC1L2!c96685_g1_i3! Q922R5! SMEK!homolog!2,!suppressor!of!mek1!(Dictyostelium)(Smek2)! P4R3B!c85454_g1_i2! Q9WU49! calcium!regulated!heat!stable!protein!1(Carhsp1)! CHSP1!c86275_g1_i1! P87362! bleomycin!hydrolase(BLMH)! BLMH!c91470_g1_i4! Q61990! poly(rC)!binding!protein!2(Pcbp2)! PCBP2!c95524_g3_i5! P11387! topoisomerase!(DNA)!I(TOP1)! TOP1!c91253_g1_i1! Q6NUT7! sortilin!1a(sort1a)! SORT1!c97362_g1_i3! Q3MID3! ADPEribosylation!factor!GTPase!activating!protein!2(Arfgap2)! ARFG2!c90561_g1_i1! Q8BGD9! eukaryotic!translation!initiation!factor!4B(Eif4b)! IF4B!c93822_g3_i3! Q9Z1M4! ribosomal!protein!S6!kinase,!polypeptide!2(Rps6kb2)! KS6B2!c96900_g1_i2! Q93063! exostosin!glycosyltransferase!2(EXT2)! EXT2!c90595_g1_i2! A5D7H2! striatin!3(STRN3)! STRN3!
!
! 193!
c81114_g1_i1! Q7TQH7! lowEdensity!lipoprotein!receptorErelated!protein!10(Lrp10)! LRP10!c99697_g1_i1! Q6GQB9! ER!degradation!enhancer,!mannosidase!alphaElike!3!L!homeolog(edem3.L)! EDEM3!
c95749_g1_i2! Q6PH57!guanine!nucleotide!binding!protein!(G!protein),!beta!polypeptide!1a(gnb1a)! GBB1!
c86277_g2_i3! O88967! YME1Elike!1!(S.!cerevisiae)(Yme1l1)! YMEL1!c87663_g4_i1! Q9WUM4! coronin,!actin!binding!protein!1C(Coro1c)! COR1C!c87951_g1_i2! Q16537! protein!phosphatase!2!regulatory!subunit!B'epsilon(PPP2R5E)! 2A5E!c94735_g2_i3! Q5RCM6! suppressor!of!cytokine!signaling!6(SOCS6)! SOCS6!c94872_g2_i1! O60841! eukaryotic!translation!initiation!factor!5B(EIF5B)! IF2P!c98041_g2_i1! Q8UVK2! SPT6!homolog,!histone!chaperone(supt6h)! SPT6H!c88644_g1_i1! Q9Z254! GIPC!PDZ!domain!containing!family,!member!1(Gipc1)! GIPC1!c95345_g4_i1! Q6N021! tet!methylcytosine!dioxygenase!2(TET2)! TET2!c96549_g1_i2! A3KQV2! BRO1!domain!and!CAAX!motif!containing(brox)! BROX!c95355_g3_i2! O70404! vesicleEassociated!membrane!protein!8(Vamp8)! VAMP8!c81390_g1_i2! P23956! ATPase!H+!transporting!V0!subunit!c(ATP6V0C)! VATL!c85284_g2_i2! D4ADY9! ELOVL!fatty!acid!elongase!7(Elovl7)! ELOV7!c96371_g2_i2! Q9Y5B9! SPT16!homolog,!facilitates!chromatin!remodeling!subunit(SUPT16H)! SP16H!c84337_g1_i2! Q60HE3! NADH:ubiquinone!oxidoreductase!core!subunit!S8(NDUFS8)! NDUS8!c99127_g1_i2! Q803T2! striatin!interacting!protein!1(strip1)! STRP1!c95093_g3_i1! Q2HJ94! DnaJ!heat!shock!protein!family!(Hsp40)!member!A2(DNAJA2)! DNJA2!!
!
! 194!
Supplementary!Table!3! Enriched!Ingenuity!Canonical!Pathways!Ingenuity)Canonical)Pathways) ) 3log(p3value)) Ratio) Molecules) )
Unfolded)protein)response) 9" 0.268" PPARG,"P4HB,"MAP2K7,"DDIT3,"HSPA9,"
CEBPD,"CANX,"DNAJC3,"MAP3K5,"CEBPB,"
HSP90B1,"PDIA6,"SREBF2,"EDEM1,"ATF4"
Notch)Signaling) 6.12" 0.263" NOTCH2,"JAG2,"HES5,"APH1A,"NCSTN,"
PSEN2,"HES1,"JAG1,"NOTCH1,"HEY1"
Molecular)Mechanisms)of)Cancer) 4.61" 0.0812" PA2G4,"NCSTN,"PSEN2,"CRK,"MAP3K5,"
CDK9,"MYC,"PTK2,"CASP6,"NFKBIA,"GNA15,"
IRS2,"HIPK2,"CHEK2,"CDC25A,"ARHGEF4,"
FGFR1,"ADCY3,"RAC1,"SMAD7,"FGFR2,"
FADD,"FOS,"CCNE1,"CDKN2D,"PRKCI,"
ARHGEF16,"APH1A,"CDKN1A,"TGFB3,"
NOTCH1,"CASP7"
p53)Signaling) 4.26" 0.126" CASP6,"GADD45B,"GADD45A,"GADD45G,"
FGFR1,"COQ8A,"CDKN1A,"PERP,"FGFR2,"
IRS2,"HIPK2,"TNFRSF10A,"CHEK2,"SERPINE2"
Endoplasmic)Reticulum)Stress)Pathway) 4.1" 0.286" HSP90B1,"DDIT3,"ATF4,"DNAJC3,"MAP3K5,"
CASP7"
!
! 195!
Hypoxia)Signaling)in)the)Cardiovascular)System) 4.07" 0.147" UBE2D4,"P4HB,"HSP90B1,"NFKBIA,"UBE2A,"
CREB3L3,"UBE2V1,"UBE2K,"ATF4,"UBE2E3,"
CDC34"
RAR)Activation) 3.64" 0.0947" PBRM1,"SRA1,"NR2F2,"ADCY3,"RAC1,"
SMAD7,"MAP3K5,"SMARCA4,"CSNK2A2,"FOS,"
PRKCI,"DUSP1,"RARB,"TGFB3,"SORBS3,"
MAPKAPK2,"CARM1,"PHF10"
Small)Cell)Lung)Cancer)Signaling) 3.57" 0.129" PTK2,"MYC,"TRAF3,"CCNE1,"NFKBIA,"PA2G4,"
FGFR1,"RARB,"FGFR2,"IRS2,"PTGS2"
RAN)Signaling) 3.55" 0.294" KPNA3,"KPNA5,"KPNA4,"KPNA6,"RANGAP1"
Role)of)Tissue)Factor)in)Cancer) 3.52" 0.108" P4HB,"CTGF,"FGFR1,"EGR1,"RAC1,"FGFR2,"
HBEGF,"LIMK1,"GNA15,"F2RL1,"PDIA6,"CFL2,"
IRS2,"CYR61"
Hereditary)Breast)Cancer)Signaling) 3.38" 0.1" PBRM1,"FANCM,"GADD45B,"HDAC8,"
GADD45G,"FGFR1,"FANCG,"FGFR2,"
SMARCA4,"POLR2A,"GADD45A,"CDKN1A,"
IRS2,"CHEK2,"PHF10"
HGF)Signaling) 3.37" 0.109" PTK2,"FOS,"MAP2K7,"PRKCI,"ETS2,"CRKL,"
FGFR1,"CDKN1A,"RAC1,"FGFR2,"IRS2,"
PTGS2,"MAP3K5"
!
! 196!
Glucocorticoid)Receptor)Signaling) 3.35" 0.0754" PBRM1,"SRA1,"MAP2K7,"FGFR1,"HSPA9,"
RAC1,"FGFR2,"CEBPB,"PCK1,"SMARCA4,"
NCOA3,"FOS,"HSP90B1,"KRT8,"POLR2A,"
NFKBIA,"DUSP1,"CDKN1A,"TGFB3,"FKBP4,"
IRS2,"PTGS2,"SERPINE1,"PPP3CA,"PHF10,"
ADRB2"
Th1)and)Th2)Activation)Pathway) 3.32" 0.0919" SOCS3,"JAG2,"CXCR4,"FGFR1,"NCSTN,"
FGFR2,"PSEN2,"STAT4,"NOTCH2,"APH1A,"
GFI1,"IL10RB,"IRS2,"CD274,"JAG1,"NOTCH1,"
IFNAR1"
UDP3N3acetyl3D3galactosamine)Biosynthesis)II) 3.32" 0.364" HK1,"HK2,"PGM3,"UAP1"
FGF)Signaling) 3.31" 0.121" CRKL,"FGFR1,"CREB3L3,"RAC1,"ATF4,"
FGFR2,"CRK,"IRS2,"ITPR1,"MAP3K5,"
MAPKAPK2"
GADD45)Signaling) 3.31" 0.263" CCNE1,"GADD45B,"GADD45A,"GADD45G,"
CDKN1A"
Death)Receptor)Signaling) 3.23" 0.118" FADD,"CASP6,"MAP2K7,"NFKBIA,"TIPARP,"
TNFSF10,"PARP11,"MAP3K5,"TNFRSF10A,"
CASP7,"LIMK1"
!
! 197!
IGF31)Signaling) 3.08" 0.107" PTK2,"IGFBP6,"CSNK2A2,"SOCS3,"FOS,"
PRKCI,"CTGF,"YWHAB,"FGFR1,"FGFR2,"IRS2,"
CYR61"
Osteoarthritis)Pathway) 3.07" 0.0849" PPARG,"EPAS1,"FGFR1,"CREB3L3,"RAC1,"
SMAD7,"HES1,"CEBPB,"NKX3G2,"FADD,"
CASP6,"ATF4,"NAMPT,"PTGS2,"JAG1,"HTRA1,"
NOTCH1,"CASP7"
Neurotrophin/TRK)Signaling) 3.05" 0.12" FOS,"MAP2K7,"SPRY1,"NGFR,"FGFR1,"
CREB3L3,"ATF4,"FGFR2,"IRS2,"MAP3K5"
ATM)Signaling) 3.04" 0.112" NFKBIA,"GADD45B,"GADD45A,"GADD45G,"
RAD9A,"CREB3L3,"CDKN1A,"ATF4,"TDP1,"
CHEK2,"CDC25A"
Germ)Cell3Sertoli)Cell)Junction)Signaling) 3.03" 0.0894" TUBA1B,"MAP2K7,"FGFR1,"RAC1,"FGFR2,"
MAP3K5,"LIMK1,"PTK2,"EPN2,"CFL2,"TGFB3,"
IRS2,"ACTN4,"CLINT1,"ACTN1,"NECTIN2"
NRF23mediated)Oxidative)Stress)Response) 2.96" 0.0854" MAP2K7,"DNAJB12,"FGFR1,"DNAJA4,"FGFR2,"
DNAJC3,"MAP3K5,"CUL3,"GSR,"FOS,"
DNAJC21,"PRKCI,"UBE2K,"ATF4,"IRS2,"
CDC34,"UBE2E3"
!
