2014_Wenger Seminars in Immunology Supplt1 Supplt3 Supplt4

Wenger, Buzgariu et al. 2014 Seminars in Immunology DOI: 10.1016/j.smim.2014.06.004

Injury-induced immune responses in Hydra

Yvan WENGER*, Wanda BUZGARIU*, Silke REITER and Brigitte GALLIOT°

* both authors equally contributed to this work

Department of Genetics and Evolution, Faculty of Sciences, University of Geneva 30 quai Ernest Ansermet, CH-1211 Geneva 04, Switzerland° Corresponding author: [email protected]; Tel: +41 22 379 67 74

Available online 30 July 2014DOI: 10.1016/j.smim.2014.06.004

SUPPLEMENTARY DATA

Supplement 1 to Table-1:

Methodology used for the identification of the 2’636 Hydra contigs encoding evolutionarily-conserved components of the innate immune system as deduced from Panther annotations of the Hydra vulgaris transcriptome p3

Supplement 2: Supplt2-DATASET panthertable_2636_Hydra immune genes.xlsxSee Excel file with the ENA accession number of all Hydra transcript Panther annotated as immune-related.ENA: European Nucleotide Archive

Supplement 3: Fasta file of Immune Genes that respond to injury in Hydra (see Figures 2, 3, 4, 5) p4

ADAPTOR proteins: Calreticulin, Ced6/GULP1, MYD88, SH3P1, TOLLIP, SWAP-70 4

Antimicrobial peptides (AMPs): Arminins 4

Antimicrobial peptides (AMPs): Hydramacins 6

Antimicrobial peptides (AMPs): Periculins 7

Antimicrobial proteins: LBP 7

B-cell Translocation Gene: BTG1 7

CHAPERONES: CRYABs (HSP20), DnaJB9 (HSP40), HSP16, HSP90 7

DODE proteins (Hydra species-restricted) 8

Fatty acid metabolism 8

GTPases Ras family (DiRas1; Rhes-like; Ras-ERGI) 8

KINASES: CAMK Ser/Thr protein kinases 9

KINASES: MAPK Ser/Thr protein kinases 9

KINASES: Tyrosine Kinase Non-receptor protein (TNK) 11

Leucine-rich Repeat Containing proteins (LRRC or LRC) 11

PHOSPHATASES: Tyrosine phosphatases 11

PROTEASES: Mannan-binding lectin serine protease (MASP, complement activation) 12

PROTEASES: Cystein-type endopeptidase (Caspases) 12

PROTEASES: Calcium-dependent cysteine-type endopeptidase 13

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http://www.sciencedirect.com/science/article/pii/S104453231400061X

http://www.ebi.ac.uk/ena/


mailto:[email protected]


PROTEASES: Matrix Metalloproteinases (MMPs) 13

PROTEASES: Membrane Metalloproteinases 14

PROTEASES: S1 peptidase 14

RECEPTORS: G-Protein Coupled Receptors (GPCR) 14

RECEPTORS: Tumor Necrosis Factor Receptor (TNFR) 16

RECEPTORS: Toll-Receptor Related (TRR) 16

RECEPTORS: Nod-like Receptors (NLR) 16

TNF Receptor Associated Factors (TRAFs): TRF-1, TRF-3, TRF-6 related 17

TRAFFICKING: ExoC 18

TRANSCRIPTION FACTORS (bZIP, AP1): AP1, Jun, ATFs, CREB, CREB like, Fos-related 18

TRANSCRIPTION FACTORS (bZIP, C/EBP): CCAAT-Binding Protein (C/EBP) 20

TRANSCRIPTION FACTORS (bZIP, CNC): NFE2F 20

TRANSCRIPTION FACTORS (REL-like domain): NF-AT5, NFkB 20

TRANSCRIPTION CO-REGULATORS or MODULATORS: ECD/SGT1, IkB, IRF2BP, LITAFs 21

Transposases: HARB like 21

Ubiquitination: Nedd8, Sequestosomes (SQSTM), SUGT1 14

Various proteins: ankyrin repeat 22

Supplement 4: Phylogenetic analysis of the Arminin gene families identified in Hydra p23

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Supplement 1 to Table-1

Supplement 1 to Table-1: Methodology used for the identification of the 2’636 Hydra contigs encoding evolutionarily-conserved components of the innate immune system as deduced from Panther annotations of the Hydra vulgaris transcriptome Sequences used in this study were RNA-seq transcriptomic sequences from Hydra vulgaris (strain Basel) produced by (Wenger and Galliot, 2013) available at the European Nucleotide Archive (ENA) under accessions HAAC01000001-HAAC01045250. A reduction of the sequence redundancy was done using CD-HIT-est and CD-HIT using a 95% sequence similarity thresholds on nucleotide sequences and on conceptually translated sequences, respectively (Li and Godzik, 2006). From this, 24'481 sequences were retrieved. Sequence annotation was carried out with PANTHER 9.0 using default threshold values (Mi et al. 2005). A list of panther families associated with immune functions was obtained by parsing the PANTHER9.0_HMM_classifications file (which contains gene ontology information about panther families) with the following keywords: B-cell, T-cell, immune, defense, NF-kappa, Toll, interferon, interleukin, interferon, complement (case insensitive). Each keyword was independently evaluated so that no false positives were reported. This yielded 4'279 panther families. 2’636 sequences corresponding to these families were retrieved from the Hydra dataset. On the tables shown above, the Panther affiliation number is indicated on the left of each category (PTHRxxxxx), the number of distinct Hydra transcripts for each family is indicated between brackets. For Hydra sequences accession numbers in each category, see Supplement 2.

References: Li W, Godzik A: Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences.

Bioinformatics 2006, 22(13):1658-1659.Mi H, Lazareva-Ulitsky B, Loo R, Kejariwal A, Vandergriff J, Rabkin S, Guo N, Muruganujan A, Doremieux O, Campbell

MJ et al: The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic acids research 2005, 33 (Database issue):D284-288.

Wenger Y, Galliot B: RNA-seq versus genome-predicted transcriptomes: a large population of novel transcripts identified in an Illumina-454 Hydra transcriptome. BMC Genomics 2013, 14:204.

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Supplement 3: Sequences of the immune genes tested for injury response in Hydra (see Wenger et al. Figures 2, 3 and 4)

ADAPTOR proteins: Calreticulin, Ced6/GULP1, MYD88, SH3P1, TOLLIP, SWAP-70>Ced6l_Hydvu ENA|HAAC01032305.1 TSA (PTHR11232:SF31, PTB DOMAIN-CONTAINING ENGULFMENT ADAPTER PROTEIN 1): Hydra vulgaris, contig miradenovo_c06482: 1869, 76, 1945 (+),T2M3D6 99% identical to PREDICTED: uncharacterized protein LOC100200374 [Hydra vulgaris] Sequence ID: ref|XP_002157703.1| Length: 630; 42% identical, 66% similar (10/14 -> 189/189) to Full= PTB domain-containing engulfment adapter protein 1; AltName: Full=Cell death protein 6 homolog; AltName: Full=PTB domain adapter protein CED-6 Sequence ID: sp|Q32PV0.1|GULP1_DANRE Cell death protein 6 homolog. May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. May play a role in the internalization and endosomal trafficking of various lrp1 ligandsMDKSNPQKRLQTIKKFQEGFVVFRAKYLGCIPVQKSKGVEVIKEAIRKLKIAHQLKKSEAGIKESKLMKVEIHISMNWIKIINSKSKVMVCNRPLHRVSYCADDNTDKKIFSFIAKDQESNTHSCFVLKCEKEATDLTLTFGEAFDLAYKRYIQTEKEELKKNKELINISAHIEEFKKENPKFQKGIEASTLLSSPRQMDEPLTRTVPLSASARLSSTLLEENLVKENTSENVITDNARFLSNIENSSYEVFQDASAHNHSSLNDFDWFNYSNSNNNAMHSRPFDHNVDPSIVDQLQDSKVSDSGLSNTDFFDFLSKSPSEQDFALTNDPFADNPHWNNVVKKELSISESFDNDVLNLPTNPFRVNSDQSCNNMYSQNGSARLESETKESDSFSQFLSSLVGRTENLEINNNSDQFSSGAFFNSFETNFDENGFKATNEINLSFETLNSNNLDLISPSEIQTSSTPRNDLSSIKCENSRPRPTGNTLKGNLLPAPPSKKTMKVTTAVSKPITPIAAPTVRSNSISTVRNNSIPTERNNSIPTERNNSIPADSESISNARDVKQSDASRKVNRLSVGNIAHILPNVEKAQSPNTDFRSRSRSSVSAKKQYSLFQVSKTLEGMID

>MyD88_Hydvu ENA|HAAC01031245.1 (PTHR15079, MYD88): DD_superfamily (N-Term), TIR-2 superfamily (C-term); deltablast: no CNIDARIAN blast at NCBI (?) although published (Miller et al. Genome Biol 2007), 1 st hit: myeloid differentiation primary response protein MyD88-A [Xenopus laevis] Sequence ID: ref|NP_001081001.1|Length: 283 Number of Matches: 1, 48% similar, 3e-44 ~ 200 reads, rather stable, low in the headCLVKLKRREVHSVFYMSMDCINKDQILNQSLLYPIMSQVSFLLNPICDGKDWRALAGVFDFTMEEVNVLSSACDPTMEFFKYYESKYGKKVTFTYVIESLQNIGRKDITLEIYKYTNDNNFIENKNQDLQYSVTQVNNFTLNNSYDVFISYAKDDISFAKLIKNRLENENGFKVCIDYCDFLPGYNPFEQICSVIEEKCRKVIVILSPNFNESNNCQTQAKIALSLSFEFNKNKVIPILYKKCVNTQVIFKNF*

>SH3P1_Hydvu ENA|HAAC01026770.1 TSA (PTHR22820:SF9, PROTEIN ENHANCER OF SEVENLESS 2B): Hydra vulgaris, contig meta-ga_rep_c08710: 1818, 3, 1821 (+) length 606 AAs; isoform of PREDICTED: uncharacterized protein LOC100211309 [Hydra vulgaris] Sequence ID: ref|XP_002162350.2|Length: 844; SH3 domain containing protein in the N-terminus; Protein with at least one Src homology 3 (SH3) domain. It is a small protein domain of about 50 amino-acid residues first identified as a conserved sequence in the non-catalytic part of several cytoplasmic protein tyrosine kinases (e.g. Src). Since then, it has been found in a great variety of other intracellular or membrane-associated proteins. The SH3 module might mediate the assembly of specific protein complexes by binding to proline-rich peptides.YLDSVIDSITSPDDEDSSNQLTGEADKYSEDFTKSDDSNENLDPPRSSHFITIFPFEPCEQNELKLEVGDLVDVLKTSETGWWKGRCLRTECDGWFPSSYVQPSYLSISNSFKNEIADDRGTVSDSEIQMIDAITLKRKYQVTNGYNSDNGDYSNKINELKNDCADPSNALKDRVLFKTEPPSKPVPPKPRKRHIQDKLINNPNIEERSQSCSDADKKDFEAFFKQSNIDHKDKKTIASKNDNGYLSPIDKLRPRSFQDTPQNNFFKLSNRFNNNMKPAWSLPSLNVGEQVKLSPDDDRPFLEPIPRKNKRYSVPNDSLYISQLSSDGNIALSTEVLHSEESKDSIEYESIVNENSFSTNVDLRDSSREDNNFLLKNDNTLKKIPPLSKNYLENDKPIVYEVLSQNISDQKIAGSSPSEDDNFIQRVYNKEIDSNRHSRLRTGHKRFSNLKSAIIEESECISPDEDTKKEFSVSLKNNEATLKNLNKLSTQTSSLNSDGKFLKEQDDQVGSSKLLSQGLKNSSSTQSLSSIASSTRSNPSTKLEQMNVRRAIANVVANSEHELTFSVGAILYELRPRNKEGLSYGILEDSNQGWYPSDAVEPYFIF

>TOLLIP_Hydvu ENA|HAAC01031352_1 (PTHR16461); 100% identical to PREDICTED: toll-interacting protein-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002167406.2|Length: 218 Number of Matches: 1; 100%; N-terminus (111 AAs) 98% identical to PREDICTED: toll-interacting protein-like [Hydra vulgaris] Sequence ID: ref|XP_004208657.1| Length: 128 Number of Matches: 1; 42% identical, 60% similar to toll-interacting protein [Homo sapiens] Sequence ID: ref|NP_061882.2| Length: 274 Number of Matches: 1; UNIPROT Q9H0E2 (TOLIP_HUMAN) Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity; Oligomerizes. Binds to TLR2 and the TLR4-MD2 complex via its C-terminus. Exists as complex with IRAK1 in unstimulated cells. Upon IL-1 signaling, binds to the activated IL-1 receptor complex containing IL-1RI, IL-1RacP and the adapter protein MyD88, where it interacts with the TIR domain of IL-1RacP. MyD88 then triggers IRAK1 autophosphorylation, which in turn leads to the dissociation of IRAK1 from Tollip and IL-1RAcP. Interacts with TOM1L2MASNDEEIIKNQRRQQVLTGELPDNFLKIESGQVFPASGQSLYYPASFGRYQEVGVLSMTVVQARLVKNYGYLTRMDPYCRVRIGLQTFETPTAYNGAKSPRWNKLIQCNLPENVREVYLEMFDECTFSVDERIAWCLIKIPDSVIMGEVLNEWFSLNGKQGEEKEGMIEIVFQYKKLPAGPMLVPSMVGPMVINPMVQPLIYPNAYGPQVIMQQPIQPVQPNFQQSSPGPQQIFESNPADLRTLKEMCPDMDVDIIKTVLQQCGGNIDKAAAQLLEMNAT

>SWAP70_Hydvu ENA|HAAC01028284.1 TSA (PTHR14383:SF5, FAMILY NOT NAMED): Hydra vulgaris, contig meta_rep_c16867: 1149, 3, 1152 (+); isoform with additional exon of >gi|449682972 |ref| XP_004210230.1| PREDICTED: switch-associated protein 70-like, partial [Hydra vulgaris]. The HAAC01028284 sequence is likely partial (missing the N-terminus 1-226) but contains a Pleckstrin Homology (PH) domain from positions 8 -106 (http://pfam.xfam.org/family/PF00169.24) and a Peptidase Gluzincin family (thermolysin-like proteinases, TLPs) domain detected on NCBI www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?RID=TSBJXDHJ014&mode=all from positions 206-303 but not by PFAM. Best vertebrate hit:

Q6A028 (SWP70_MOUSE): The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF), which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusionLKYYILEIIKSGFLVKKGHRIKSMKERWFVLTPDNLFYYDGKTKGAKKKGSICINKAVIIEPLFDMKSNRFRFLLNCGIKGVNYEIEALDLKSMNEWISAIQLCIDHSKDKTPLMRNLLERAQERKERRRKKAEEDQLRIENEALIQRQIQELQILKEAALAQSAVEAALLEEEKKRVEELELMKLEYEKLLEEERLARLSESEARANQQSILEEEMFKRQTLEKIKTEQENILNEERKIRESLEEMSKEQAIILEEERQRLKVLDAARQAAEDELKSAHLKLKEAEEERQLASLKVELAKEKTRKINLPVGLAKPLVVEQRGIVSHRGLGAFVEHDFSKKPLYLSSEQSPAAVNKINIDEGQRTEIVESNLLKPSESKEIFK

Antimicrobial peptides (AMPs): Arminins>ArmL1a_18976 ENA|HAAC01018976.1 TSA: Hydra vulgaris, contig isotig05299 GAAAGGCTATTAAAATCATTCTGTTTAATCATGGAGTTGTTTATAAAAATACAAAAACGTTTTCGGATGCGAAAACGTAGTTTTAATATTAAAAATCAAAGTATTTAATATTAAATACCGATAACAACATAACTTGATACAATTTTATATAAGCTGATATGATAAAAAGTTTTATCTTAGTTATTTCTATTACTTTTTAC

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http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?RID=TSBJXDHJ014&mode=all

http://pfam.xfam.org/family/PF00169.24

http://www.uniprot.org/uniprot/T2M3D6


CAGCCGCCGCAATAACAGCTGGTATATAAGGAACAAGTTTCCTCCATCGTATTCTTCGTACCCATCTCCATGGCTTTGCATCATTGATTTCTTACTTTTATCATTTAAATCGTCACTTTCTTCTTCAAGATCTTCAAGTATTTCTTTTTCAACTTTCATTTTTAATTTCTTCCTTCACATCCTCATAACTTCTTGCGTATGTCAACGCAATGAACGCCAAAAACAAAATTGCAAACACTGTCTTCATTTTAAAATCGATTTCATAAAAAAAGAAAAGTGACAACAGTTTTTATACCAGCCGATTGGAAAACATCACGTGTTTTATTTAAGGAAAGTAAACATTCTTGAGATTAGTTGTCTATGACATCTCATCTCT

>ArmL1b_44928 ENA|HAAC01044928.1 TSA: Hydra vulgaris, contig miradenovo_rep_c84590 CAACAAATGGTTATNTAAGGAGCAACTTTTCTCCATCGTACTCTTCGAATAGCTCTACGAAATCTCCATGGCTTTGCATCATTGAACTCTAAAAATTTTAACGATACTCTAACGTTACTATCTAATACGTCACTTTCCTCTTCAAGATCTTCAAATATTTCTCTTTCAACTTCATTTTTAATTTCTTCCTTCACATCCTCATAACTTTYTGCGTATGTGAACGCAATGAATGTCAAAAACAAAAATGCCAACACTGTCTTCATTTTTCAATTCTACTCCTTAA

>ArmL1c_30259 ENA|HAAC01030259.1 TSA: Hydra vulgaris, contig meta_rep_c29756 GTTATGTTCAGTAACTATTTCTAAATTTTTACACGAGTTATATTAAAGCTCATGTAAAAAAAAGATTTATTTTAGTTGTTTTCATTACTTTTTACCAACCGTCTTAACAACAAATGGCATGTAAGGAGCAACTTTTCTCCATCGCACTCTTCGAATAGCTCTACGAAATMTCCATGGCTTTGCATCATTGAACTCTCTAAAAATTTTAACGATACTCTAACGTTACTATCTAATACGTCACTTTCCTCTTCAAGATCATCAAATTTTTCG

>Arm1b1_02955 ENA|HAAC01002955.1 TSA: Hydra vulgaris, contig asmbl_2228 AAAAACACACGTGATGTTTTCCATCAGCTTGTATAAATACTGTTTCACTTTTATTTCTTAAGGAGTAGAATTGAAAAATGAAGACAGTGTTGGCATTTTTGTTTTTGACATTCATTGCTTTCACACACGCAGAAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAGTTGAAAGAGAAATATTTGAAGATCTTGAAGAGGAAAGTGACGTATTAGAAAGTAACGTTAGAGGTAATTTACTTTTTCTCTTTTTTATAATTTATCCACTGCAAGTTTTGGGTAAATTTAAAAAAAAAAAAGTATCGTTAAAATTTTTAGAGTTGAATGATGCAAAGCCATGGAGATTTCGTAGAGCTATTCGAAGAGTACGATGGAGAAAAGTTGCTCCTTACATACCATTTGTTGTTAGAACGGTTGGTAAAAAGTAATGGAAACAACTAAAATTAATCTTTTTGTAATATGAGCTTCAAAATAATTTGTTTGAAATCA

>Arm1b2_02961 ENA|HAAC01002961.1 TSA: Hydra vulgaris, contig asmbl_2229AAAAACACACGTGATGTTTTCCATCAGCTTGTATAAATACTGTTTCACTTTTATTTCTTAAGGAGTAGAATTGAAAAATGAAGACAGTGTTGGCATTTTTGTTTTTGACATTCATTGCTTTCACACACGCAGAAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAGTTGAAAGAGAAATATTTGAAGATCTTGAAGAGGAAAGTGACGTATTAGAAAGTAACGTTAGAGTATCGTTAAAATTTTTAGAGTTGAATGATGCAAAGCCATGGAGATTTCGTAGAGCTATTCGAAGAGTACGATGGAGAAAAGTTGCTCCTTACATACCATTTGTTGTTAGAACGGTTGGTAAAAAGTAATGGAAACAACTAAAATTAATCTTTTTGTAATATGAGCTTCAAAATAATTTGTTTGAAATCA

>Arm1bl1_44900 ENA|HAAC01044900.1 TSA: Hydra vulgaris, contig miradenovo_rep_c84485 GAGTAGAATTGAAAAATGAAGACAGTGTTGGCATTTTTGTTTTTGACATTCATTGCGTTCACATACGCAGAAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAGTTGAAAGAGAAATATTTGAAGATCTTGAAGAGGAAAGTGACGTATTAGATAGTAACGTTAGAGAGTTCAATGATGCAAAGCCATGGAGATTTCGTAGAGCTATTCGAAGAGTACGATGGAGAAAAGTTGCTCCTTACATACCATTTGTTGTTAGACGGTTGGTAAAAAGTAATGGAAACAACTAAATTAATCTTTTTGTAATATGAGCTTACAAAATAAATTGTTTAGAAAATTCTAAAATTTTTT

>Arm1bl2_44408 ENA|HAAC01044408.1 TSA: Hydra vulgaris, contig miradenovo_rep_c81715 AGGGAGTAGAATTGAAAATGAAGACAGTGTTGGCATTTTTGTTTTTGACATTCATTGCGTTCACATAACGACGGAAAGTTAATAGAAGGAATAGTAGAAAGGAAGAAATTAAAAATGAAGTTAGAAAGAGAAATATTTGAAGATCTTGAAGAGGAAAGTGACGTATTAGATAGTAACGTTAGAGAGTTCAATGATGCAAAGCCATGGAGATTTCGTAGAGCTATTCGAAGAGTAAGATGGAGAAAAGTTG

>Arm1bl3_30203 ENA|HAAC01030203.1 TSA: Hydra vulgaris, contig meta_rep_c29209 AGGGAGTAGAATTGAAAATGAAGACAGTGTTGGCATTTTTGTTTTTGACATTCATTGCGTTCACATAACGACGGAAAGTTAATAGAAGGAATAGTAGAAAGGAAGAAATTAAAAATGAAGTTAGAAAGAGAAATATTTGAAGATCTTGAAGAGGAAAGTGACGTATTAGATAGTAACGTTAGAGAGTTCAATGATGCAAAGCCATGGAGATTTCGTAGAGCTATTCGAAGAGTAAGATGGAGAAAAGTTGCTCCTTACATACCATTTGTTGTTAGAACGGTTGGTAAAAAGTAATGGAAGCACAGCAACCTCCATACGTATTTCGCCGACAGC

>Arm1c_30239 ENA|HAAC01030239.1 TSA: Hydra vulgaris, contig meta_rep_c29560 AAAAATGTATATTTACTGTTTTTAAAAAAAACACGCGATGTTTACCTTTGGCTAGTATAAATACTGTTCTACCTTTATTTCTTAAAAAGTTGATTTGGAAAATGAAGCCAGTTTTTGTCATTTTGTTTTTGACATGCATTGCGTTCACATATGCAGAAAGTTATGAGGATGTGAAAGAAGAAATTAAAAATGAAGTTGAAAGAGAAATATTTGAAGATCTTGAAGAGGAAAGTGACGTATTAGATAGTAACGTTAGAGAGTTCAATGATGCAAAGCCATGGAGATTTCGTAGAGCTATTCGAAGAGTGCGATGGAGAAAAGTTGCTCCTTACATGCCATTTGTTGTTAAGACGGTTGGTAAAAAGTAATGAAAACAACTAAAATAAATCTTTTTTTTACATGAGCTTTAATATAACTACGTGTAAAA