! 198!
Th2)Pathway) 2.9" 0.0933" SOCS3,"JAG2,"CXCR4,"FGFR1,"FGFR2,"
NCSTN,"PSEN2,"STAT4,"NOTCH2,"APH1A,"
GFI1,"IRS2,"JAG1,"NOTCH1"
Th1)Pathway) 2.86" 0.0963" SOCS3,"FGFR1,"FGFR2,"NCSTN,"PSEN2,"
STAT4,"NOTCH2,"APH1A,"IL10RB,"IRS2,"
CD274,"NOTCH1,"IFNAR1"
ERK/MAPK)Signaling) 2.85" 0.0833" PPARG,"YWHAB,"FGFR1,"CRKL,"CREB3L3,"
RAC1,"FGFR2,"PLA2G3,"CRK,"PTK2,"MYC,"
FOS,"PRKCI,"ETS2,"DUSP1,"ATF4,"IRS2"
Ephrin)A)Signaling) 2.83" 0.133" PTK2,"CFL2,"NGFR,"FGFR1,"RAC1,"FGFR2,"
IRS2,"LIMK1"
Type)II)Diabetes)Mellitus)Signaling) 2.79" 0.0909" PPARG,"SOCS3,"MAP2K7,"SLC27A2,"FGFR1,"
FGFR2,"CEBPB,"MAP3K5,"SMPD2,"PRKCI,"
NFKBIA,"NGFR,"IRS2,"MAFA"
Huntington's)Disease)Signaling) 2.65" 0.076" CAPN5,"MAP2K7,"HDAC8,"FGFR1,"PACSIN1,"
CREB3L3,"CLTC,"HSPA9,"FGFR2,"ITPR1,"
CASP6,"PRKCI,"POLR2A,"GNA15,"ATF4,"IRS2,"
NAPA,"BET1L,"CASP7"
CD40)Signaling) 2.63" 0.114" FOS,"TRAF3,"MAP2K7,"NFKBIA,"FGFR1,"
FGFR2,"IRS2,"PTGS2,"MAPKAPK2"
!
! 199!
SAPK/JNK)Signaling) 2.63" 0.1" FADD,"MAP2K7,"DUSP8,"GADD45A,"CRKL,"
FGFR1,"RAC1,"FGFR2,"CRK,"IRS2,"MAP3K5"
Chronic)Myeloid)Leukemia)Signaling) 2.57" 0.0982" MYC,"PA2G4,"HDAC8,"CRKL,"FGFR1,"
CDKN1A,"CTBP2,"TGFB3,"FGFR2,"CRK,"IRS2"
Cell)Cycle:)G1/S)Checkpoint)Regulation) 2.52" 0.119" MYC,"CCNE1,"CDKN2D,"PA2G4,"HDAC8,"
CDKN1A,"TGFB3,"CDC25A"
Role)of)Macrophages,) ) Fibroblasts)and)Endothelial)Cells)in)
Rheumatoid)Arthritis)
2.43" 0.0688" SOCS3,"MAP2K7,"TRAF3,"PDIA3,"FGFR1,"
CREB3L3,"RAC1,"CEBPD,"IL17RC,"FGFR2,"
CEBPB,"MYC,"FOS,"PRKCI,"NFKBIA,"F2RL1,"
NGFR,"TLR6,"ATF4,"IRS2,"MAPKAPK2,"
PPP3CA"
Protein)Kinase)A)Signaling) 2.43" 0.0648" DUSP8,"PDIA3,"PTPN14,"PTPN9,"UBASH3B,"
PTK2,"PHKB,"NFKBIA,"NGFR,"PTPN1,"
PTPRZ1,"ATF4,"PGP,"PPP3CA,"CDC25A,"
YWHAB,"CREB3L3,"ADCY3,"ITPR1,"PRKCI,"
DUSP1,"TGFB3,"PDE5A,"PTGS2,"PTPN21,"
KDELR2"
IL36)Signaling) 2.42" 0.0896" CSNK2A2,"SOCS3,"FOS,"MAP2K7,"NFKBIA,"
NGFR,"FGFR1,"FGFR2,"IRS2,"CEBPB,"
MAPKAPK2,"MCL1"
!
! 200!
Prostate)Cancer)Signaling) 2.35" 0.0971" HSP90B1,"CCNE1,"NFKBIA,"PA2G4,"FGFR1,"
CREB3L3,"CDKN1A,"ATF4,"FGFR2,"IRS2"
STAT3)Pathway) 2.35" 0.0971" MYC,"SOCS3,"NGFR,"FGFR1,"CDKN1A,"
RAC1,"IL10RB,"FGFR2,"IFNAR1,"CDC25A"
Pancreatic)Adenocarcinoma)Signaling) 2.34" 0.0917" CCNE1,"PA2G4,"FGFR1,"CDKN1A,"RAC1,"
TGFB3,"HBEGF,"FGFR2,"IRS2,"PTGS2,"
NOTCH1"
Leukocyte)Extravasation)Signaling) 2.31" 0.0758" CXCR4,"FGFR1,"CRKL,"RAC1,"FGFR2,"CRK,"
CLDN6,"PTK2,"TIMP4,"PRKCI,"CLDN1,"EZR,"
IRS2,"ACTN4,"CLDN3,"ACTN1"
GDP3glucose)Biosynthesis) 2.31" 0.3" HK1,"HK2,"PGM3"
JAK/Stat)Signaling) 2.28" 0.101" STAT4,"SOCS3,"FOS,"FGFR1,"PTPN1,"
CDKN1A,"FGFR2,"IRS2,"CEBPB"
B)Cell)Receptor)Signaling) 2.27" 0.0773" PTK2,"MAP2K7,"NFKBIA,"CFL2,"INPP5F,"
BCL10,"EGR1,"FGFR1,"CREB3L3,"RAC1,"
ATF4,"FGFR2,"IRS2,"MAP3K5,"PPP3CA"
Regulation)of)the)Epithelial3Mesenchymal)Transition)Pathway) 2.25" 0.0769" MAP2K7,"ID2,"JAG2,"FGFR1,"EGR1,"NCSTN,"
FGFR2,"PSEN2,"NOTCH2,"APH1A,"TGFB3,"
IRS2,"JAG1,"NOTCH1,"CLDN3"
!
! 201!
Endothelin31)Signaling) 2.23" 0.0765" MYC,"PAFAH1B2,"FOS,"CASP6,"PRKCI,"
GNA15,"PDIA3,"FGFR1,"ADCY3,"PLA2G3,"
FGFR2,"IRS2,"ITPR1,"PTGS2,"CASP7"
Glucose)and)Glucose313phosphate)Degradation) 2.19" 0.273" HK1,"HK2,"PGM3"
D3myo3inositol)(1,)4,)5,)6)3Tetrakisphosphate)Biosynthesis) 2.17" 0.0833" SOCS3,"DUSP8,"INPP5F,"DUSP1,"NUDT3,"
PTPN1,"PPFIBP2,"SGPP1,"PPP4C,"PPP3CA,"
SACM1L,"CDC25A"
D3myo3inositol)(3,)4,)5,)6)3tetrakisphosphate)Biosynthesis) 2.17" 0.0833" SOCS3,"DUSP8,"INPP5F,"DUSP1,"NUDT3,"
PTPN1,"PPFIBP2,"SGPP1,"PPP4C,"PPP3CA,"
SACM1L,"CDC25A"
33phosphoinositide)Biosynthesis) 2.13" 0.0746" SOCS3,"DUSP8,"FGFR1,"NUDT3,"PPFIBP2,"
FGFR2,"PPP4C,"SACM1L,"INPP5F,"DUSP1,"
PTPN1,"SGPP1,"IRS2,"PPP3CA,"CDC25A"
Retinoic)acid)Mediated)Apoptosis)Signaling) 2.13" 0.113" FADD,"TIPARP,"RARB,"TNFSF10,"PARP11,"
TNFRSF10A,"IFNAR1"
VDR/RXR)Activation) 2.12" 0.103" IGFBP6,"PRKCI,"GADD45A,"CDKN1A,"HES1,"
CEBPB,"KLF4,"NCOA3"
ErbB4)Signaling) 2.12" 0.103" PRKCI,"NRG2,"APH1A,"FGFR1,"NCSTN,"
FGFR2,"PSEN2,"IRS2"
Glutathione)Redox)Reactions)II) 2.12" 0.5" GSR,"PDIA3"
!
! 202!
Role)of)PI3K/AKT)Signaling)in)the)Pathogenesis)of)Influenza) 2.08" 0.101" KPNA3,"NFKBIA,"CRKL,"FGFR1,"FGFR2,"CRK,"
IRS2,"IFNAR1"
PDGF)Signaling) 2.07" 0.0938" MYC,"CSNK2A2,"FOS,"INPP5F,"CRKL,"FGFR1,"
FGFR2,"CRK,"IRS2"
IL317A)Signaling)in)Fibroblasts) 2.07" 0.143" FOS,"NFKBIA,"CEBPD,"IL17RC,"CEBPB"
TWEAK)Signaling) 2.07" 0.143" FADD,"CASP6,"TRAF3,"NFKBIA,"CASP7"
Role)of)BRCA1)in)DNA)Damage)Response) 2.05" 0.1" FANCM,"PBRM1,"GADD45A,"FANCG,"
CDKN1A,"SMARCA4,"CHEK2,"PHF10"
Aldosterone)Signaling)in)Epithelial)Cells) 2.04" 0.0774" DNAJB12,"PDIA3,"FGFR1,"HSPA9,"FGFR2,"
DNAJC3,"DNAJC2,"ITPR1,"DNAJC21,"
HSP90B1,"PRKCI,"DUSP1,"IRS2"
Epithelial)Adherens)Junction)Signaling) 2.03" 0.08" TUBA1B,"EPN2,"NOTCH2,"MAGI1,"FGFR1,"
RAC1,"CRK,"ACTN4,"CLINT1,"NOTCH1,"
ACTN1,"NECTIN2"
Clathrin3mediated)Endocytosis)Signaling) 2.02" 0.0725" AP2M1,"PICALM,"FGFR1,"AP1M1,"CLTC,"
RAC1,"FGFR2,"AP1S1,"CSNK2A2,"ARF6,"
RAB11A,"IRS2,"AP1G1,"PPP3CA,"RAB4B"
Virus)Entry)via)Endocytic)Pathways) 1.99" 0.0862" AP1S1,"AP2M1,"PRKCI,"AP1M1,"FGFR1,"
CLTC,"RAC1,"FGFR2,"IRS2,"AP1G1"
!