>Arm2a1_04602 ENA|HAAC01004602.1 TSA: Hydra vulgaris, contig asmbl_28873AAACACGTGATATTTTCCAATCGGCTGGTATAAAAACTGTTTCACTTTCTTTTTTTATAAAATCGATTTATAAAATGAAGACAGTGTTTGCAATTTTGTTTTTAGCATTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAAGAAGAAATTAAGAATGAAGTTGTAAAAGAAATACTTGAAGATCTTGAAGAAGAAAGTGACGAATTAGATGATAAAAGTAAAGGTAATTGACCTCTTCATCTTTATTTATATTGTATTTTA

>Arm2a2_44989 ENA|HAAC01044989.1 TSA: Hydra vulgaris, contig miradenovo_rep_c84858 GAAATCGATTTATAAAATGAAGACAGTGTTTGCAGTTTTGTTTTTGGCATTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAAGAAGAAATTAAAAATGAAGTTGAAAAAGAAATACTTGAAGATCTTGAAGAAGAAAGTGACGATTTAAATGATAAAAGTAAAGGTAATTGACTTCTTCATCTTTATTTATATTGTATTTTATTCCAACTGAGTTAATTTTTAAAAAATCTTTGACCTTTTTAGAAATCAATGATGCAAAGCCATGGAGATGGGTACGAAAAATACGATGGAGGAGACTTGTTCC

>Arm2a3_42736 ENA|HAAC01042736.1 TSA: Hydra vulgaris, contig miradenovo_rep_c70745 AAGTTCTCGCCATTACTAAAATTAAGACAATTTTSAAATCGATTTATAAAATGAAGACAGTGTTTGCAGTTTTGTTTTTGGCATTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAARGAAGAAATTAAAAATGAAGTTGAAAAAGAATACTTGAAGATCTTGAAGAAGAAAGTGACGATTTAAATGATAAAAGTAAGAATCAATGATGCAAAGCCATGGAGATGGGTACGAAAAATACGATGGAGAGACTTGTTCCTTACTACCAGCTGTAATTAAGGCGGCTGGTAAAAAGTAATAGAAACAACTAAGATAAAACTTTATGTCGTATCAGCTTATATAAAATTGTATCAAATTATTTTGGCATATTGTTATACGGTATTTAATAGT

>Arm2a4_44976 ENA|HAAC01044976.1 TSA: Hydra vulgaris, contig miradenovo_rep_c84800 GAAATCGATTTATAAAATGAAGACAGTGTTTGCAGTTTTGTTTTTGGCATTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAAGAAGAAATTAAAAATGAAGTTGAAAAAGAAATACTTGAAGATCTTGAAGAAGAAAGTGACGATTTAAATGATAAAAGTAAGAAATCAATGATGCAAAGCCATGGAGATGGGTACAAAAATACGATGGAGGAGACTTGTTCCTTATACCAGCTGTAATTAAGGCGGCTGGTAAAAAGTAATAGAAACAACTAAGATAAAACTTTATGTCGTATCAGCTTATATAAAATTGTATCAAATTATTTGGCATATTGTTATCGGTTA

>Arm2b1_30589 ENA|HAAC01030589.1 TSA: Hydra vulgaris, contig meta_s26021 AAAATCGATTTGTAAAATGAAGACAGTGTTTGCAATTTTGTTTTTGGCGTTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAATTGAAAAAGAAATACTTGAAGATCTTGAAGAGGAAAGTGACGAATTAAATGATAAAGTAAGAATCAATGATGCAAAGCCATGGAGATGGGTACAGAATACGATGGAGGAACTTGTTCCTATATACCAGCTGTTGTTGCGGCGGCTGGTAAAAAGTATAGAATAACTAAGATAAAACTTTTATCATATCAGCTTATATAAAATTGTATCAAGTTATGTTGTTATCGGTATTTAATATTAAATACTTTGATTTTTAAATATTTTAAAACTACGTTTTTACGCTATTACCGTAAAACGTTTTTGTATTTTTATAAACTAACTCCATG

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>Arm2b2_45058 ENA|HAAC01045058.1 TSA: Hydra vulgaris, contig miradenovo_rep_c85156 AGAGATGAGATGTCATAGACAACTAATCTCAAGAATGTTTACTGTCCTTAAATAAAACACGTGATGTTTTCCAATCGGCTGGTATAAAAACTGTGTCACTTTCTTTTTTGAAATCGATTTGTAAAATGAAGACAGTGTTTGCAATTTTGTTTTTGGCGTTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAGGAAGAAATTAAAATGAAATTGAAAAAGAATACTTGAAGATCTTGAAGAGGAAAGTGACGAATTAATGATAAAAGTAAGAATCAATGATGCAAAGCCATGGAAGAATAAGGGTAAACAAAG

>Arm2b3_30861 ENA|HAAC01030861.1 TSA: Hydra vulgaris, contig meta_s29905 AGATGAGATGTCATAGACAACTAATCTCAAGAATGTTTACTTTCCTTAAATAAAACACGTGATGTTTCCAATCGGCTGGTATAAAAACTGTGTCACTTTCTTTTTTATGAAATCGATTTGTAAAATGAAGACAGTGTTTGCAATTTTGTTTTTGGCGTTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAATTGAAAAAGAAATACTTGAAGATCTTGAAGAGGAAAGTGACGAATTAAATGATAAAAGTAAGAAATCAATGATGCAAAGCCATGGAGATGGGTACGAAGAATACGATGGAGGAAACTTGTTCCTTATATACCAGCTGTTRTTGCGGCGGCTGGTAAAAAGTAATAGAAATAACTAAGATAAAACTTTTTATCATATCAGCTTATATAAAATTGTATCAAGTTATGTTGTTATCGGTATTTAATATTAAATACTTTGATTTTTTAATATTAAAAACTACGTTTTTGCTTATCCGTAAAACGTTTTTGTATTTTTATAAACAACTCC

>Arm2bl1_39160 ENA|HAAC01039160.1 TSA: Hydra vulgaris, contig miradenovo_rep_c46426 GGGGGGGGGGGGGACTCAGTGAAATCGATTTGTAAAATGAAGACAGTGTTTGCAATTTTGTTTTTGGCGTTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAATTGAAAAAGAAATACTTGAAGATCTTGAAGAGGAAAGTGACGAATTAAATGATAAAAGTAAAGAAATCAATGATGCAAAGCCATGGAGATGGGTACGAAGAATACGATGGAGGAAACTTGTTCCTTATATACCAGCTGTTATTGCGGCGGCTGGTAAAAAGTAATAGAAATAACTAAGATAAAACTTTTTATCATATCAGCTTATATAAAATTGTATCAAGTTATGTTGTTATCGGTATTTAATATTAAATACTTTGAAAATTTTTTATTAAAACTACG

>Arm2bl2_02135 ENA|HAAC01002135.1 TSA: Hydra vulgaris, contig asmbl_18790 AAGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAATTGAAAAAGAAATACTTGAAGATCTTGAAGAGGAAAGTGACGAATTAAATGATAAAAGTAAAGAAATCAATGATGCAAAGCCATGGAGATGGGTACGAAGAATACGATGGAGGAAACTTGTTCCTTATATAGCAGCTGTTGTTGCGGCGGCTGGTAAAAAGTAATAGAAATAACTAAGATAAAACTTTTTATCATATCAGCTTATATAAAATTGTATCAAGTTATGTTGTTATCGGTATTTAATATTAAATACTTTGATTTTTAATATTTAAACTACGTTTTCGCATCCGAAAACGTTTTTGTATTTTTATAAACAACTCCATGATTAAACAGAATGATTTTAATAG

>Arm2bl3_30236 ENA|HAAC01030236.1 TSA: Hydra vulgaris, contig meta_rep_c29539 CTTTTATCATTTAATTCGTCACTTTCCTCTTCAAGATCTTCAAGTATTTCTTTTGCAATTTTGTTTTTGGCGTTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAARGAAGAAATTAAAAATGAAATTGAAAAAGAAATACTTGAAGATCTTGAAGAGGWAAGTGACGAATTAAATGATAAAAGTAAAGAAATCAATGATGCAAAGCCATGGAGATGGGTACGAAGAATACGATGGAGGAAACTTGTTCCTTATATACCAGCTGTTATTGCGGCGGCTGGTAAAAAGTAATAGAAATAACTAAGATAAAACTTTTTATCATATCAGCTTATATAAAATTGTATCAAGTTATGTTGTTATCGGTATTTAATATTAAATACTTTGATTTTTAATATTTAAACTACGTTTTCGCATCCGAAAACGTTTTTGTATTTTTATAAACAACTCCATGATTAAACAGAATGATTTTAATAGAACCTT

>Arm2bl4_45015 ENA|HAAC01045015.1 TSA: Hydra vulgaris, contig miradenovo_rep_c84963 TATCATTTAATTCGTCACTTTCCTCTTCAAGATCTTCAAGTATTTCTTTTGCAATTTTGTTTTTGGCGTTCATTGCGTTGACATACGCAAGAAGTTATGAGGATGTGAAGGAAGAAATTAAAAATGAAATTGAAAAAGAAATACTTGAAGATCTTGAAGAGGGAAAGTGACGAATTAAATGATAAAAGTAAAGAAATCAATGATGCAAAGCCATGGAGATGGGTACGAA

>Arm3b1_44434 ENA|HAAC01044434.1 TSA: Hydra vulgaris, contig miradenovo_rep_c81907 AATCAATTTTTTAAAATGAAGATAGTGTTTGCGATTTTTGTTTTTGACATTCATTGCGTTGACATATGCAAGAAGTTTTGAAGATTTAAAAGAAGAAATTAAAAATGAAATCGAAAAAGGAAATATTTGATGACCTTGAAGAGGAAAGTGACGAATTAGATAATAATGTTAAAAAATTCAATGATGCAAAGCCATGGAGACGATGGTTTCGATGGAAGAATATTGCTCCTTTAATACCAGTTGTTATTGCGGCATCTAGGTAAAAAGTAATACGAAACAACTAAAATTTTAATTGATATGAATAAAACTTTTTATCATATCAGCAAATTGTTAATTTAGTTTTAAATCTATTTTTTGTTATTTTTCTTATTCTGTTAGTTAATTGTAA

>Arm3b2_30807 ENA|HAAC01030807.1 TSA: Hydra vulgaris, contig meta_s29277 AAAAAAAAATCAATTTTTAAAATGAAGATAGTGTTTGCGATTTTGTTTTTGACATTCATTGCGTTGACATATGCAAGAAGTTTTGAAGATTTAAAAGAAGAAATTAAAAATGAAATCGAAAAGGAAATATTTGATGACCTTGAAGAGGAAAGTGACGAATTAGATAATAATGTTAAAAAATTCAATGATGCAAAGCCATGGAGACGATGGTTTCGATGGAAGAATATTGCTCCTTTAATACCAGTTGTTATTGCGGCATCTGGTAAAAAGTATCGAAACAACTAAATTTAATTGATATGATAAAACTTTTTATCATATCAGCAAATGTAATTTGTTTAAATCATTTTTGTATTTTCTTATCTGTAGTTAATTGTAATATTAGATACTTTGATTTCATATAATTAAAACTT

>Arm3b3_30828 ENA|HAAC01030828.1 TSA: Hydra vulgaris, contig meta_s29473 AAAAATCAATTTTTAAAATGAAGATAGTGTTTGCGATTTTGTTTTGACATTCATTGCGTTGACATATGCAAGAAGTTTTGAAGATTTAAAAGAAGAAATTAAAAATGAAATCGAAAAGGAAATATTTGATGACCTTGAAGAGGAAAGTGACGAATTAGATAATAATGTTAAAAAATTCAATGATGCAAAGCCATGGAGACGATGGTTTCGATGGAAGAATATTGCTCCTTTAATACCAGTTGTTATTGCGGCATCTAGGTAAAAAGTATCGAAACAACTAAATTTATGATATGATAAAACTTTTATCATATCAGCAAATGTAATTTGTTTAAATCATTTTTGATTTTCTTATCTGTAGTTAATTGTAATATTAGATACTTTGATTTC