! 203!
CXCR4)Signaling) 1.98" 0.076" PTK2,"FOS,"PRKCI,"GNA15,"CXCR4,"EGR1,"
FGFR1,"ADCY3,"RAC1,"FGFR2,"CRK,"IRS2,"
ITPR1"
GNRH)Signaling) 1.98" 0.076" PTK2,"FOS,"MAP2K7,"PRKCI,"GNA15,"EGR1,"
CREB3L3,"ADCY3,"RAC1,"ATF4,"HBEGF,"
ITPR1,"MAP3K5"
Adipogenesis)pathway) 1.98" 0.0821" PPARG,"NR1D2,"DDIT3,"HDAC8,"FGFR1,"
NR2F2,"CTBP2,"CEBPD,"FGFR2,"CEBPB,"
PER2"
CTLA4)Signaling)in)Cytotoxic)T)Lymphocytes) 1.98" 0.0909" AP1S1,"AP2M1,"AP1M1,"FGFR1,"CLTC,"
AP1S3,"FGFR2,"IRS2,"AP1G1"
Tumoricidal)Function)of)Hepatic)Natural)Killer)Cells) 1.98" 0.167" M6PR,"FADD,"CASP6,"CASP7"
PI3K)Signaling)in)B)Lymphocytes) 1.94" 0.0809" FOS,"NFKBIA,"PRKCI,"ATF5,"PDIA3,"BCL10,"
RAC1,"ATF4,"IRS2,"ITPR1,"PPP3CA"
EGF)Signaling) 1.92" 0.103" CSNK2A2,"FOS,"MAP2K7,"FGFR1,"FGFR2,"
IRS2,"ITPR1"
Paxillin)Signaling) 1.92" 0.084" PTK2,"ARF6,"ARF1,"FGFR1,"RAC1,"FGFR2,"
CRK,"IRS2,"ACTN4,"ACTN1"
Trehalose)Degradation)II)(Trehalase)) 1.9" 0.4" HK1,"HK2"
p38)MAPK)Signaling) 1.89" 0.0833" FADD,"MYC,"DDIT3,"DUSP1,"CREB3L3,"
TGFB3,"PLA2G3,"ATF4,"MAP3K5,"MAPKAPK2"
!
! 204!
Role)of)IL317A)in)Arthritis) 1.89" 0.101" NFKBIA,"FGFR1,"IL17RC,"FGFR2,"IRS2,"
PTGS2,"MAPKAPK2"
Regulation)of)IL32)Expression)in)Activated)and)Anergic)T)
Lymphocytes)
1.87" 0.093" FOS,"MAP2K7,"NFKBIA,"BCL10,"RAC1,"
TGFB3,"TOB1,"PPP3CA"
33phosphoinositide)Degradation) 1.87" 0.0759" SOCS3,"DUSP8,"INPP5F,"DUSP1,"NUDT3,"
PTPN1,"PPFIBP2,"SGPP1,"PPP4C,"PPP3CA,"
SACM1L,"CDC25A"
Antiproliferative)Role)of)TOB)in)T)Cell)Signaling) 1.85" 0.154" CCNE1,"TGFB3,"TOB1,"CDC34"
Lipid)Antigen)Presentation)by)CD1) 1.85" 0.154" ARF6,"AP2M1,"PDIA3,"CANX"
Estrogen3mediated)S3phase)Entry) 1.85" 0.154" MYC,"CCNE1,"CDKN1A,"CDC25A"
Aryl)Hydrocarbon)Receptor)Signaling) 1.83" 0.078" MYC,"FOS,"HSP90B1,"CCNE1,"RARB,"
CDKN1A,"TGFB3,"ALDH3B1,"NCOA3,"
SMARCA4,"CHEK2"
IL33)Signaling) 1.79" 0.0899" FOS,"PRKCI,"CRKL,"FGFR1,"RAC1,"FGFR2,"
IRS2,"PPP3CA"
Prolactin)Signaling) 1.79" 0.0899" MYC,"SOCS3,"FOS,"PRKCI,"FGFR1,"FGFR2,"
IRS2,"CEBPB"
D3myo3inositol353phosphate)Metabolism) 1.79" 0.0741" SOCS3,"DUSP8,"INPP5F,"DUSP1,"NUDT3,"
PTPN1,"PPFIBP2,"SGPP1,"PPP4C,"PPP3CA,"
SACM1L,"CDC25A"
!
! 205!
NGF)Signaling) 1.78" 0.08" NGFR,"FGFR1,"CREB3L3,"RAC1,"ATF4,"
FGFR2,"CRK,"IRS2,"MAP3K5,"SMPD2"
Sphingosine313phosphate)Signaling) 1.78" 0.08" PTK2,"CASP6,"PDIA3,"FGFR1,"ADCY3,"RAC1,"
FGFR2,"IRS2,"SMPD2,"CASP7"
Ephrin)B)Signaling) 1.76" 0.0959" PTK2,"RGS3,"GNA15,"CFL2,"CXCR4,"RAC1,"
LIMK1"
UDP3N3acetyl3D3glucosamine)Biosynthesis)II) 1.74" 0.333" PGM3,"UAP1"
Sertoli)Cell3Sertoli)Cell)Junction)Signaling) 1.74" 0.0707" TUBA1B,"MAP2K7,"RAC1,"MAP3K5,"CLDN6,"
EPN2,"CLDN1,"TGFB3,"ACTN4,"CLINT1,"
CLDN3,"ACTN1,"NECTIN2"
Reelin)Signaling)in)Neurons) 1.71" 0.087" PAFAH1B2,"ARHGEF4,"MAP2K7,"CRKL,"
ARHGEF16,"FGFR1,"FGFR2,"IRS2"
Opioid)Signaling)Pathway) 1.7" 0.0648" AP2M1,"MAP2K7,"RGS3,"GRK3,"CLTC,"
ADCY3,"CREB3L3,"RAC1,"ITPR1,"MYC,"FOSB,"
FOS,"PRKCI,"NFKBIA,"ATF4,"PPP3CA"
NF3κB)Signaling) 1.69" 0.0695" MAP2K7,"TRAF3,"FGFR1,"FGFR2,"TAB3,"
FADD,"CSNK2A2,"NFKBIA,"BCL10,"NGFR,"
TLR6,"UBE2V1,"IRS2"
LPS3stimulated)MAPK)Signaling) 1.68" 0.086" FOS,"NFKBIA,"PRKCI,"FGFR1,"RAC1,"FGFR2,"
IRS2,"MAP3K5"
!
! 206!
PEDF)Signaling) 1.68" 0.086" PPARG,"NFKBIA,"FGFR1,"RAC1,"FGFR2,"
IRS2,"PNPLA2,"CASP7"
Neuregulin)Signaling) 1.66" 0.0851" MYC,"HSP90B1,"PRKCI,"NRG2,"CRKL,"
HBEGF,"ERRFI1,"CRK"
PI3K/AKT)Signaling) 1.65" 0.0763" RHEB,"HSP90B1,"NFKBIA,"INPP5F,"YWHAB,"
CDKN1A,"GDF15,"PTGS2,"MAP3K5,"MCL1"
Tec)Kinase)Signaling) 1.64" 0.0706" PTK2,"FADD,"STAT4,"FOS,"PRKCI,"GNA15,"
GTF2I,"FGFR1,"TNFSF10,"FGFR2,"IRS2,"
TNFRSF10A"
Nitric)Oxide)Signaling)in)the)Cardiovascular)System) 1.64" 0.0796" HSP90B1,"PRKCI,"FGFR1,"PDE5A,"SLC7A1,"
FGFR2,"IRS2,"ITPR1,"ATP2A2"
Signaling)by)Rho)Family)GTPases) 1.62" 0.0635" ARHGEF4,"MAP2K7,"FGFR1,"CDC42EP5,"
RAC1,"FGFR2,"CDC42EP2,"LIMK1,"PTK2,"
FOS,"PRKCI,"GNA15,"CFL2,"EZR,"ARHGEF16,"
IRS2"
Induction)of)Apoptosis)by)HIV1) 1.62" 0.0984" FADD,"MAP2K7,"NFKBIA,"CXCR4,"NGFR,"
MAP3K5"
Actin)Cytoskeleton)Signaling) 1.6" 0.0644" PTK2,"ARHGEF4,"TIAM2,"CFL2,"EZR,"CRKL,"
FGFR1,"RAC1,"FGFR2,"CRK,"IRS2,"ACTN4,"
ARHGAP24,"ACTN1,"LIMK1"
Glycoaminoglycan3protein)Linkage)Region)Biosynthesis) 1.6" 0.286" B4GALT7,"XYLT2"
!
! 207!
Estrogen)Receptor)Signaling) 1.59" 0.0746" SRA1,"DDX5,"POLR2A,"CTBP2,"MED31,"
HNRNPD,"PCK1,"NCOA3,"CARM1,"SMARCA4"
Superpathway)of)Inositol)Phosphate)Compounds) 1.56" 0.0636" SOCS3,"DUSP8,"FGFR1,"NUDT3,"PPFIBP2,"
FGFR2,"PPP4C,"SACM1L,"INPP5F,"DUSP1,"
PTPN1,"SGPP1,"IRS2,"PPP3CA,"CDC25A"
Regulation)of)Cellular)Mechanics)by)Calpain)Protease) 1.56" 0.0952" PTK2,"CAPN5,"CCNE1,"EZR,"ACTN4,"ACTN1"
AMPK)Signaling) 1.55" 0.0648" PBRM1,"CAB39,"RAB1A,"FGFR1,"CREB3L3,"
FGFR2,"ELAVL1,"SMARCA4,"CDKN1A,"
RAB11A,"ATF4,"IRS2,"PHF10,"ADRB2"
Cyclins)and)Cell)Cycle)Regulation) 1.54" 0.0864" CCNE1,"CDKN2D,"PA2G4,"HDAC8,"CDKN1A,"
TGFB3,"CDC25A"
1433333mediated)Signaling) 1.53" 0.073" TUBA1B,"FOS,"PRKCI,"YWHAB,"PDIA3,"
FGFR1,"EDC3,"FGFR2,"IRS2,"MAP3K5"
Ephrin)Receptor)Signaling) 1.49" 0.067" PTK2,"RGS3,"SDCBP,"GNA15,"CFL2,"CXCR4,"
CRKL,"CREB3L3,"RAC1,"ATF4,"CRK,"LIMK1"
Salvage)Pathways)of)Pyrimidine)Deoxyribonucleotides) 1.49" 0.25" CDA,"TK1"
P2Y)Purigenic)Receptor)Signaling)Pathway) 1.48" 0.0714" MYC,"FOS,"PRKCI,"PDIA3,"FGFR1,"CREB3L3,"
ADCY3,"ATF4,"FGFR2,"IRS2"
RANK)Signaling)in)Osteoclasts) 1.47" 0.0784" FOS,"MAP2K7,"NFKBIA,"FGFR1,"FGFR2,"IRS2,"
MAP3K5,"PPP3CA"
Circadian)Rhythm)Signaling) 1.46" 0.118" PER1,"CREB3L3,"ATF4,"PER2"
!
! 208!
TNFR1)Signaling) 1.45" 0.1" FADD,"CASP6,"FOS,"NFKBIA,"CASP7"
Protein)Ubiquitination)Pathway) 1.45" 0.0604" UBE2D4,"DNAJC21,"PSMD11,"HSP90B1,"
DNAJB12,"UBE2A,"PSMD2,"HSPA9,"UBE2V1,"
UBE2K,"DNAJC3,"DNAJC2,"USP37,"CDC34,"
UBE2E3,"PSMD8"
Cell)Cycle:)G2/M)DNA)Damage)Checkpoint)Regulation) 1.45" 0.1" GADD45A,"YWHAB,"CDKN1A,"HIPK2,"CHEK2"
Rac)Signaling) 1.43" 0.0732" PTK2,"MAP2K7,"PRKCI,"CFL2,"FGFR1,"RAC1,"
FGFR2,"IRS2,"LIMK1"
Estrogen3Dependent)Breast)Cancer)Signaling) 1.42" 0.0814" FOS,"FGFR1,"CREB3L3,"HSD17B12,"ATF4,"
FGFR2,"IRS2"
Amyloid)Processing) 1.42" 0.098" CAPN5,"CSNK2A2,"APH1A,"NCSTN,"PSEN2"
Erythropoietin)Signaling) 1.39" 0.0805" SOCS3,"FOS,"NFKBIA,"PRKCI,"FGFR1,"
FGFR2,"IRS2"
EIF2)Signaling) 1.39" 0.0617" DDIT3,"ATF5,"FGFR1,"FGFR2,"EIF4G1,"
RPL37A,"RPS11,"MYC,"EIF3F,"RPL35,"EIF5,"
RPL21,"ATF4,"IRS2"
Macropinocytosis)Signaling) 1.39" 0.0805" ARF6,"PRKCI,"FGFR1,"RAC1,"FGFR2,"IRS2,"
ACTN4"
PTEN)Signaling) 1.39" 0.072" PTK2,"CSNK2A2,"MAGI1,"INPP5F,"NGFR,"
FGFR1,"CDKN1A,"RAC1,"FGFR2"
Phosphatidylethanolamine)Biosynthesis)II) 1.39" 0.222" PCYT2,"ETNK1"
!
! 209!
PAK)Signaling) 1.37" 0.0748" PTK2,"ARHGAP10,"CFL2,"FGFR1,"RAC1,"
FGFR2,"IRS2,"LIMK1"
Tight)Junction)Signaling) 1.36" 0.0659" FOS,"PRKCI,"CLDN1,"NGFR,"RAC1,"TGFB3,"
CLDN6,"BET1L,"NAPA,"CLDN3,"NECTIN2"
Insulin)Receptor)Signaling) 1.35" 0.068" SOCS3,"PRKCI,"INPP5F,"TRIP10,"CRKL,"
FGFR1,"PTPN1,"FGFR2,"CRK,"IRS2"
Thrombopoietin)Signaling) 1.34" 0.0845" MYC,"FOS,"PRKCI,"FGFR1,"FGFR2,"IRS2"
Renin3Angiotensin)Signaling) 1.34" 0.0703" PTK2,"FOS,"PRKCI,"FGFR1,"ADCY3,"RAC1,"
FGFR2,"IRS2,"ITPR1"
Breast)Cancer)Regulation)by)Stathmin1) 1.32" 0.0616" TUBA1B,"ARHGEF4,"CCNE1,"PRKCI,"
ARHGEF16,"FGFR1,"CDKN1A,"ADCY3,"RAC1,"
FGFR2,"IRS2,"ITPR1,"LIMK1"
IL317)Signaling) 1.31" 0.0769" FGFR1,"IL17RC,"FGFR2,"IRS2,"PTGS2,"
CEBPB,"MAPKAPK2"
IL37)Signaling)Pathway) 1.31" 0.0769" PTK2,"MYC,"FGFR1,"FGFR2,"IRS2,"CDC25A,"
MCL1"
Calcium)Transport)I) 1.3" 0.2" ATP2B3,"ATP2A2"
Amyotrophic)Lateral)Sclerosis)Signaling) 1.29" 0.0721" CAPN5,"FGFR1,"RAC1,"FGFR2,"IRS2,"
RNF19A,"CASP7,"PPP3CA"
UVA3Induced)MAPK)Signaling) 1.27" 0.0714" FOS,"TIPARP,"PDIA3,"FGFR1,"FGFR2,"
PARP11,"IRS2,"SMPD2"
!
! 210!
CD28)Signaling)in)T)Helper)Cells) 1.27" 0.0682" FOS,"NFKBIA,"BCL10,"FGFR1,"RAC1,"FGFR2,"
IRS2,"ITPR1,"PPP3CA"
April)Mediated)Signaling) 1.27" 0.103" FOS,"TRAF3,"MAP2K7,"NFKBIA"
Fcγ)Receptor3mediated)Phagocytosis)in)Macrophages)and)
Monocytes)
1.26" 0.0753" ARF6,"PRKCI,"EZR,"RAC1,"DGKB,"RAB11A,"
CRK"
GP6)Signaling)Pathway) 1.24" 0.0672" LAMB2,"PTK2,"PRKCI,"FGFR1,"RAC1,"LAMA3,"
FGFR2,"IRS2,"ITPR1"
HER32)Signaling)in)Breast)Cancer) 1.24" 0.0745" CCNE1,"PRKCI,"FGFR1,"CDKN1A,"FGFR2,"
IRS2,"MAP3K5"
ILK)Signaling) 1.23" 0.0609" PTK2,"MYC,"FOS,"CFL2,"FGFR1,"CREB3L3,"
ATF4,"FGFR2,"IRS2,"ACTN4,"PTGS2,"ACTN1"
T)Cell)Receptor)Signaling) 1.22" 0.0696" FOS,"NFKBIA,"BCL10,"FGFR1,"RAC1,"FGFR2,"
IRS2,"PPP3CA"
Myc)Mediated)Apoptosis)Signaling) 1.22" 0.0789" FADD,"MYC,"YWHAB,"FGFR1,"FGFR2,"IRS2"
Integrin)Signaling) 1.22" 0.0594" CAPN5,"ARF1,"FGFR1,"CRKL,"RAC1,"FGFR2,"
CRK,"TNK2,"PTK2,"ARF6,"IRS2,"ACTN4,"
ACTN1"
B)Cell)Activating)Factor)Signaling) 1.21" 0.0976" FOS,"TRAF3,"MAP2K7,"NFKBIA"
CCR3)Signaling)in)Eosinophils) 1.2" 0.0662" PRKCI,"CFL2,"FGFR1,"RAC1,"PLA2G3,"
FGFR2,"IRS2,"ITPR1,"LIMK1"
!
! 211!
Apoptosis)Signaling) 1.2" 0.0729" CAPN5,"CASP6,"MAP2K7,"NFKBIA,"MAP3K5,"
CASP7,"MCL1"
Role)of)Pattern)Recognition)Receptors)in)Recognition)of)Bacteria)
and)Viruses)
1.19" 0.0657" PTX3,"PRKCI,"TICAM1,"FGFR1,"TLR6,"TGFB3,"
FGFR2,"IRS2,"RIPK2"
Adrenomedullin)signaling)pathway) 1.19" 0.06" PPARG,"PTK2,"FOS,"MAP2K7,"GNA15,"PDIA3,"
FGFR1,"ADCY3,"FGFR2,"IRS2,"ITPR1,"CEBPB"
Telomerase)Signaling) 1.18" 0.0684" MYC,"HSP90B1,"HDAC8,"ETS2,"FGFR1,"
CDKN1A,"FGFR2,"IRS2"
TR/RXR)Activation) 1.17" 0.0714" KLF9,"SREBF2,"FGFR1,"FGFR2,"IRS2,"PCK1,"
NCOA3"
HMGB1)Signaling) 1.16" 0.0647" FOS,"MAP2K7,"NGFR,"FGFR1,"RAC1,"TGFB3,"
FGFR2,"IRS2,"SERPINE1"
MIF)Regulation)of)Innate)Immunity) 1.15" 0.093" FOS,"NFKBIA,"PLA2G3,"PTGS2"
Role)of)p14/p19ARF)in)Tumor)Suppression) 1.15" 0.093" FGFR1,"RAC1,"FGFR2,"IRS2"
Glycine)Biosynthesis)III) 1.14" 0.5" AGXT2"
Threonine)Degradation)II) 1.14" 0.5" GCAT"
Formaldehyde)Oxidation)II)(Glutathione3dependent)) 1.14" 0.5" ESD"
PPAR)Signaling) 1.11" 0.0693" PPARG,"FOS,"SRA1,"HSP90B1,"NFKBIA,"
NGFR,"PTGS2"
GDNF)Family)Ligand3Receptor)Interactions) 1.1" 0.0732" FOS,"FGFR1,"RAC1,"FGFR2,"IRS2,"ITPR1"
Glycogen)Degradation)II) 1.1" 0.154" PGM3,"AGL"
!
! 212!