>Arm3b4_02138 ENA|HAAC01002138.1 TSA: Hydra vulgaris, contig asmbl_18794 TAAGATTGGGTAGCTTTAGCCCTAAATAGGGATGACTTTAGTCCAAGCAAAGTTTTTGTTTAAAAATGGTTTAAAATTGATACCTCAAGGTTTTGAAGATTTAAAAGAAGAAATTAAAAATGAAATCGAAAAGGAAATATTTGATGACCTTGAAGAGGAAAGTGACGAATTAGATAATAATGTTAAAAAATTCAATGATGCAAAGCCATGGAGACGATGGTTTCGATGGAAGAATATTGCTCCTTTAATACCAGTTGTTATTGCGGCATCTGGTAAAAAGTAATCGAAACAACTAAAATTTTAATTGATATGATAAAACTTTTTATCATATCAGCTAATGTAATTTGTTTTAAATCATTTTTGTATTTTCTTATCTGTAGTTAATTGTAATATTAGATACTTTGATTTCAT

>Arm3b5_42749 ENA|HAAC01042749.1 TSA: Hydra vulgaris, contig miradenovo_rep_c70863 TGCTATTTTTCATCCGCTTGTATAAAAACTGTTTCACTTTTAATTCTTAAAAAATCAATTTTTAAAATGAAGATAGTGTTTGCGATTTTGTTTTTGACATTCATTGCGTTGACATATGCAAGAAGTTTTGAAGATTTAAAAAAAGAAATTAAAAATGAAATCGAAAAGGAAATATTTGATGACCTTGAAGAGGAAAGTGACGAATTAGATAATAATGTTAAAAAATTCAATGATGCAAAGCCATGGAGACGATGGTTTCGATGGAAGAATATTGCTCCTTTAATACCAGTTGTTATTGCGGCATCTGGTAAAAAGTAATCGAAACAACTAAAATTTTAATTGATATGATAAAACTTTTTATCATATCAGCTAATGTAATTTGTTTTAAATCTATTTTTGTATTTTCTTATCTGTAGTTAATTGTAATATTAGATACTTTGATTTCATATAATTAAAAACTTAAACGT

Antimicrobial peptides (AMPs): Hydramacins>HYDMA1a_Hydvu ENA|HAAC01030871.1 (Hydramacin-1) 81 AAs N-term different than ENA|HAAC01030787MFLFLLSIFWFALMPSDTQAGTLLGCWETWSRCTKWSQRGTGILWKNCNNRCKELGHGYGVCEKGNQNVVFLKNAWACICY

>HYDMA1b_Hydvu ENA|HAAC01030787.1 (Hydramacin-1) 80AAs identical to >HYDMA_Hydvu sp|B3RFR8|HYDMA_HYDVU Hydramacin-1 OS=Hydra vulgaris PE=1 SV=1MFHFCIYFLVALMPSDTQAGTLLGCWETWSRCTKWSQRGTGILWKNCNNRCKELGHGYGVCEKRKSKCRFSKNAWACICY

6



>HYDMA1c_Hydvu ENA|HAAC01045032.3 (Hydramacin-1) 93 AAs N-term and C-term different / ENA|HAAC01030787MRSIVCFIFVSIFLVALMPSDTQAGTLLGCWETWSRCTKWSQRGTGILWKNCNNRCKELGHGYGVCEKRNPKCRFSKNAVGLASVTKFYLTTY

>HYDMA1d_Hydvu ENA|HAAC01044958.3 (Hydramacin-1) 89 AAs N-term and C-term different / ENA|HAAC01030787MRSIVCFIFVSIFLVALMPSDTQAGTLLGCWETWSRCTKWSQRGTGILWKNCNNRCKELGHGYGVCEKGSKCRFQNAWLASVTNSINHI

Antimicrobial peptides (AMPs): Periculins>Peri3_17218 Hydvu ENA|HAAC01017218 (no PTHR): (Periculin 3) Hydra vulgarisMFMKIILIFSVILAATADEFLEFEDQYESSDTIPSNFDNENQFETKIDYFPKSEYKPKKIFCLGVDVTKKCLERADGNYAIDSKTKPGYVACVDMNPICMPCPYGMVFCDKTGNKGLGQCLRQCPPRSY

Antimicrobial proteins: LBP>LBP_Hydvu ENA|HAAC01032207_3 (PTHR10504:SF73, PROTEIN C05C9.1): LBP identical to PREDICTED: lipopolysaccharide-binding protein-like [Hydra vulgaris] Sequence ID: ref|XP_002170771.2| Length: 313 Number of Matches: 1; 26% identical, 47% similar to bactericidal/permeability-increasing protein precursor [Xenopus (Silurana) tropicalis] Sequence ID: ref|NP_001107736.1| Length: 476 Number of Matches: 1; Uniprot: P18428 (LBP_HUMAN) Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria, and acts as an affinity enhancer for CD14, facilitating its association with LPS. Promotes the release of cytines in response to bacterial lipopolysaccharideMINLLLLVFLLIVVLGFSLCENPGIQLKLTENGIKYAVKEGLPYLRDDLLSEMINYNGESGNLEFKLQNLHMSKIDFGEVFLTPISGRGIKCSVNIDIIEAVGIFFYNYKTIFGINIHDTIGFNVNISNVESALSVEIGSNKDGRPSINFFDCSLKINSLTVQMNGKDKWLYDLINPLVESTLEIVFSQLFCNIVKTKVEENIKNKLATFTEIINIDSLAKIDLSLTQPPNFTDNYVQFFFKGKFLLQNDSSLNQFLLSQPTVSDEDTQMLYLWITDYTINTAAEVYHKGGALTQEIYSWDPKTPKDLQKFLQTSTFTLFFPGLLKYGGEKMALFIRSYKPPQVLIEKDDFKINLFTEGMFKVRDNDLTLDAFLIKFDIKAVAEIFVSNNKITAKISAFDYDAVVVRSYVGSALIPLDSFLIKKLVDAAIIKNANSFLDNGFSLPPIRGNEITNLNIKLLKNTVQVGGDVHSSAENMVNSVLRNNMIFK*

B-cell Translocation Gene: BTG1>BTG1_Hydvu ENA|HAAC01008873.1 TSA (PTHR22978, B-CELL TRANSLOCATION GENE): Hydra vulgaris, contig asmbl_7524_ext: 966, 64, 1030 (+) length 322; identical to uncharacterized protein LOC100201130 [Hydra vulgaris] Sequence ID: ref|XP_002164940.2|; 42% identical, 62% similar to BTG1 Gallus gallus >gi|45384374|ref|NP_990681.1| protein BTG1 [Gallus gallus] B-cell translocation gene 1, anti-proliferative (The tob/btg1 is a family of proteins that inhibit cell proliferation, see refs in P62324 (BTG1_HUMAN)MHYEINCAVKYIVSKIKEYSSLLNEEQLEKFESRLNQLLKEKYESHWYEDKPMKGSAFRCINISVEDNSVDSVLRKAAEEVSLNSQNLLEIFNDGLALWVDPNDVSCRLGKGAIFPVYKKIAERKSKPLNSNAPEFSLKQRPRSTSPPITFNNKDFYVKTRSLTPPGFSSTDVTIENISIPTSSTSKDTDIHKLWDSIPNKTYPIAGSSYSGHYLNNSQVKNVPVSSLYFNGSDNISTAQNSYIDQSHQSVSYRQGDSSYSFNQYSSYYNPSYWKKNIGPLYNQPLNLQQDDQTYQRYHWSRNKIPGNMSSVYSTARAQEVF

CHAPERONES: Calreticulin, CRYABs (HSP20), DnaJB9 (HSP40), HSP16, HSP90>CALRC_Hydvu ENA|HAAC01018675_2; calreticulin-like [Hydra vulgaris] (no PTHR) Sequence ID: ref|XP_002161300.1|Length: 421; Calreticulin (CRT) is a multifunctional protein that binds Ca2+ ions rendering it inactive. Ca2+ is bound with low affinity, but high capacity, and can be released on a signal (see inositol triphosphate). CRT is located in storage compartments associated with the endoplasmic reticulum. CRT is expressed in many cancer cells, plays a role to promote macrophages to engulf hazardous cancerous cells. Can be nuclear, bonds to nuclear receptors and homeodomains. MMSVTIFVLAFIAFAQCTVYFKDTFDDETWEKRWIHSKSKGGDAGKFKLSSGKFYGDKARDQGIQTSQDAKFYQVSAKVPNPFSNEGKTLVLQYQVKHEQNIDCGGGYIKLFPSTITPETMNGDSPYHIMFGPDICGPGTKKVHVIFTYKGKNLLTKKDIRCKDDEMTHLYTLIVKPDNTYEVRIDGSKVESGTLEGDWDFLPPKRIKDPSLSKPADWVDEAKIDDPEDKKPEGYDKPELIPDKDATKPEDWDAEEDGEWEPPMINNPEYKGEWKPRKIDNPAYKGEWVHPEIDNPEYKSDDNLYKYDDIGYIGFEIWQVKSGTIFDNIIVTDDIAEAEKFAKETFEKTKVEEKQMKDKIEEEERKKREEEEARTKKEEEEKKKIEKEEEEEDDEDTKEDTKEEEKPAVEDSTDDTVKDEL*

>CRYAB1_Hydvu ENA|HAAC01018571.1 TSA (PTHR11527, SMALL HEAT-SHOCK PROTEIN (HSP20) FAMILY): Hydra vulgaris, contig isotig01482; Uniprot: T2MHG6 (T2MHG6_HYDVU); 99% identical to gi|221114177|ref|XP_002166332.1| PREDICTED: alpha-crystallin A chain-like [Hydra vulgaris] but actually more related to the alpha-crystallin B chain in bilaterian speciesMSLWHVPVHKYFQTDPFLDDLLEITFPPTRYYPLFNVGANAVSKKKASPKEKGFVVNLDVKHYKPEEVALKVEGQVLEVSGKHRNENENGFESSEFHRKYTIPDDVDVAALTSNISQDGILHIEAPKKLPVTSESGESTKETFKCTLDVQGFKPEEISIQVKGRDLVVHGETKTENSGEHGSSYHHKQFTKHVALPDDVDPSELCSRYTKDSKLTIEAPRKQLQAPLKLEIKMEE

>CRYAB2-Hydvu ENA|HAAC01043011.1 TSA (PTHR11527, SMALL HEAT-SHOCK PROTEIN (HSP20) FAMILY): Hydra vulgaris, contig miradenovo_rep_c72611: 777, 59, 836 (+) Uniprot: T2MHG6 (T2MHG6_HYDVU); identical to >gi|449677322|ref|XP_002158752.2| PREDICTED: alpha-crystallin B chain-like [Hydra vulgaris]; Uniprot Human CRYAB E9PNH7: Belongs to the small heat shock protein (HSP20) familyMSLWHVPVHKYFPTDPFLDDIMEITFPPLRYYPLFDIGTNVLPKKKSSKKEDGFYANLDVKHYKPEEVTLKVEGQTLEVSGKHRNENENGFECSEFHRKYTIPDDVDPTALTSNISQDGVLHIEAPKKLPVTPDSGESTKETFKCALDVKGFKPEEISIQVKGRDLVVHGESKTENSGEHGLSFHHKQFTRNISLPDDVDPAHLSSRYTKDSKLTIEAPRGQVQAPLKLEIKWKNEVFLNFLDFLFNNVVFFLLAIFTS