IL39)Signaling) 1.09" 0.0889" SOCS3,"FGFR1,"FGFR2,"IRS2"
Non3Small)Cell)Lung)Cancer)Signaling) 1.08" 0.0723" PA2G4,"FGFR1,"RARB,"FGFR2,"IRS2,"ITPR1"
Melanocyte)Development)and)Pigmentation)Signaling) 1.06" 0.0673" FGFR1,"CREB3L3,"ADCY3,"ATF4,"FGFR2,"
CRK,"IRS2"
ErbB)Signaling) 1.06" 0.0673" FOS,"PRKCI,"NRG2,"FGFR1,"HBEGF,"FGFR2,"
IRS2"
Angiopoietin)Signaling) 1.06" 0.0714" PTK2,"NFKBIA,"FGFR1,"FGFR2,"CRK,"IRS2"
Role)of)Oct4)in)Mammalian)Embryonic)Stem)Cell)Pluripotency) 1.06" 0.087" CASP6,"ETS2,"NR2F2,"JARID2"
IL312)Signaling)and)Production)in)Macrophages) 1.05" 0.0616" PPARG,"STAT4,"FOS,"PRKCI,"FGFR1,"TGFB3,"
FGFR2,"IRS2,"CEBPB"
Fc)Epsilon)RI)Signaling) 1.05" 0.064" MAP2K7,"PRKCI,"INPP5F,"FGFR1,"RAC1,"
PLA2G3,"FGFR2,"IRS2"
Growth)Hormone)Signaling) 1.04" 0.0706" SOCS3,"FOS,"PRKCI,"FGFR1,"FGFR2,"IRS2"
FAK)Signaling) 1.04" 0.0667" PTK2,"CAPN5,"FGFR1,"RAC1,"FGFR2,"CRK,"
IRS2"
γ3glutamyl)Cycle) 1.04" 0.143" CHAC1,"CHAC2"
UVB3Induced)MAPK)Signaling) 1.03" 0.0758" FOS,"PRKCI,"FGFR1,"FGFR2,"IRS2"
Mitotic)Roles)of)Polo3Like)Kinase) 1.03" 0.0758" HSP90B1,"PLK3,"PLK2,"CHEK2,"CDC25A"
Leptin)Signaling)in)Obesity) 1.02" 0.0698" SOCS3,"PDIA3,"FGFR1,"ADCY3,"FGFR2,"IRS2"
Lymphotoxin)β)Receptor)Signaling) 1.01" 0.0746" TRAF3,"NFKBIA,"FGFR1,"FGFR2,"IRS2"
!
! 213!
fMLP)Signaling)in)Neutrophils) 0.993" 0.062" NFKBIA,"PRKCI,"FGFR1,"RAC1,"FGFR2,"IRS2,"
ITPR1,"PPP3CA"
Glycogen)Degradation)III) 0.988" 0.133" PGM3,"AGL"
Renal)Cell)Carcinoma)Signaling) 0.984" 0.0682" FOS,"FGFR1,"RAC1,"FGFR2,"CRK,"IRS2"
VEGF)Signaling) 0.977" 0.0642" PTK2,"FGFR1,"FGFR2,"IRS2,"ACTN4,"ELAVL1,"
ACTN1"
1,)253dihydroxyvitamin)D3)Biosynthesis) 0.975" 0.333" POR"
Inosine35'3phosphate)Biosynthesis)II) 0.975" 0.333" ADSL"
Hypusine)Biosynthesis) 0.975" 0.333" DOHH"
Oxidized)GTP)and)dGTP)Detoxification) 0.975" 0.333" DDX6"
S3adenosyl3L3methionine)Biosynthesis) 0.975" 0.333" MAT2A"
Neuroinflammation)Signaling)Pathway) 0.962" 0.0514" TRAF3,"FGFR1,"CREB3L3,"FGFR2,"PLA2G3,"
NCSTN,"PSEN2,"FOS,"TICAM1,"APH1A,"TLR6,"
TGFB3,"ATF4,"IRS2,"PTGS2,"PPP3CA"
Cytotoxic)T)Lymphocyte3mediated)Apoptosis)of)Target)Cells) 0.955" 0.0938" FADD,"CASP6,"CASP7"
IL32)Signaling) 0.945" 0.0714" CSNK2A2,"FOS,"FGFR1,"FGFR2,"IRS2"
IL31)Signaling) 0.916" 0.0652" ECSIT,"FOS,"MAP2K7,"NFKBIA,"GNA15,"
ADCY3"
Docosahexaenoic)Acid)(DHA))Signaling) 0.913" 0.0769" FGFR1,"FGFR2,"IRS2,"PNPLA2"
ERK5)Signaling) 0.907" 0.0694" MYC,"FOS,"YWHAB,"CREB3L3,"ATF4"
!
! 214!
FLT3)Signaling)in)Hematopoietic)Progenitor)Cells) 0.9" 0.0645" STAT4,"FGFR1,"CREB3L3,"ATF4,"FGFR2,"
IRS2"
γ3linolenate)Biosynthesis)II)(Animals)) 0.896" 0.118" SLC27A2,"CYB5A"
Role)of)JAK2)in)Hormone3like)Cytokine)Signaling) 0.896" 0.0882" SOCS3,"PTPN1,"IRS2"
CD27)Signaling)in)Lymphocytes) 0.89" 0.0755" FOS,"MAP2K7,"NFKBIA,"MAP3K5"
Semaphorin)Signaling)in)Neurons) 0.89" 0.0755" PTK2,"CFL2,"RAC1,"LIMK1"
GPCR3Mediated)Integration)of)Enteroendocrine)Signaling)
Exemplified)by)an)L)Cell)
0.889" 0.0685" GNA15,"PDIA3,"ADCY3,"ITPR1,"ADRB2"
Neuropathic)Pain)Signaling)In)Dorsal)Horn)Neurons) 0.888" 0.0609" FOS,"PRKCI,"PDIA3,"FGFR1,"FGFR2,"IRS2,"
ITPR1"
VEGF)Family)Ligand3Receptor)Interactions) 0.884" 0.0638" FOS,"PRKCI,"FGFR1,"PLA2G3,"FGFR2,"IRS2"
IL34)Signaling) 0.868" 0.0632" IL13RA1,"INPP5F,"FGFR1,"FGFR2,"IRS2,"
HMGA1"
MIF3mediated)Glucocorticoid)Regulation) 0.868" 0.0857" NFKBIA,"PLA2G3,"PTGS2"
PRPP)Biosynthesis)I) 0.858" 0.25" PRPS1"
Branched3chain)α3keto)acid)Dehydrogenase)Complex) 0.858" 0.25" DBT"
Valine)Degradation)I) 0.855" 0.111" AUH,"DBT"
ErbB23ErbB3)Signaling) 0.853" 0.0667" MYC,"NRG2,"FGFR1,"FGFR2,"IRS2"
Sumoylation)Pathway) 0.853" 0.0625" FOS,"NFKBIA,"CTBP2,"RANGAP1,"ARHGDIA,"
MAP3K5"
Salvage)Pathways)of)Pyrimidine)Ribonucleotides) 0.838" 0.0619" DAPK1,"UPP1,"CMPK1,"PCK1,"CDA,"LIMK1"
!
! 215!
Glioma)Invasiveness)Signaling) 0.836" 0.0658" PTK2,"TIMP4,"FGFR1,"FGFR2,"IRS2"
Toll3like)Receptor)Signaling) 0.836" 0.0658" ECSIT,"FOS,"NFKBIA,"TICAM1,"TLR6"
Gα12/13)Signaling) 0.834" 0.0567" PTK2,"MAP2K7,"NFKBIA,"F2RL1,"FGFR1,"
FGFR2,"IRS2,"MAP3K5"
Hepatic)Fibrosis)/)Hepatic)Stellate)Cell)Activation) 0.825" 0.0535" CTGF,"NGFR,"FGFR1,"KLF6,"SMAD7,"TGFB3,"
BAMBI,"FGFR2,"SERPINE1,"IFNAR1"
Thrombin)Signaling) 0.825" 0.0524" PTK2,"ARHGEF4,"PRKCI,"GNA15,"PDIA3,"
ARHGEF16,"FGFR1,"ADCY3,"FGFR2,"IRS2,"
ITPR1"
Glioma)Signaling) 0.82" 0.0583" CDKN2D,"PRKCI,"PA2G4,"FGFR1,"CDKN1A,"
FGFR2,"IRS2"
DNA)damage3induced)143333σ)Signaling) 0.817" 0.105" CCNE1,"RAD9A"
PKCθ)Signaling)in)T)Lymphocytes) 0.816" 0.0545" FOS,"NFKBIA,"BCL10,"FGFR1,"RAC1,"FGFR2,"
IRS2,"MAP3K5,"PPP3CA"
Ceramide)Signaling) 0.808" 0.0606" FOS,"NGFR,"FGFR1,"FGFR2,"IRS2,"SMPD2"
Role)of)CHK)Proteins)in)Cell)Cycle)Checkpoint)Control) 0.808" 0.0702" RAD9A,"CDKN1A,"CHEK2,"CDC25A"
Role)of)MAPK)Signaling)in)the)Pathogenesis)of)Influenza) 0.803" 0.0641" PAFAH1B2,"MAP2K7,"PLA2G3,"PTGS2,"
MAP3K5"
IL317A)Signaling)in)Airway)Cells) 0.803" 0.0641" NFKBIA,"FGFR1,"IL17RC,"FGFR2,"IRS2"
Glioblastoma)Multiforme)Signaling) 0.784" 0.0536" MYC,"CCNE1,"PDIA3,"FGFR1,"CDKN1A,"
RAC1,"FGFR2,"IRS2,"ITPR1"
!
! 216!
iCOS3iCOSL)Signaling)in)T)Helper)Cells) 0.781" 0.0569" NFKBIA,"FGFR1,"RAC1,"FGFR2,"IRS2,"ITPR1,"
PPP3CA"
23ketoglutarate)Dehydrogenase)Complex) 0.769" 0.2" DLST"
Tetrapyrrole)Biosynthesis)II) 0.769" 0.2" HMBS"
Myo3inositol)Biosynthesis) 0.769" 0.2" INPP5F"
Axonal)Guidance)Signaling) 0.768" 0.046" TUBA1B,"RGS3,"PDIA3,"CXCR4,"FGFR1,"
CRKL,"RAC1,"FGFR2,"CRK,"KEL,"LIMK1,"
PTK2,"SEMA6D,"PRKCI,"SDCBP,"GNA15,"
CFL2,"NGFR,"IRS2,"LNPEP,"PPP3CA"
Cardiac)Hypertrophy)Signaling) 0.756" 0.0498" MAP2K7,"GNA15,"PDIA3,"FGFR1,"ADCY3,"
TGFB3,"FGFR2,"IRS2,"MAP3K5,"MAPKAPK2,"
PPP3CA,"ADRB2"
Dendritic)Cell)Maturation) 0.755" 0.0515" STAT4,"NFKBIA,"PDIA3,"NGFR,"FGFR1,"
CREB3L3,"ATF4,"FGFR2,"IRS2,"IFNAR1"
Production)of)Nitric)Oxide)and)Reactive)Oxygen)Species)in)
Macrophages)
0.755" 0.0515" FOS,"MAP2K7,"NFKBIA,"PRKCI,"NGFR,"
FGFR1,"RAC1,"FGFR2,"IRS2,"MAP3K5"
CREB)Signaling)in)Neurons) 0.75" 0.0505" PRKCI,"POLR2A,"GNA15,"PDIA3,"FGFR1,"
CREB3L3,"ADCY3,"ATF4,"FGFR2,"IRS2,"ITPR1"
Synaptic)Long)Term)Potentiation) 0.745" 0.0556" PRKCI,"GNA15,"PDIA3,"CREB3L3,"ATF4,"
ITPR1,"PPP3CA"
!