>DnaJB9_Hydvu ENA|HAAC01042048.1 TSA (PTHR24077, FAMILY NOT NAMED): Hydra vulgaris, contig miradenovo_rep_c66808: 726, 1, 727 (+); identical to >tr|T2M3D2|T2M3D2_HYDVU DnaJ homolog subfamily B member 9 OS=Hydra vulgaris GN=DNAJB9 PE=2 SV=1; chaperone; DnaJ (Hsp40) homolog, subfamily B, member 9; ER-associated ubiquitin-dependent protein catabolic process; Involved in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. Acts as a co-chaperone with an Hsp70 protein, see Q9UBS3 (DNJB9_HUMAN)KKLFSKKMRLDYIILTFTCISIKELFASTKDYYKILGVSRNASDRDIKKAFRKLALKYHPDKNKSKDAESIFRDIAEAHEVLSDEKKRKIYDQYGSEGLKEKAGFDGSAFHFDFSDFFKDFGNFGGRKSSNSNKFSFNFGSFFDNDDEDTDSFFGNQFHQTHRNSGEDSVFSKSDDSFFGGFGDSMFGSFGSNSMFSESHSFSESRQQGRRCKTITKKMGNMVIDHNRVFLNIIDNDRVVYT

>HSP16-2a_Hydvu ENA|HAAC01029610.1 TSA (PTHR11527, SMALL HEAT-SHOCK PROTEIN (HSP20) FAMILY): Hydra vulgaris, contig meta_rep_c24088 ; identical to >gi|221106831|ref|XP_002160804.1| PREDICTED: heat shock protein Hsp-16.2-like [Hydra vulgaris] (related to the bilaterian alpha-crystallin B chain)MSLWHIPVHKYFDTDPFLDDIMEITFPPLRYFPXFNVGTXAVSKKKTPKXXGFVVNLDXKHYXPEEVTLKVEGQVLEVSGKHRNENENGFESSEFHRKYTIPDDVDVTALTSNISQDGVLHIEAPKKLPATSGESTKETFKCTLDVQGFKPEEISIQVKGRDLVVHGETKTENSGEHGSSFHHKQFTKHVALPDDVDPSELSSRYTKDSKLAIEAPRKQLQAPLKLEIKMEE

7


http://www.ncbi.nlm.nih.gov/protein/449687644?report=genbank&log$=protalign&blast_rank=1&RID=JFKMN1FS014


>HSP16-2b_Hydvu sENA|HAAC01029723.1 TSA (PTHR11527, SMALL HEAT-SHOCK PROTEIN (HSP20) FAMILY): Hydra vulgaris, contig meta_rep_c24776 isoform of HSP16-2aMYFLFKLVGSLRKMFKIFHSLLFFFLFVNLVCRCLGQVLEVSGKHRNENENGFESSEFHRKYTIPDDVDATALTSNISQGGVLHIEAPKKLPASSGESTKETFKFSLDVQGFKPEEISIQVKGRDLVVHGETKTENSGEHGSSYHHKQFTKHVALPDDVDPSELCSRYTKDSKLTIEAPRKQLQAPLKLEIKMEE

>HSP90a1_Hydvu ENA|HAAC01030048.1 TSA (PTHR11528, HEAT SHOCK PROTEIN 90): Hydra vulgaris, contig meta_rep_c27628; 98% identical to gi|221115825|ref|XP_002165028.1| PREDICTED: heat shock protein HSP 90-alpha 1-like [Hydra vulgaris] (PTHR added manually)MVEGGEIETFAFQAEIAQLMSLIINTFYSNKEIYLRELISNASDALDKIRYLSLTDPTVLDSGSELKIDIIPNKEEKTITIFDTGIGMTKADLVNNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVADKVEVITKNNDDEQYIWVSSAGGSFTVQRDTVNEPLGRGTKIILHMKEDQLDFSEEKKVKDIIKKHSQFIGYPINLRVQKTRDKEVSDDEAEDEEKKDKSEEKMEDEDEDEPKIEDVGDDAEAEKKDKKKKKKIKENYTEMEQLNKTKPLWTRNPDDISSEEYADFYKSLTNDWEEHLAVKHFSVEGQLEFRAILFVPKRAPFDLFENKKQKNSIKLFVRRVFIMENCEEVMPEWLXFVKGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKXLELFAEISEDKDNYKKFYEQFSKNIKLGIHEDSQNRTKVADLLRYHSSASGDDLTSLKDYVSRMKENQKDIYYITGESKEIVSSSAFVEKVKKNGFEVLYLIDPIDEYAVQQLKEYDGKKLVCVTKEGLELPVSDDEKKRQEELKASFEELCKVIKDILDKRVEKVTVSNRLVDSPCCIVTSTYGWSANMERIMKAQALRDTSTMGYMAAKKHLEINPEHSIMVALKKKVDADKNDKSIKDLIVLLYETSLLSSGFSLEDPQNHAARIHRMVKLGLGVDEDESAVEEIATDDMPPLEGDSRKRRRQSQNRKKSTNSNFRDN

>HSP90a2.1_Hydvu HAAC01045038_1 (HyHSP90) (PTHR11528, HEAT SHOCK PROTEIN 90): 99% identical to heat shock protein HSP 90-alpha 1-like [Hydra vulgaris] Sequence ID: ref|XP_002165028.1| Length: 722 Number of Matches: 1 (51/301 – 472/722); shorter isoform of HSP90a1_HydvuMLVMMQKLRKKTKRKKRKLRKIILKWNNSTKLNHCGLETQMILALKSMLNFYKSLTNDWEEHLAVKHFSVEGQLEFRAILFVPKRAPFDLFENKKQKNSIKLFVRRVFIMENCEEVMPEWLNFVKGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKCLELFAEISEDKDNYKKFYEQFSKNIKLGIHEDSQNRSKVADLLRYHSSASGDDMTSLKDYVSRMKENQKDIYYITGESKEIVSTSAFVEKVKKKGFEVLYLIDPIDEYAVQQLKEYDGKKLVCVTKEGLELPVSDDEKKRQEELKASFEELCKVIKDILDKRVEKVTVSNRLVDSPCCIVTSTYGWSANMERIMKAQALRDTSTMGYMAAKKHLEINPEHSIMVALKKKVDADKNDKSIKDLIVLLYETSLLSSGFSLEDPQNHAARIHRMVKLGLGVDEDESAVEEIATDDMPPLEGDSEKDEDKARMEEVD

DODE proteins (Hydra species-restricted)>DODEl1_Hydvu ENA|HAAC01039060.1 TSA (no PTHR): Hydra vulgaris, contig miradenovo_rep_c45769; 97% identical to gi|526252906|ref|NP_001267810.1| DODE [Hydra vulgaris] >gi|316995498|gb|ADU79235.1| DODE MMTQNISSLTKXKLAQCLAEIWKEFAEEIPLPKYKIASIEQEXKLLVERAHRVLTFWYQSDPDAFNENNIKMKLKSLKRNDIIRAVFGEEDDQPAKPKETNVSKVEDLSYRQIRVLSDFLDPDYGWEEFAHHLFEHDNEMINEIQKLRHEYAGGGNPAYLFLKQLLQRRPNILLNEFLDACKEVKRADIIHYANENFSGISYISELDKNQLRDFADKVRGNIVPSNWAEIASEFVEFSSEDIKRIELERLAPNSYSPTKKLFEKLKQIHPNMELDNLINVCEKIRRKDVANKLREFAINNSSIAQ

>DODEl2_Hydvu ENA|HAAC01028188.1 TSA (no PTHR): Hydra vulgaris, contig meta_rep_c16425; 90% identical to gi|449680734|ref|XP_002170368.2| PREDICTED: uncharacterized protein LOC100209127 [Hydra vulgaris]MNQNISSFTLLKLTECLSECWRELAEEIPLSSYKITAIDNEETQLVEKAHRVLYSWFQLAPDTFNENNIKMKLKSIQRIDIINDVFGEVDDRLMKPKVTFVPKVEDLSYRQIASLSDLLDPEYGWEEFAYNLFECDNEMINEVLKLRFDYAGGGNPAYKFLKLLLQRRPTIRLNEFLDACKQVQRADIVYYANENFSKVCYINELNKRQLKEFADKIRGNVIPSNWAEIASEFREFSAKDIKRIELERMAPNSYSPTKKLFEKLQQTHPKMELKKLISVCEKIRRKDVANKLSEFAKNNEQLSSS

Fatty acid metabolism>ACSF4l_Hydvu ENA|HAAC01012869.1 TSA (PTHR24095:SF43, ACYL-COA SYNTHETASE FAMILY MEMBER 4): Hydra vulgaris, contig CUFF.17280.3: 2625, 1, 2626 (+); 100% partially identical to >gi|449664050|ref|XP_002164171.2| PREDICTED: acyl-CoA synthetase family member 4-like [Hydra

vulgaris] from 1/185 -> 302/486 and 481/487 -> 870/876; Q4L235 (ACSF4_HUMAN) alternative name: Aminoadipate-semialdehyde dehydrogenase (AASDH); Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA; Ubiquitously expressed in adult tissues; Belongs to the ATP-dependent AMP-binding enzyme familyMQESDVIFVSSALTFDASIVQIFLGWCSFSTLLVVTDKLRSHPEKISKCLEKHAVTFLQCTPSFLGLIGSHFQEKYLFYNGSKLKILVLGGESFPSKEKCGKWKKALPQLRLFNLYGTSEVSAWASIYEVTNDQFHTERQTLDSDWVPIGKPLSKTIIKVNDLYGNALKHGLGKIWIGSEERVCRITESEEPAFDSCIMRATGDLGFIEGEQIYYSGRYDDQIKRNGLFISTIHINNIVRDIPGVKDCFSTVDKEINNILIVYYVPENDIKVNIFEFMLTRYPSQYIPDKIASVDCFPLTMHGKIDKNALRKKLKNVSNWNLNDIIRNITKSWNEALKISPGDSVSAEIEFSILGGNSFIAAYLVNKFLDFFPYQINFEEIFIKILTSSLNQFIHFISSYVHVDVKNNIEDKASYIVKFDGERCKCFDKDKCFCNKLVKCNCFTSFLKAHTIQTCMCPKKYLGFQNNNFLTSKFNISLSLEWKFDTQKCVDASPLLVFYDNSSDGIVYIGSHSYIFVALNLKDGKLLWRQILGGRIESSAIVSPDGKFICVGCYDGFIYALHYGTGEIYYKFKTNDIVKCTPAPSKKHRLIIVGSYDKHIYALDVAQKVCKWKIKFNSSCFASPLIIDEQNIVIVALLSGSLCSINAETGEKIWEINFNDKPLFSSPTLCRNLILIGCVDGNLYAIDLNGKKLWNFTTKAPIFSSPLIIYEREALIFIGSNDQIIYCLNEQGFLLWKYKTSSSIFSSPSVLHVSSLENNMLQFEISVVILVSSTDGHVCALKFEYYPQYELQSKFSIEHAAKIKSKDTVNEKLPIDSTERLFVSDTTVIEVSCIGAYKFPAEIYSSPIVCNNKIIVGCRDNNVYCMNIEL

>ALOX5_Hydvu ENA|HAAC01041900.1 TSA (PTHR11771:SF39, Lipoxygenases, sub-family not named): Hydra vulgaris, contig miradenovo_rep_c65759; 77% identical, 85% similar to arachidonate 5-lipoxygenase-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002157326.2| Length: 623 Number of Matches: 1; 23% identical, 41% similar to arachidonate 5-lipoxygenase, isoform CRA_a [Homo sapiens] Sequence ID: gb|EAW86642.1| Length: 529 Number of Matches: 1MYTFEFLLVLYFATVNGGYRNNGNYVTSQKESLVNYYKNSLYGTFNEQKCDLSDHCIVSLPSSINQRKCKLKKCFSNYQKNKNLRNNRCMEARKSDVLFARKWYSITDGSTLSRSEFPFKDVPFLNQSLRDVNFYTAINPIESSWLMLLQTWINGLMKPTSDKIKSVFNNTNLHNIEAYRQLKAAFEASIRSFNTPQYFDKPSLYPQTFTDLSFGELWKSNDIFAQRRLAGSCPFHLRKVTKSGEIGFSDKTLFSLLNKNYNFNEFINHASGGSIKSMSQAIQEGALFILYHDSYNDIVTQPDNLNKDQTVLGKNRTVMNNTSPVTLFVLVKGEFKVAAIQIDYKPNSTVYSPSSPIDQWLLARAMVEMTDQDVCDAKVHLGFLHLHASIFCLSFSRHLSTQHPLYDLFKWHCYGTVPALSLNYPTLYSNNFLPYAMGNKGFLKLSKIGFDEAYYGQYDLEQHLKRQGLDDTRIKYYPYRDDARVISKELLDFSIKVVNLYYKDNKDVINDVELQSFANELSIDGTVKPDGGKGKVKRFPSSFNKKIELVNFLHQFLWFNILHSVSNYAHGHSFVPVKPTKLYHDRNFENNYLYNLPDIDTAVEAIRLSVSLDSFRANRLMDYSDKVQDKKFKELVQQTYCVLNSKVQKILEQNNAKRKAAGQLTFQYVEPKWLTNSIHCLVSN

8



GTPases Ras family (DiRas1; Rhes-like; Ras-ERGI)>DiRAS1l_Hydvu ENA|HAAC01014429.1 TSA (PTHR24070:SF211, RAS-DVA-2 SMALL GTPASE-RELATED): Hydra vulgaris, contig CUFF.3941.1: 669,

221, 890 (+) 207 residues; besthit: TR:Q0VFI1_XENTR, DIRAS1 from Xenopus tropicalis 2.4 e-18, score 242 (DIRAS family, GTP-binding RAS-like 1, 198 residues) 35% identical, 54% similarMQTRRQGNAKSRRNALKTLRKRDCVGLLLVGKCETGKSSLVNRWINGDYKDYYIPTVEEFYLKSYGVMGHSVNVGVIDMSGSWDFPGMLDLYFNKADSIIFVYEVNNKVSISEMFLFYQRLLKIRGENHEVYMSVVGTKMDKQQQYDENTKNEAVDAFIKEIGGRAKHTITSAKLNINVVEAFEAALSNVVANMTPNEDAIKRLDKL

>Ras-ERGI_Hydvu ENA|HAAC01019550.1 TSA (PTHR24070, FAMILY NOT NAMED): Hydra vulgaris, contig isotig10260: 561, 233, 794 (+) length 187; identical to >gi|449691046|ref|XP_004212542.1| PREDICTED: uncharacterized protein LOC101236724 [Hydra vulgaris]; 34% similar, 54% identical to ras-related and estrogen-regulated growth inhibitor-like [Musca domestica] ref|XP_005180801.1|; MSLNSLGYNIRLTVNGFKGTGKTTLIQTLFGNSLSQDLTVHLKEDFYSDKKVKQNIVESDGRNEAVTSWAHGVVIMVSTSSLISFMYAEDFIIRAKEITLKNAPIVLVVNNKDELNRKVSLTDCIKLANKYDCKMYELSAQNDVKLVKELFKDICIEIVSKTRRRSKTVKTCPVKKAPSILRKMLTF

>Rit2l_Hydvu ENA|HAAC01008180.1 TSA (PTHR24070, FAMILY NOT NAMED): Hydra vulgaris, contig asmbl_4775: 648, 53, 701 (+); identical to GTP-binding protein Rit2-like [Hydra vulgaris] Sequence ID: ref|XP_002164337.1|; related to the mammalian neuronal GTP-binding protein Rit2 P70425 (RIT2_MOUSE)MEESFEKLKNIVFRREKEPIRIVVLGSPGVGKTALIIRCLTNQFFNHYVPGKEEAYKYTVNVGANKAQLDIMDSKGKNTALISHADAVILVYSVIDKESFENIKTLIKNVRDLNLNNIPIIVVGNKNDLPKKRQVSKTDAGLLSASYNVKVFESSAAVPVHDVRNIFAEVCRLVFEEKKERRESDPTDPLRRMTLNDITRKNSLSLDSTDFIKLVL

>RsmAl_Hydvu ENA|HAAC01005216.1 TSA (PTHR24070:SF17, RAS-LIKE PROTEIN 2): Hydra vulgaris, contig asmbl_31615: 771, 109, 880 (+), 257 residues GTPase Rhes-like; besthit TR:F1A0N3_DICPU RsmA, RAS family GTPase OS=Dictyostelium purpureum GN=rsmA, length 218, score 177, 1.9 e-11, 27% identical, 49% similar; besthit vertebrates; TR:Q2LIW6_TAKRU length 206, 52% similarMKEQCSANKIFTKEDCCTNMNKTTHCRKFNSRNEKKRRKIVIIGSPKCGKSALVERFLNNSYCDIPHNKKLKRANEDYYYKGYSLNIELVVVSENESTENKVFHIKTADAIMLVYEFASLNSVENLLQSYKAIRTVREDKMPVLIVSTKIDKNGGSSPQLHLRENESITSVLYAVRGAKQIYTSAKYNINIRDAFEMCFDDIIKRIHTWSMSAQQYSSMDERMSNRLALSEEPNKLFLFRRFLSMCNVKKRENDSKV

KINASES: CAMK Ser/Thr protein kinases >SIK2l1_Hydvu ENA|HAAC01028727.1 TSA (Ser/Thr protein kinase Sik2, PTHR24343:SF145): Hydra vulgaris, contig meta_rep_c19340: 2331, 1, 2332 (+) length 750; identical to >gi|449686119|ref|XP_002154971.2| PREDICTED: serine/threonine-protein kinase SIK2-like [Hydra vulgaris]; 42% identical, 57% similar to ref|XP_006510329.1| PREDICTED: SIK2 [Mus musculus]; Salt-inducible kinase 2 (SIK2) Uniprot Q9H0K1 Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators.MKYSVGMIIPKYCLLPLHEVSTKKENDIFGLNVEKYYPTMECNRDFKKQPVRIGLYDIEETIGKGNFAVVKLAKHRMTKSRVAIKIIDKSRLDESNLIKIKREVQIMKLLEHPNVLKLYQVMETKNMLYIVTEYATKGEMFAYIDKHGKLQEHEARRLFWQILSAVEYCHKHKIVHRDLKTENLLLDENLNIKIADFGFSNYIEENELLKTWCGSPPYAAPEIFEGKEYDGPAIDIWSLGVVLYVLVCAALPFDGETVHEVRDRVLEGRFRVPYFMSSELEDLIRKILVKNPIHRYSLEQIKAHPWLYEYPEDRPPIYNSYTSYNETFNGELNKHVLDVMMGLGLDIEKTKKSLAVNGYDHLTAIYHLLSERLRPNRTSYPEQNNVTTRYRRASSMADQVIVKNSQGLPLSVTQHVIPAGIKIADKNKAGLQYALNELHIGEVEIPPDIINSSIPGCVKEFSPPPVPHNLLHPRLGHFSSSSTQKNIETVNEEGNDDTETKTENTPLRQRRGRRSAVDAIYHNHRRHTVQNPLVENETLFVPSNHPLLNKEFNDTPPDNGDLSNKLKIKIVEPTVHPEQTYVSMLINPEQTLHLSTVAHKSDLAFNIGRRASDGVNAPFKHLLYKSDNLYLKEYKELQRLQRSFTPEKIHQQSCQFKENTSLVHDWKLSPTSSQNELLMMKLQKMHLANIDNTLETVDSWDAPGPCRRPPTYRKFSSCVLPMPAPIRRRRAPVIDNILNNFDNSTESDIV

>SIK2l2_Hydvu ENA|HAAC01009375.1 TSA: Hydra vulgaris, contig asmbl_9480_ext: 306, 1094, 1400 (+); isoform of SIK2l1, identical to SIK2l1_Hydvu from 46 to 84: AYIDKHG -> RDLKMCIKFDFKNMRIYFCANWKYIFSLAFIEIFIAIYIFIVYINLFIPAYIDKHGKLQEHEARRLFWQILSAVEYCHKHKIVHRDLKVISPFRNFKKKKLITTIS

KINASES: MAPK Ser/Thr protein kinases >IkBKb_Hydvu ENA|HAAC01024646_2 (I-kappaB kinase beta, PTHR22969); identical to uncharacterized protein LOC100207607, partial [Hydra vulgaris] Sequence ID: ref|XP_002168505.2| Length: 1212 Number of Matches: 1; 33% identical, 53% similar to inhibitor of nuclear factor kappa-B kinase subunit beta isoform X5 [Homo sapiens] Sequence ID: ref|XP_005273551.1| Length: 674 Number of Matches: 1MENGKVYGNWKYEKQIGCGAFAKVSRWKNIKTDKELVVKQCNSVLSVQSRRRWNDEIKLLKRLERHKNLVEERDVPEEIIKALASPENLLGLESCECDLREVLSYTENCCGLIESMVLRVLEDVACGLNFLHEKNIIHRDLKPENILKGHKGDQVVYKIADFGFAKDLDRSMCKTVLGTQNYMAPELYESQSGYTKAADYWSFGTVIFECITGIRPFDLIKENKLKVICNKSDTEIWGCETPDGVKFYSDIPMPNRLCKSLTSSLKKWLQLVLCHDADKRGTTECFSMIKDILSINEIHLFDIMTCQETSYACKPGDTVQNLKLFIKQEFGIEAYDQYLVKLGSDFLSDQQCLENYVQRTEVVFVFRDNIDATYKINKDMPDRVKELLGHYEEIQKYHELLLKWSHCIYYCTKQSNNYDRLLEGKNALIKILKCRMETIDELKNELTELIIQNETGIHFFNKSLETDIQLYGTDVPQDEWLKAQTEITKSNDDASNLKSLLNDIFNLKSDVEKISVVNGNQFSNELKKIKERAESELYNLSKQKSNKVESNSATMFNIVLEMHSNEKPFIEFYFQLKQVMKTKEKMRNINAALLKKKCALIKFKNSILETQLCRQAKLRESVTPCV

>IkBKe_Hydvu ENA|HAAC01028731_3 (I-kappaB kinase epsilon, PTHR22969:SF16, FI05319P); identical to inhibitor of nuclear factor kappa-B kinase subunit epsilon-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002163247.2| Length: 342 Number of Matches: 1MNVVRQSLNYVWSVQEVIGNGATGTVYKCSAKKTGAPCAAKVFNSQADRRPYEVRIREIELLKKLSHPNIIKLMGLEQEIGSKATVLIMELCGSSLYEIIEEPENMFGVDDITLINIIQDVCAGMEYLKNSNVVHRDVKPGNILRADKGSGGYIYKITDFGAARELGEAEQFVSLYGTEEYLHPDIYEKAVMKWSSNKTFTSRVDMWSLGVTFYHLATGQLPFRPAGGRQNKDIMFKMISEKSNDAISCYQDLDNGSLIYSNELPKKTRISENLKMHLTPILKCLLQIQQQFMLSYDDFFKEIKELVSLKKIYVFCCGNFKLQNLYMDAREITATNLFQTLGITNGEIIFNEDFIDFSNLSSYETTVDNPFIILTNSMSCEKLLNEDLPQNINNDDLKFSKIHAGYAYDFKRKAENIILCCKLTKQIYRIVQRFFLESFKLFQEICKQKHYQIEFIKKQFIRLNKLLNLKDNFNSDLEMKIESQLKYDCVVSCFSEIQTLLKRILENMPLKMPTILNDSEPLLWLESISFLVKLNHSIFLKFYKDKYYKRAVATMLDELVHKTEKEKLQTNLLSLSEKLEWLIAYQISVEKDVIQRLSFFNEEKQKISALTTKLDQTFKILNNHFELESINFDDEMCKYISWSKNLVDFNKLQKQLELLENIMPELIVTANEQQQKLEYLENFDMIPSD