! 217!
eNOS)Signaling) 0.743" 0.0523" HSP90B1,"PRKCI,"FGFR1,"ADCY3,"HSPA9,"
SLC7A1,"FGFR2,"IRS2,"ITPR1"
Melanoma)Signaling) 0.734" 0.0656" FGFR1,"CDKN1A,"FGFR2,"IRS2"
Phospholipase)C)Signaling) 0.73" 0.0492" ARHGEF4,"PRKCI,"AHNAK,"HDAC8,"
ARHGEF16,"CREB3L3,"ADCY3,"RAC1,"
PLA2G3,"ATF4,"ITPR1,"PPP3CA"
Sirtuin)Signaling)Pathway) 0.73" 0.0479" PPARG,"TUBA1B,"GADD45B,"EPAS1,"TIMM44,"
GADD45G,"SMARCA5,"PCK1,"TOMM70,"MYC,"
GADD45A,"ATG4D,"RARB,"NAMPT"
Role)of)PKR)in)Interferon)Induction)and)Antiviral)Response) 0.723" 0.0732" FADD,"TRAF3,"NFKBIA"
Estrogen)Biosynthesis) 0.723" 0.0732" POR,"CYP2U1,"HSD17B12"
Polyamine)Regulation)in)Colon)Cancer) 0.717" 0.0909" PPARG,"MYC"
Fatty)Acid)α3oxidation) 0.717" 0.0909" ALDH3B1,"PTGS2"
Acute)Phase)Response)Signaling) 0.704" 0.0511" ECSIT,"SOCS3,"FOS,"MAP2K7,"NFKBIA,"
NGFR,"CEBPB,"MAP3K5,"SERPINE1"
Wnt/Ca+)pathway) 0.701" 0.0635" PDIA3,"CREB3L3,"ATF4,"PPP3CA"
Activation)of)IRF)by)Cytosolic)Pattern)Recognition)Receptors) 0.701" 0.0635" FADD,"TRAF3,"NFKBIA,"IFNAR1"
Chondroitin)and)Dermatan)Biosynthesis) 0.698" 0.167" CSGALNACT1"
Glycine)Cleavage)Complex) 0.698" 0.167" AMT"
NAD)Biosynthesis)III) 0.698" 0.167" NAMPT"
GDP3mannose)Biosynthesis) 0.698" 0.167" GMPPB"
!
! 218!
Gap)Junction)Signaling) 0.691" 0.0498" TUBA1B,"GJB6,"PRKCI,"PDIA3,"FGFR1,"
ADCY3,"FGFR2,"IRS2,"ITPR1,"PPP3CA"
Role)of)NFAT)in)Cardiac)Hypertrophy) 0.69" 0.0489" MAP2K7,"PRKCI,"HDAC8,"PDIA3,"FGFR1,"
ADCY3,"TGFB3,"FGFR2,"IRS2,"ITPR1,"
PPP3CA"
Pyrimidine)Deoxyribonucleotides)De)Novo)Biosynthesis)I) 0.687" 0.087" CMPK1,"PCK1"
IL38)Signaling) 0.674" 0.0493" PTK2,"FOS,"PRKCI,"FGFR1,"RAC1,"HBEGF,"
FGFR2,"IRS2,"PTGS2,"LIMK1"
Nicotine)Degradation)II) 0.668" 0.0615" POR,"CYP2U1,"CSGALNACT1,"FMO5"
Role)of)RIG13like)Receptors)in)Antiviral)Innate)Immunity) 0.662" 0.0682" FADD,"TRAF3,"NFKBIA"
Stearate)Biosynthesis)I)(Animals)) 0.662" 0.0682" ACOT2,"SLC27A2,"DBT"
IL322)Signaling) 0.66" 0.0833" SOCS3,"IL10RB"
Type)I)Diabetes)Mellitus)Signaling) 0.654" 0.0541" FADD,"SOCS3,"MAP2K7,"NFKBIA,"NGFR,"
MAP3K5"
Calcium3induced)T)Lymphocyte)Apoptosis) 0.653" 0.0606" PRKCI,"ITPR1,"ATP2A2,"PPP3CA"
Relaxin)Signaling) 0.651" 0.0506" FOS,"NFKBIA,"GNA15,"FGFR1,"ADCY3,"
PDE5A,"FGFR2,"IRS2"
Calcium)Signaling) 0.648" 0.0485" LETM1,"HDAC8,"ATP2B3,"CREB3L3,"ATF4,"
TPM1,"ITPR1,"ATP2A2,"PPP3CA,"Tpm3"
iNOS)Signaling) 0.643" 0.0667" FOS,"NFKBIA,"HMGA1"
Pyrimidine)Ribonucleotides)Interconversion) 0.643" 0.0667" SMARCAL1,"CMPK1,"PCK1"
!
! 219!
Mouse)Embryonic)Stem)Cell)Pluripotency) 0.642" 0.0536" MYC,"ID1,"ID2,"FGFR1,"FGFR2,"IRS2"
Ceramide)Biosynthesis) 0.638" 0.143" SPTLC2"
Thioredoxin)Pathway) 0.638" 0.143" TXNRD3"
Pentose)Phosphate)Pathway)(Non3oxidative)Branch)) 0.638" 0.143" RPE"
Phosphatidylcholine)Biosynthesis)I) 0.638" 0.143" PCYT1A"
Acetyl3CoA)Biosynthesis)I)(Pyruvate)Dehydrogenase)Complex)) 0.638" 0.143" DBT"
IL317A)Signaling)in)Gastric)Cells) 0.633" 0.08" FOS,"IL17RC"
Bupropion)Degradation) 0.633" 0.08" POR,"CYP2U1"
G3Protein)Coupled)Receptor)Signaling) 0.627" 0.0461" GPR17,"NFKBIA,"GNA15,"DUSP1,"FGFR1,"
CREB3L3,"ADCY3,"ADORA3,"ATF4,"PDE5A,"
FGFR2,"IRS2,"ADRB2"
Role)of)IL317F)in)Allergic)Inflammatory)Airway)Diseases) 0.625" 0.0652" CREB3L3,"IL17RC,"ATF4"
Triacylglycerol)Biosynthesis) 0.625" 0.0652" MBOAT2,"DBT,"DGAT1"
Gαq)Signaling) 0.622" 0.0497" NFKBIA,"PRKCI,"GNA15,"FGFR1,"FGFR2,"
IRS2,"ITPR1,"PPP3CA"
p70S6K)Signaling) 0.615" 0.0507" PRKCI,"F2RL1,"YWHAB,"PDIA3,"FGFR1,"
FGFR2,"IRS2"
IL310)Signaling) 0.609" 0.058" SOCS3,"FOS,"NFKBIA,"IL10RB"
Remodeling)of)Epithelial)Adherens)Junctions) 0.609" 0.058" TUBA1B,"ARF6,"ACTN4,"ACTN1"
nNOS)Signaling)in)Neurons) 0.607" 0.0638" CAPN5,"PRKCI,"PPP3CA"
Pyrimidine)Ribonucleotides)De)Novo)Biosynthesis) 0.607" 0.0638" SMARCAL1,"CMPK1,"PCK1"
!
! 220!
Corticotropin)Releasing)Hormone)Signaling) 0.605" 0.0504" FOS,"PRKCI,"CREB3L3,"ADCY3,"ATF4,"ITPR1,"
PTGS2"
Dopamine3DARPP32)Feedback)in)cAMP)Signaling) 0.595" 0.0488" PRKCI,"PDIA3,"CREB3L3,"ADCY3,"ATF4,"
ITPR1,"ATP2A2,"PPP3CA"
Endometrial)Cancer)Signaling) 0.595" 0.0571" MYC,"FGFR1,"FGFR2,"IRS2"
NF3κB)Activation)by)Viruses) 0.594" 0.0538" NFKBIA,"PRKCI,"FGFR1,"FGFR2,"IRS2"
Histidine)Degradation)III) 0.588" 0.125" HAL"
Sphingomyelin)Metabolism) 0.588" 0.125" SMPD2"
UVC3Induced)MAPK)Signaling) 0.574" 0.0612" FOS,"PRKCI,"SMPD2"
IL315)Production) 0.563" 0.0714" PTK2,"PRKCI"
Sphingosine)and)Sphingosine313phosphate)Metabolism) 0.545" 0.111" SGPP1"
Prostanoid)Biosynthesis) 0.545" 0.111" PTGS2"
Sucrose)Degradation)V)(Mammalian)) 0.545" 0.111" KHK"
Leucine)Degradation)I) 0.545" 0.111" AUH"
Heme)Biosynthesis)II) 0.545" 0.111" HMBS"
Acute)Myeloid)Leukemia)Signaling) 0.527" 0.0505" MYC,"MAP2K7,"FGFR1,"FGFR2,"IRS2"
TNFR2)Signaling) 0.521" 0.0667" FOS,"NFKBIA"
Acetone)Degradation)I)(to)Methylglyoxal)) 0.521" 0.0667" POR,"CYP2U1"
RhoA)Signaling) 0.519" 0.0484" PTK2,"CFL2,"CDC42EP5,"EZR,"CDC42EP2,"
LIMK1"
Ketogenesis) 0.507" 0.1" BDH1"
!
! 221!