9



>IRAK_Hydvu ENA|HAAC01031412_1 (S/T PKC like kinase, PTHR23257) Protein Kinases (PKs), catalytic (c) domain in the C-term moiety; Deltablast

besthit: hypothetical protein CGI_10014308 [Crassostrea gigas] gb|EKC33317.1|Length: 784 Number of Matches: 3, 50% similar 2e-109; Serine/threonine-protein kinase CTR1 [Crassostrea gigas] gb|EKC33316.1|Length: 499 Number of Matches: 2: 53% similar 1e-108; serine/threonine-protein kinase TOUSLED-like isoform X2 [Aplysia californica] XP_005102047.1|Length: 747 Number of Matches: 2: 49% similar 2e-108, NO CNIDARIAN HIT among the first hits MPKTYVDNAYNRSVGRVGMVHGSAVIPSGSSGSRQSSSYSSYSSGSTASSNRSYVDNAYNRSVGRVGLEVGSMVISKNNSSSTPSNYYSNERTYVDNSFNRSVGRVGLDIGSMVISKNNDSSTKSNHHSNEKTYADNSFNRRVGRVGLEVGSMVISKKNDSSTKSNHHSNEKIYADNSFNRRVGRVGLEVGSMVISKNNDNPTQRNQQFPEKSQKTKKQEEKGMRAEAVKLTENDKSKKVYVDNAFNRRHGRVGLPLGSKPLRKKVEVVPLPTFPYEELCPQLNDYSGYDIKLQEIIQNLMDRRVIEKNLALESQELIPINTLQSFANISGKDVAYEELELIKKIGSGGFGEVYLSKWKDAIVAVKKLRLQRISKNRLKDFTKEVTNYYTLNHPNVVKFLGACTVTPNLCIIMEYMDMSLFEAKIDIDFSEEERLKIISQVCKGLLYLHEKGIAHCDLKTQNILLRYNEKENVCVAKICDFGLSIIKHNTETSGSSIEQYFKNIGTPRYSAPEVLRGELIAASAWFMCDIYSLSLIFFEIIYEEEPFNNLSYAQLQKQVGENGLTPDIPSNVCVDQDISNLMKSCWKFSPVQRPKINEIEKKVNHITRIYCD*KCKSKRIILEYFIVII

>JNK_Hydvu ENA|HAAC01019395_2 (JNK or MAPK8, PTHR24055:SF140), 383 AAs, stress-activated protein kinase JNK-like [Hydra vulgaris]; Sequence ID: ref|XP_002156470.2| Length: 356 Number of Matches: 1 99% identical over 356 AAs ref|XP_002156470.2| seems partial; stress-activated protein kinase JNK-like [Musca domestica] Sequence ID: ref|XP_005191399.1| Length: 380 Number of Matches: 1, 82% similarMFYSVQIGDTIFTILNRYQNLHPIGSGAQGMVCAAYDTVIKQKVAIKKLSRPFQNVTHAKRAFRELKLMKITNHKNIIGLLNVFTPDKSLEDFMDLYLVMELMDASLCQVVQMDLDHERLSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCSLKILDFGLARTAGSAFTMTPYVVTRYYRAPEIILGMGYSENVDVWSIGCIFGEMIRGSVMFPGTDHIDQWNKVTELLSTPPQSFFDRLQPSVRMYCANRPKQKGYTIDELFPEDLFPVGNKQKVNQARDLLLKMLVVDPMKRITITQALNHPYVHVWYDAEEVEAPAPMQYDHKIDEIDHTVEEWKALIYSEVLSYQHEQQQKAKQASCINASLTTRSVETPSKQS

>LRRK2lN_24207 ENA|HAAC01024207.1 TSA (PTHR23257:SF88, LEUCINE-RICH REPEAT KINASE): Hydra vulgaris, contig meta-ga_c01286: 1035, 345, 1380 (+); 100% partially identical to >gi|449673842|ref|XP_002161214.2| PREDICTED: leucine-rich repeat serine/threonine-protein kinase 2-like, partial [Hydra vulgaris] 26/313 -> 345/632; related to Q5S007 (LRRK2_HUMAN), Brain kinase, ParkinsonMKYMFKLIFVEGMTFFLNMEMLHFLGSILNFKDPFYDLKNYIFIDPQWFCQMMARVVTIKEINPYITQGGILSKPDSFKLFPEPCFTQHFLELFFRLLQRFEVLLPISQDEYLVTSKLQSSFPQHLTEAKLSYFEDPNVITRRYDFPHIPIGFWPRLLARILSFPKLTPGAHLEKLNLEMDYWQNGVFLHCSQSFCLVSGDEKNLNILDVQSQRSFVGYQLFVSVIDLIDGIVDEWYPGLNDISQKRIVKRLVPCHNCKLIFLSKNDIRFSFDLNMCIASSYDSDSIKCNECGRFSSISYIAPDAVFADLGNLVVSKWKNKFLDKKYKLGFGAFASVYKVKIDGT

>LRRK2lC_Hydvu ENA|HAAC01010095.1 TSA (PTHR23257:SF88, LEUCINE-RICH REPEAT KINASE): Hydra vulgaris, contig CUFF.11264.1: 1086, 1, 1087 (+); 100% partially identical to >gi|449673842|ref|XP_002161214.2| PREDICTED: leucine-rich repeat serine/threonine-protein kinase 2-like, partial [Hydra vulgaris] 1/644 -> 208/851; related to Q5S007 (LRRK2_HUMAN), Brain kinase, ParkinsonGNCPNRMLRHEVDIIKRLHHPCLISFIGVSIRPRALLLEYSPLGNLADSIASQKISKNKTLKHRIALQIAEGLDFIHKHDIVYRDLKPSNILVFSYSLTVPVNIKLSDYGISQHGTYQGFIANKGTPKYKAPEVEDSEYSTEVDILSYGVTIYELVTNGQRPFRDLSYEKEFKDAVLNNKPIDSLISHGFEPWPDVEDLIKSCLRKNPEERPKAETIVNILINTDFFCLKKHLVICKGFETIDCLTTCTFFDSKIKNVEVWAACGGCGLNSHLSWFSATQTNKQVVQGTMTKIGQILCMISYKHFIIVGTKERRVALYDAQEKCFKHKLAQFSDSILCILHAHGFNLFLFGLADGNIAILNF

>MAP3K7_Hydvu ENA|HAAC01027536_3 (also named TAK1, PTHR23257); 488 AAs, 98% identical to PREDICTED: mitogen-activated protein kinase kinase kinase 7-like [Hydra vulgaris] Sequence ID: ref|XP_002167355.2| Length: 344 Number of Matches: 1, 1/ -> 280/286; 53% identical, 68% similar to PREDICTED: mitogen-activated protein kinase kinase kinase 7 isoform X7 [Gallus gallus] Sequence ID: ref|XP_004940435.1| Length: 489 Number of Matches: 1; Uniprot. O43318 (M3K7_HUMAN) Serine/threonine kinase, which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.FQNNLEHFLLSPSHGFPSSPPRGFINEIDYNELTSFEIIGRGAYGTVQKAIWKNKMVAIKTIENQNDPKEFKDEAKRLSMVQHKNIIQLYGTIINGPKQCLVMELAECGSLYTLLHTPLDTETIHYTFAHVLSWSLQCAEAVEYLHNIKPKPIIHRDLKPLNMLLMKSGTVLKICDFGAACHLHSDMTSNKGTPSWMAPEVFEGSRYGEKCDVYSFGIILWEMLTRKKPFDGIPCQIMWKVMHGVRPAQIKGVPQCFEVLIKRCWEKEEKDRPAFVDIVKFLKKANLYVTGGSLPIMEPAYKQLPWFDXEIQSSVSIKQNNQERNIESSQPITPENISTSSIRTNEHFQLMPPTPPSKFYDPIQSQWNLIPPDLMPICPLEDPRSYHXYENYMEALKKYISIQXNIEFLKQRRDXLKKNIIDLXKEQXKXPCLADFIAAQESRQQLLDMHKTIKPLLENERAKFAKKVFNKSIIFINLFQFIIKKPFD

>MAPKKK2l_Hydvu ENA|HAAC01033260.1 TSA (PTHR24361, MITOGEN-ACTIVATED KINASE KINASE KINASE): Hydra vulgaris, contig miradenovo_c11324; 75% identical, 84% similar to PREDICTED: mitogen-activated protein kinase kinase kinase 2-like [Hydra vulgaris] Sequence ID: ref|XP_002161203.2| Length: 256 Number of Matches: 1; partially identical to PREDICTED: uncharacterized protein LOC101238726, partial [Hydra vulgaris] Sequence ID: ref|XP_004209861.1| Length: 218 Number of Matches: 1; 48% identical, 63% similar to PREDICTED: mitogen-activated protein kinase kinase kinase 2 [Xenopus (Silurana) tropicalis] Sequence ID: ref|XP_002942055.2| Length: 630 Number of Matches: 1MEHKKKMLIVGKKLTEDNIANIKYIFAKNIDSGIEKITTGLEMIEALEQIGFISENNYQGFINILDTLNRTDLISIINGDSEINAANINVSYEELSSEIIDEVAYQIGSEWRRFGRHLNLKDVDLEHIDVDYKKTHDKALQLLKLWKQKSKEGCLTWSQLKKQLELFERFDIIRELKKKFKQLRDDEQVAIAPNDVIDNLNMVEFISDIDNFKLKPIKVLGSCAFGKVYLCIDERTGKKLAMKSIDTGNTDNNANAKKEVEKFKHEISLFQTLKHEQIVKYYGSSSKSTCVSFLMEYMEGGSLYDKVSNKALDEKTASEKSYQILCGLEYLHNKNIVHRDIKCANILLDLYGNCKLADFGISKQIQTIRSHAGCKTSAGTPYWMSPEVISATFLDIEYGKKADIWSFGCTVLEMLTTKPPWSHLDPTPAMFQIVSSPTIPHLPDNSSNSCITFVNDCFQRDPKIRPNALQLLSYDWVKRSA*

>p38a_Hydvu ENA|HAAC01033981 (p38 alpha, PTHR24055); 77% identical, 87% similar to PREDICTED: mitogen-activated protein kinase 14-like [Hydra vulgaris] Sequence ID: ref|XP_002156118.2| Length: 285 Number of Matches: 1; 59% identical, 74% similar to mitogen-activated protein kinase 11 [Gallus gallus]; Sequence ID: ref|NP_001006227.1|Length: 361 Number of Matches: 1; 60% identical, 75% similar to Chain A, The Structure Of P38 Alpha In Complex With A Dihydroquinolinone Sequence ID: pdb|1OVE|A Length: 366 Number of Matches: 1; also related to MAPK14 Q16539 (MK14_HUMAN)MERLPTGFYKEELNRTTWEIPERYQDLNVIGAGAYGQVCSATDTHTGMQVAIKKLSRPFQSVLHAKRAYREILLLQHMCHENVINLLDTFTPQQTIDEFQDVYLVTCLMDRDLKDIIKIQSLTDDHVQFLIYQILRGLKYIHSAGIIHRDLKPGNIGVNENNDLKILDFGLARICEDSMSSYVATRWYRAPEIILNRTQYNSQADIWSVGCIMAELITGRTLFPGDNEIDQITMIMELVGKPNDNFLDKMTSVQARSYIKFMPNYVPQDFNKVFPIATAQARNILQQMLVFDPEKRLSAEQCLQHPYFIHWHDPDDEPTAPFFEKVPELNECTVDAIKLLMLNEIRNFVYKPPX

10



>p38b_Hydvu ENA|HAAC01013825 (p38 beta, no PTHR); 100% identical to PREDICTED: mitogen-activated protein kinase 14-like [Hydra vulgaris] Sequence ID: ref|XP_002156118.2| Length: 285 Number of Matches: 1; 45% identical, 65% similar to mitogen activated protein kinase p38-2 [Homo sapiens] Sequence ID: gb|AAB66313.1| Length: 364 Number of Matches: 1 related to MAPK11 Q15759 (MK11_HUMAN)IFLTDFQDIDQLTKIMQLVGKPTDDFLAKISSANARSYINSMPNYVRQDFDKVFPTATAQAKNILHHMLLLDPEKRFSAEQCLQHPYFSVYHDPDDEPTAPLFEEGAELNECSIDTIKALMLNEIKNFVYKPPPEEVME