Ketolysis) 0.507" 0.1" BDH1"
Role)of)JAK1)and)JAK3)in)γc)Cytokine)Signaling) 0.506" 0.0519" SOCS3,"FGFR1,"FGFR2,"IRS2"
Chemokine)Signaling) 0.506" 0.0519" PTK2,"FOS,"CXCR4,"LIMK1"
Sperm)Motility) 0.492" 0.0472" PTK2,"PAFAH1B2,"PRKCI,"PDIA3,"PLA2G3,"
ITPR1"
RhoGDI)Signaling) 0.491" 0.0452" ARHGEF4,"GNA15,"CFL2,"EZR,"ARHGEF16,"
RAC1,"ARHGDIA,"LIMK1"
Colorectal)Cancer)Metastasis)Signaling) 0.484" 0.0433" MYC,"FOS,"GRK3,"FGFR1,"TLR6,"ADCY3,"
RAC1,"TGFB3,"FGFR2,"IRS2,"PTGS2"
Natural)Killer)Cell)Signaling) 0.484" 0.0469" PRKCI,"INPP5F,"FGFR1,"RAC1,"FGFR2,"IRS2"
GM3CSF)Signaling) 0.484" 0.0506" FGFR1,"FGFR2,"IRS2,"PPP3CA"
431BB)Signaling)in)T)Lymphocytes) 0.484" 0.0625" NFKBIA,"MAP3K5"
Fatty)Acid)β3oxidation)I) 0.484" 0.0625" SLC27A2,"AUH"
Pentose)Phosphate)Pathway) 0.473" 0.0909" RPE"
Purine)Nucleotides)De)Novo)Biosynthesis)II) 0.473" 0.0909" ADSL"
Dolichyl3diphosphooligosaccharide)Biosynthesis) 0.473" 0.0909" ALG5"
Nicotine)Degradation)III) 0.472" 0.0536" POR,"CYP2U1,"CSGALNACT1"
Antiproliferative)Role)of)Somatostatin)Receptor)2) 0.462" 0.0494" FGFR1,"CDKN1A,"FGFR2,"IRS2"
Phagosome)Formation) 0.459" 0.0458" PRKCI,"PDIA3,"FGFR1,"TLR6,"FGFR2,"IRS2"
mTOR)Signaling) 0.459" 0.0435" EIF3F,"RHEB,"PRKCI,"FGFR1,"RAC1,"FGFR2,"
IRS2,"EIF4G1,"RPS11"
!
! 222!
Chondroitin)Sulfate)Biosynthesis) 0.459" 0.0526" B4GALT7,"XYLT2,"CSGALNACT1"
IL315)Signaling) 0.452" 0.0488" PTK2,"FGFR1,"FGFR2,"IRS2"
Cholecystokinin/Gastrin3mediated)Signaling) 0.45" 0.0467" PTK2,"FOS,"PRKCI,"ITPR1,"PTGS2"
DNA)Methylation)and)Transcriptional)Repression)Signaling) 0.449" 0.0588" CHD3,"MBD2"
Acyl3CoA)Hydrolysis) 0.442" 0.0833" ACOT2"
Antioxidant)Action)of)Vitamin)C) 0.441" 0.0463" PAFAH1B2,"NFKBIA,"PDIA3,"PLA2G3,"
TXNRD3"
Dermatan)Sulfate)Biosynthesis) 0.435" 0.0508" B4GALT7,"XYLT2,"CSGALNACT1"
PPARα/RXRα)Activation) 0.429" 0.043" HSP90B1,"MAP2K7,"NFKBIA,"GNA15,"PDIA3,"
ADCY3,"TGFB3,"NCOA3"
Role)of)IL317A)in)Psoriasis) 0.415" 0.0769" IL17RC"
Fatty)Acid)Activation) 0.415" 0.0769" SLC27A2"
Choline)Biosynthesis)III) 0.415" 0.0769" PCYT1A"
Oleate)Biosynthesis)II)(Animals)) 0.415" 0.0769" CYB5A"
NAD)Phosphorylation)and)Dephosphorylation) 0.415" 0.0769" NADK"
Bile)Acid)Biosynthesis,) ) Neutral)Pathway) 0.415" 0.0769" CYP27A1"
Regulation)of)eIF4)and)p70S6K)Signaling) 0.41" 0.0429" EIF3F,"EIF4EBP2,"FGFR1,"FGFR2,"IRS2,"
EIF4G1,"RPS11"
GPCR3Mediated)Nutrient)Sensing)in)Enteroendocrine)Cells) 0.407" 0.0446" PRKCI,"GNA15,"PDIA3,"ADCY3,"ITPR1"
Cell)Cycle)Regulation)by)BTG)Family)Proteins) 0.403" 0.0541" CCNE1,"BTG2"
Phospholipases) 0.401" 0.0484" PAFAH1B2,"PDIA3,"PLA2G3"
!
! 223!
Xenobiotic)Metabolism)Signaling) 0.397" 0.0405" CUL3,"SRA1,"HSP90B1,"MAP2K7,"PRKCI,"
FGFR1,"FGFR2,"ALDH3B1,"IRS2,"MAP3K5,"
FMO5,"ESD"
Role)of)NFAT)in)Regulation)of)the)Immune)Response) 0.391" 0.0417" FOS,"NFKBIA,"GNA15,"FGFR1,"FGFR2,"IRS2,"
ITPR1,"PPP3CA"
Isoleucine)Degradation)I) 0.39" 0.0714" AUH"
Androgen)Biosynthesis) 0.39" 0.0714" SRD5A2"
Phenylalanine)Degradation)IV)(Mammalian,) ) via)Side)Chain)) 0.39" 0.0714" SLC27A2"
Colanic)Acid)Building)Blocks)Biosynthesis) 0.39" 0.0714" GMPPB"
Antigen)Presentation)Pathway) 0.389" 0.0526" PDIA3,"CANX"
Cdc42)Signaling) 0.384" 0.0419" FOS,"PRKCI,"CFL2,"CDC42EP5,"TNK2,"
CDC42EP2,"LIMK1"
Melatonin)Degradation)I) 0.369" 0.0462" POR,"CYP2U1,"CSGALNACT1"
Histidine)Degradation)VI) 0.368" 0.0667" HAL"
Mitochondrial)Dysfunction) 0.36" 0.0409" GSR,"APH1A,"TXN2,"LRRK2,"NCSTN,"PSEN2,"
CYB5A"
TGF3β)Signaling) 0.352" 0.043" FOS,"SMAD7,"TGFB3,"SERPINE1"
α3Adrenergic)Signaling) 0.352" 0.043" PRKCI,"PHKB,"ADCY3,"ITPR1"
Eicosanoid)Signaling) 0.35" 0.0448" PAFAH1B2,"PLA2G3,"PTGS2"
Vitamin3C)Transport) 0.347" 0.0625" TXNRD3"
Bladder)Cancer)Signaling) 0.344" 0.0426" MYC,"DAPK1,"PA2G4,"CDKN1A"
!
! 224!
cAMP3mediated)signaling) 0.34" 0.0395" GPR17,"DUSP1,"CREB3L3,"ADCY3,"PDE5A,"
ADORA3,"ATF4,"PPP3CA,"ADRB2"
Retinol)Biosynthesis) 0.339" 0.0476" PNPLA2,"ESD"
Phagosome)Maturation) 0.338" 0.0405" M6PR,"TUBA1B,"ATP6V0A2,"CANX,"BET1L,"
NAPA"
Mitochondrial)L3carnitine)Shuttle)Pathway) 0.328" 0.0588" SLC27A2"
CNTF)Signaling) 0.323" 0.0429" FGFR1,"FGFR2,"IRS2"
Superpathway)of)Melatonin)Degradation) 0.323" 0.0429" POR,"CYP2U1,"CSGALNACT1"
Systemic)Lupus)Erythematosus)Signaling) 0.316" 0.0386" FOS,"LSM12,"PRPF3,"FGFR1,"SNRNP70,"
PRPF39,"SF3B4,"FGFR2,"IRS2"
Role)of)Osteoblasts,) ) Osteoclasts)and)Chondrocytes)in)
Rheumatoid)Arthritis)
0.316" 0.0386" FOS,"MAP2K7,"NFKBIA,"NGFR,"FGFR1,"
FGFR2,"IRS2,"MAP3K5,"PPP3CA"
D3myo3inositol)(1,)4,)5)3trisphosphate)Degradation) 0.31" 0.0556" INPP5F"
MSP3RON)Signaling)Pathway) 0.306" 0.0417" FGFR1,"FGFR2,"IRS2"
Melatonin)Signaling) 0.306" 0.0417" MAP2K7,"PRKCI,"PDIA3"
Granulocyte)Adhesion)and)Diapedesis) 0.305" 0.0387" CLDN1,"CXCR4,"EZR,"NGFR,"CLDN6,"CLDN3,"
CCL19"
T)Helper)Cell)Differentiation) 0.298" 0.0411" STAT4,"NGFR,"IL10RB"
Thyroid)Cancer)Signaling) 0.296" 0.0435" PPARG,"MYC"
1D3myo3inositol)Hexakisphosphate)Biosynthesis)II)(Mammalian)) 0.294" 0.0526" INPP5F"
D3myo3inositol)(1,)3,)4)3trisphosphate)Biosynthesis) 0.294" 0.0526" INPP5F"
!
! 225!
Histamine)Degradation) 0.294" 0.0526" ALDH3B1"
Agrin)Interactions)at)Neuromuscular)Junction) 0.283" 0.04" PTK2,"NRG2,"RAC1"
Hepatic)Cholestasis) 0.272" 0.0375" NFKBIA,"PRKCI,"CYP27A1,"NGFR,"ADCY3,"
TGFB3"
CDK5)Signaling) 0.268" 0.0381" FOSB,"EGR1,"NGFR,"ADCY3"
Oxidative)Ethanol)Degradation)III) 0.265" 0.0476" ALDH3B1"
Assembly)of)RNA)Polymerase)II)Complex) 0.259" 0.04" POLR2A,"DR1"
Methionine)Degradation)I)(to)Homocysteine)) 0.252" 0.0455" MAT2A"
Role)of)Lipids/Lipid)Rafts)in)the)Pathogenesis)of)Influenza) 0.239" 0.0435" IFNAR1"
Putrescine)Degradation)III) 0.239" 0.0435" ALDH3B1"
Role)of)JAK1,) ) JAK2)and)TYK2)in)Interferon)Signaling) 0.228" 0.0417" IFNAR1"
Glutathione)Redox)Reactions)I) 0.228" 0.0417" GSR"
CDP3diacylglycerol)Biosynthesis)I) 0.228" 0.0417" MBOAT2"
Superpathway)of)D3myo3inositol)(1,)4,)5)3trisphosphate)Metabolism) 0.228" 0.0417" INPP5F"
TCA)Cycle)II)(Eukaryotic)) 0.228" 0.0417" DLST"
Cysteine)Biosynthesis)III)(mammalia)) 0.228" 0.0417" MAT2A"
Triacylglycerol)Degradation) 0.227" 0.037" ABHD6,"PNPLA2"
Role)of)JAK)family)kinases)in)IL363type)Cytokine)Signaling) 0.217" 0.04" SOCS3"
Tryptophan)Degradation)X)(Mammalian,) ) via)Tryptamine)) 0.217" 0.04" ALDH3B1"
Ethanol)Degradation)IV) 0.217" 0.04" ALDH3B1"
Phosphatidylglycerol)Biosynthesis)II)(Non3plastidic)) 0.207" 0.0385" MBOAT2"
!
! 226!
Synaptic)Long)Term)Depression) 0" 0.0333" PAFAH1B2,"PRKCI,"GNA15,"PDIA3,"PLA2G3,"
ITPR1"
LPS/IL31)Mediated)Inhibition)of)RXR)Function) 0" 0.027" ECSIT,"MAP2K7,"SLC27A2,"NGFR,"ALDH3B1,"
FMO5"
TREM1)Signaling) 0" 0.0267" NLRC3,"TLR6"
FcγRIIB)Signaling)in)B)Lymphocytes) 0" 0.0353" FGFR1,"FGFR2,"IRS2"
CCR5)Signaling)in)Macrophages) 0" 0.0211" FOS,"PRKCI"
HIF1α)Signaling) 0" 0.0323" EGLN2,"FGFR1,"FGFR2,"IRS2"
Human)Embryonic)Stem)Cell)Pluripotency) 0" 0.035" FGFR1,"SMAD7,"TGFB3,"FGFR2,"IRS2"
Androgen)Signaling) 0" 0.0219" PRKCI,"POLR2A,"GNA15"
Role)of)NANOG)in)Mammalian)Embryonic)Stem)Cell)Pluripotency) 0" 0.0234" FGFR1,"FGFR2,"IRS2"
Communication)between)Innate)and)Adaptive)Immune)Cells) 0" 0.0105" TLR6"
Ovarian)Cancer)Signaling) 0" 0.0333" PA2G4,"FGFR1,"FGFR2,"IRS2,"PTGS2"
Altered)T)Cell)and)B)Cell)Signaling)in)Rheumatoid)Arthritis) 0" 0.0222" TRAF3,"TLR6"
Atherosclerosis)Signaling) 0" 0.0236" PAFAH1B2,"CXCR4,"PLA2G3"
Gαs)Signaling) 0" 0.0364" CREB3L3,"ADCY3,"ATF4,"ADRB2"
Inhibition)of)Matrix)Metalloproteases) 0" 0.0256" TIMP4"
Agranulocyte)Adhesion)and)Diapedesis) 0" 0.0311" CLDN1,"CXCR4,"EZR,"CLDN6,"CLDN3,"CCL19"
Nucleotide)Excision)Repair)Pathway) 0" 0.0286" POLR2A"
Iron)homeostasis)signaling)pathway) 0" 0.0365" EPAS1,"ATP6V0A2,"CREB3L3,"GDF15,"HSPA9"
Coagulation)System) 0" 0.0286" SERPINE1"
!
! 227!
LXR/RXR)Activation) 0" 0.0165" NGFR,"PTGS2"
FXR/RXR)Activation) 0" 0.0159" PPARG,"CYP27A1"
Regulation)of)Actin3based)Motility)by)Rho) 0" 0.0333" RAC1,"ARHGDIA,"LIMK1"
Caveolar3mediated)Endocytosis)Signaling) 0" 0.0282" PTPN1,"COPB1"
Oncostatin)M)Signaling) 0" 0.025" EPAS1"
Mechanisms)of)Viral)Exit)from)Host)Cells) 0" 0.0244" PRKCI"
Cellular)Effects)of)Sildenafil)(Viagra)) 0" 0.0305" PDIA3,"ADCY3,"PDE5A,"ITPR1"
Factors)Promoting)Cardiogenesis)in)Vertebrates) 0" 0.0326" CCNE1,"PRKCI,"TGFB3"
G)Beta)Gamma)Signaling) 0" 0.025" PRKCI,"GNA15,"HBEGF"
Crosstalk)between)Dendritic)Cells)and)Natural)Killer)Cells) 0" 0.0225" TNFSF10,"NECTIN2"
Neuroprotective)Role)of)THOP1)in)Alzheimer's)Disease) 0" 0.0167" HTRA1,"PRSS27"
Role)of)Wnt/GSK33β)Signaling)in)the)Pathogenesis)of)Influenza) 0" 0.026" NCOA3,"IFNAR1"
Nur77)Signaling)in)T)Lymphocytes) 0" 0.0169" PPP3CA"
OX40)Signaling)Pathway) 0" 0.022" TRAF3,"NFKBIA"
Cell)Cycle)Control)of)Chromosomal)Replication) 0" 0.0357" CDK9,"CHEK2"
Actin)Nucleation)by)ARP3WASP)Complex) 0" 0.0161" RAC1"
Transcriptional)Regulatory)Network)in)Embryonic)Stem)Cells) 0" 0.0185" SMARCAD1"
Netrin)Signaling) 0" 0.0308" RAC1,"PPP3CA"
Heparan)Sulfate)Biosynthesis) 0" 0.0241" B4GALT7,"XYLT2"
Thyroid)Hormone)Metabolism)II)(via)Conjugation)and/or)
Degradation))
0" 0.0233" CSGALNACT1"
!
! 228!
Dopamine)Degradation) 0" 0.027" ALDH3B1"
tRNA)Splicing) 0" 0.0238" PDE5A"
Pyridoxal)5'3phosphate)Salvage)Pathway) 0" 0.0308" DAPK1,"LIMK1"
Serotonin)Degradation) 0" 0.026" ALDH3B1,"CSGALNACT1"
Chondroitin)Sulfate)Biosynthesis)(Late)Stages)) 0" 0.0204" CSGALNACT1"
Noradrenaline)and)Adrenaline)Degradation) 0" 0.025" ALDH3B1"
Ethanol)Degradation)II) 0" 0.027" ALDH3B1"
Superpathway)of)Methionine)Degradation) 0" 0.027" MAT2A"
Gαi)Signaling) 0" 0.0244" GPR17,"ADCY3,"ADORA3"
Oxidative)Phosphorylation) 0" 0.00917" CYB5A"
HIPPO)signaling) 0" 0.0115" YWHAB"
PCP)pathway) 0" 0.0164" RAC1"
Cardiac)β3adrenergic)Signaling) 0" 0.0284" GRK3,"ADCY3,"PDE5A,"ATP2A2"
Interferon)Signaling) 0" 0.0278" IFNAR1"
GABA)Receptor)Signaling) 0" 0.0211" AP2M1,"ADCY3"
Wnt/β3catenin)Signaling) 0" 0.0349" SOX4,"MYC,"CSNK2A2,"RARB,"TGFB3,"SOX3"
Serotonin)Receptor)Signaling) 0" 0.0233" ADCY3"
Phototransduction)Pathway) 0" 0.0189" PDC"
Dopamine)Receptor)Signaling) 0" 0.013" ADCY3"
BMP)signaling)pathway) 0" 0.0122" SMAD7"
Gustation)Pathway) 0" 0.026" ADCY3,"PDE5A,"P2RX5,"ITPR1"
!
! 229!
autophagy) 0" 0.0323" ATG4D,"NBR1"
Cancer)Drug)Resistance)By)Drug)Efflux) 0" 0.0182" PTGS2"
! !
!
! 230!
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Publications!!
1.!Ng,!H.!M*,!Ho,.J..C.*,!Nong,!W.,!Hui,!J.!H.!L.,!Lai,!K.!P.,!&!Wong!C.!K.!C.!(2020).!
GenomeIwide!analysis!of!MicroRNAImessenger!RNA!interactome!in!exIvivo!gill!
filaments,!Anguilla!japonica.!BMC!Genomics,!21,!208.!(*Same!Contribution)!
!
2.!Lai,!K.P.,!Lin,!X.,!Tam,!N.,!Ho,.J.C.H.,!Wong,!M.K.IS.,!Gu,!J.,!Chan,!T.F.!and!Tse,!
W.K.F.!(2020),!Osmotic!stress!induces!gut!microbiota!community!shift!in!fish.!
Environ!Microbiol.! !
!
3.!Lai,!K.!P.,!Cheung,!A.,!Ho,.C..H.,!Tam,!N.!Y.,!Li,!J.!W.,!Lin,!X.,!Chan,!T.!F.,!Lee,!N.!P.,!
&!Li,!R.!(2020).!Transcriptomic!analysis!reveals!the!oncogenic!role!of!S6K1!in!
hepatocellular!carcinoma.!Journal!of!Cancer,!11(9),!2645I2655.! !
!
4.!Kwong,!E.!M.*,!Ho,.J..C.*,!Lau,!M.!C.,!You,!M.,!Jiang,!Y.,!&!Tse,!W.!K.!(2018).!
Restoration!of!polr1c!in!Early!Embryogenesis!Rescues!the!Type!3!Treacher!Collins!
Syndrome!Facial!Malformation!Phenotype!in!Zebrafish.!The!American!Journal!of!
Pathology,!188(2),!336I342.!(*Same!Contribution)!
!
5.!Fong,!H.!C.,!Ho,.J..C.,!Cheung,!A.!H.,!Lai,!K.,!&!Tse,!W.!K.!(2016).!Developmental!
toxicity!of!the!common!UV!filter,!benophenoneI2,!in!zebrafish!embryos.!
Chemosphere,!164,!413I420.!
!
6.!Tse,!W.!K.,!Li,!J.!W.,!Tse,!A.!C.,!Chan,!T.!F.,!Ho,.J..C.,!Wu,!R.!S.,!Wong,!C.K.!&!Lai,!K.!
P.!(2016).!Fatty!liver!disease!induced!by!perfluorooctane!sulfonate:!Novel!insight!
from!transcriptome!analysis.!Chemosphere,!159,!166I177.!
!
7.!Lau,!M.!C.,!Kwong,!E.!M.,!Lai,!K.!P.,!Li,!J.,!Ho,.J..C.,!Chan,!T.F.,!Wong,!C.!K.,!Jiang,!
Y.!J.,!&!Tse,!W.!K.!(2016).!Pathogenesis!of!POLR1CIdependent!Type!3!Treacher!
Collins!Syndrome!revealed!by!a!zebrafish!model.!Biochimica!Et!Biophysica!Acta!
(BBA)!I!Molecular!Basis!of!Disease,!1862(6),!1147I1158.!
!
8.!Ho,.J..C.,!Hsiao,!C.,!Kawakami,!K.,!&!Tse,!W.!K.!(2016).!Triclosan!(TCS)!exposure!
impairs!lipid!metabolism!in!zebrafish!embryos.!Aquatic!Toxicology,!173,!29I35.!
!
9.!Lai,!K.!P.,!Lin,!X.,!Tam,!N.,!Ho,.J.,!Wong,!M.!K.,!Gu,!J.,!Chan,!T.!F.,!&!Tse,!W.!
(2020).!Osmotic!stress!induces!gut!microbiota!community!shift!in!fish.!
Environmental!microbiology,!22(9),!3784–3802.!
!
! 248!
!
!
!
CURRICULUM,VITAE,!
Academic!qualification!of!the!thesis!author,!Mr!HO!Cheuk!Hin:!
! !
!! Received!the!degree!of!Bachelor!of!Science!(Honours)!from!Hong!Kong!
Baptist!University,!November!2016!
!
January! 2021!
!
!
! !
!