KINASES: Tyrosine Kinase Non-receptor protein (TNK)>ACK1_Hydvu ENA|HAAC01013431.1 TSA (PTHR24418, TYROSINE-PROTEIN KINASE): Hydra vulgaris, contig CUFF.18479.1: 474, 3, 477 (+); identical to T2MED2 (T2MED2_HYDVU); Activated Cdc42 kinase 1 like, Tyrosine kinase; Q07912 (ACK1_HUMAN, 1038 AA) Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42, which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and ARAPECLNFGKFSHASDLWSFGVTVYEMFSLGAQPWSGLNGSEILHKIDEPNFERLKKPSYCPSTLYSIINNTCWKHIPEERGTFSTLEKELLNVLPYEVTAISARVSEMSHQLCYSQGDIITIFESNSNSFMWKGQNRRTGAVGFFPSEYANLKLGTIS

Leucine-rich Repeat Containing proteins (LRRC or LRC)>LRRC1l_38451 ENA|HAAC01038451.1 TSA (no PTHR): Hydra vulgaris, contig miradenovo_c43753 : Location:1..488, Frame shifts, 91% identical to LRRC1_Hydvu gi|526117778|ref|NP_001267856.1| leucine-rich repeat 1 [Hydra vulgaris] >gi|91177616|gb|ABE26985.1| leucine-rich repeat 1 [Hydra vulgaris]QSNLKKKLACVKGNERREKISSKKALKEEDLTVIKQVDKKIEDPKEHKANISSARFVWLISFIAFAIIVLLFLFKTDFCKVHVIQYVNRWSKVLVGSSKNII-

>LRRC2_Hydvu ENA|HAAC01022673_3 (HyLRR-2 or LRR-Slit, PTHR24373:SF110) 485 AAs, 3x Leu-rich repeats (N-term), 3x EGF repeats (C-term),

deltablast: leucine-rich repeat 2 precursor [Hydra vulgaris] Sequence ID: ref|NP_001267851.1|Length: 485 Number of Matches: 1: 99%; 2nd besthit: slit, isoform F [Droso mel] Sequence ID: ref|NP_001261017.1|Length: 2157Number of Matches: 12, 40% similar, 2e-66MRLIQLTILQFVYIAFGDSCPSKCLCTNNGEISCTKQNLTSKDIEMMLFPINATMLNLTENLLTYLPTNIFNNFTKLKTIDLRRNLLDYLPSNLSLEIPSLNVIYLNNNKLREIKESSFDGYDKIITLDLSGNLLENIPPSVFKKCADLLHLNLRANQIDKINDQSFATLEKLRTLSLSENKISFIPPGSFNSLKSIEVIKLDANKLEMIAEGLFSTHLIELHLASNKIVQVLPKAFHNQDFKILDLSDNYITTLSMDSFVDVYYESLVLDGNPIICDCRLNLLVDQYHRITGSCQLPSALKGLSLSNVLSHNFLNCTICSIXPCQNEGKCIIQSEGDKYSCVCEPIYTGKNCETKKKLCELNPCLNNATCSDVNSTKGYICNCTFNYKGQNCKDLKVCLSNPCHNNGICIENVSHEKHRCKCQRGFEGTFCQKRAKKFPPGWIALIIVSVVVLVIIGSVLYFCKFRRQKTVISEESPLNVKPVM

>LRRC28l_31497 ENA|HAAC01031497.1 TSA (PTHR23155, LEUCINE-RICH REPEAT-CONTAINING PROTEIN): Hydra vulgaris, contig miradenovo_c02481; 98% identical to PREDICTED: uncharacterized protein LOC100214715 [Hydra vulgaris] Sequence ID: ref|XP_002166466.2| Length: 486; 25% identical, 42% similar (176/122 -> 352/310) to PREDICTED: leucine-rich repeat-containing protein 28 isoform X1 [Bos taurus] Sequence ID: ref|XP_005221813.1|Length: 315MESFSDFGEQHLKVKEVFLKEFSKLILESGVIKQELGKSTLNKCFGEKYDNHNLTQFFVKWIIKEIEGSEQKRKSVQEINKVMLIVESEQDVLRVHAMSCDIKFFFYQENSVCCIKKKLFKKETVNKWGWPNRWFVDVRLFKETIKSCISSIWYLPQVERLEMVECSLGKNIYEKLSFVPYDIGYMKHLKVLNLRHNDLKRLPFALTMCEKLEELLIEYNSFTCLPEFILQFPCINKLYRFHNRFDFSNFNFIEEIPYNKLVFNCETLYLMSLKSILRQVNNYDLKDFLQSFPVHLHHDALKLINGICSNCHKFILHEESYFMYIYKYQTFVNCSYVPVAVYTCSRVCAEVSLNQKKVYDRDDETAETISFSCFDSETKSNSSCFNSKLRSIKRFICL

>LRRC40_01897 ENA|HAAC01001897.1 TSA (PTHR23155:SF405, SUBFAMILY NOT NAMED): Hydra vulgaris, contig asmbl_17728_ext ; 100% identical to >LRRC40_Hydvu gi|221117516|ref|XP_002157758.1| PREDICTED: leucine-rich repeat-containing protein 40-like [Hydra vulgaris]MNNNSRLNKNRFKPLPEQSEEKKVGVPTSLLKSARHTGQLNLSGRSLKEVPLDVWRINLDIPSQTISLGEVDERWWDQVDLKKLILASNEIKCIPNEVKYLPALNVLDAHDNCIEYLSDEISELKELGKLHLSHNKLTSLPDSLCQATALKVLLLAGNSLQSLPVNFGFLINLEELDLSDNKLTSLPESFGSLVQIKKLDLSKNLLTSLPNSFDSLKSLINLNLSTNKLTVLPKGFGKLTSLEIFECSYNLITTFTTFDDQTNIKQLFLGYNRIQKIEDNAFEKMQSLVSLSLRDNAISEIPESFTKLRTLERADLSNNSLSTLPNAVGKMNLKSLTLDGNSMRSIRRDIVDRGTNAILAYLKSRLPEEKVPDEEIKIPKSVSKVNDNDQQKKIQENNKAVTDQFLIATTKNLSFSGGSGSIPSSFWLPGAQISKISIQHNGLTVYPLEIMNYASTLSELDISHNKLSNILDTVNILTKLVFLDLSHNVLSSLPSSISQLEHLLEVVLSFNKYSSIPPCLFKCKKLQTLLLSNNQITDIDVVGLLEMKCLRTLDLSNNNIACVPPQLGNVEWLQSLNLDGNPFRNPRAQILMKGTQNLLAYLRDRIPT

>LRRC59_Hydvu ENA|HAAC01038433_3, 274 AAs, leucine-rich repeat 1 [Hydra vulgaris] (PTHR23155, LEUCINE-RICH REPEAT-CONTAINING PROTEIN): Sequence ID: ref|NP_001267856.1|Length: 273 Number of Matches: 1, 100%; leucine-rich repeat-containing protein 59-like [Macaca mulatta], Sequence ID: ref|XP_001093756.2| Length: 239 Number of Matches: 1, 1e-50, 66% similar; Human LRC59: Required for nuclear import of FGF1, but not that of FGF2. MAEENKWTKEKIKSKIIDNELDLSLCSITRIPVKHLISFTKVTVLDLSCNKINIIPDNFTSLTHLVQLDLSKNSLSELPEDFGKLFKLKKLDLLNNNISNLPLSFGKLKNLVWLDLKGNPIQEFLPEVVGDCLKPVECQTCAKSVVEYYENLQFNKEQNELKKKRKEEERLAKQLKEEASLRQRKREERKNKQQKALKEEDLTVIKQVDKKIEDPKEHKANISSARFVWLISFIAFAIIVLLFLFKTDFCKVHVIQYVNRWSKVLVGSSKNII

11



PHOSPHATASES: Tyrosine phosphatases>DUSP22_Hydvu ENA|HAAC01039539.1 TSA: Hydra vulgaris, contig miradenovo_rep_c48272 : Location:1..640 (no PTHR); 100% identical (1/1 -> 176/176) to PREDICTED: dual specificity protein phosphatase 22-like [Hydra vulgaris] Sequence ID: ref|XP_004208355.1|Length: 176 Number of Matches: 1; 43% identical, 60% similar (1/1 -> 174/171) dual specificity protein phosphatase 22 isoform b [Homo sapiens] Sequence ID: ref|NP_064570.1| Length: 184 Number of Matches: 1; Q9NRW4 (DUS22_HUMAN) Activates the Jnk signaling pathway. Dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). Myristoylation regulates subcellular location, and is necessary for activation of JNK. MGNGMNKVLPGLFIGSLEDSQDENQIKSNNITHILSLLDEPPELKPFLQNLKYKSIIIQNLPGQNMMQYFHECIAFIHRGRLSEGNVLVHCDTGSSRASTVCIAYIMTIADVDPRSALRYLKAMRNIVRPNHGFRIQLVLYHRMEISEVRDALIEVFGDINPADGAEIKKVLAGLS

>DUSP2Ab_Hydvu ENA|HAAC01005102.1 TSA: Hydra vulgaris, contig asmbl_31090_ext (PTHR11871) identical to PREDICTED: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform-like [Hydra vulgaris]; Sequence ID: ref|XP_002170565.2| Length: 453 Number of Matches: 1; 72% identical, 86% similar to PREDICTED: protein phosphatase PP2A 55 kDa regulatory subunit-like isoform X2 [Musca domestica] Sequence ID: ref|XP_005179637.1| Length: 443 Number of Matches: 1MVVFVNMSSGSDDGPVKWSFSQVKGTSEEEITEADIISTVEFNHDGELLATGDKGGRIVIFQKDNAPKSSPRYGEYNVYSTFQSHEPEFDYLKSLDIDEKINRIRWLKRRNRAHFLLSTNDKTVKLWKISERNMRIDGPLNTKTLDGTQELTAGEIQKLRIPELQPTPLMVEASPRKIYSNAHTYHVNSISINSDDETYLSADDLRINLWNLQRTDQSFNIVDIKPANMEELTEVITSAEFHPDSCNIFVYSSSKGTARLCDMRDSALCDKYSKLFEEPEDPSNRSFFSELISSIADVKFSHNGRYMLTRDYLTVKVWDLQMERKPVETYQVHEYLRSKLCALYENDCIFDKYECCWSGDDTSIMTGSYNNFFRIFNREQKSGVCLEATRENMRPKQLLKAKKITTTGKRKKEEISVECLDFSRKILHMAWHPNDNIIALAATNNLYLFQEKV

PROTEASES: Mannan-binding lectin serine protease (MASP, complement activation)>LCFCl_Hydvu Trypsin ETA-Mannan Binding Lectin ENA|HAAC01038788.1 (PTHR24265:SF76, TRYPSIN ETA); from residue 68: 99% identical to >LCFCl_Hydvu gi|449691174|ref|XP_002169768.2| PREDICTED: limulus clotting factor C-like, partial [Hydra vulgaris]; Uniprot P28175 (LFC_TACTR). This enzyme is closely associated with an endotoxin-sensitive hemolymph coagulation system which may play important roles in both hemostasis and host defense mechanisms. Its active form catalyzes the activation of factor B; from residue 108: 99% identical to >MASP1l_Hydvu gi|221117933| ref|XP_002161810.1| PREDICTED: mannan-binding lectin serine protease 1-like, partial [Hydra vulgaris]GYITDPSGITPYYYGHKLNVHCDTFHDLFGSKTITCVGNNTWAGLGSYCVKTCGKSVQRNFELETCKGGVHRVASIQYTHPWLVAIKEGDKLKCSGILISKEWILTASHCVAYAPERNGDPGNLIVLLGVTDWNLLGKSSQIRTVKEIRVSQKFDYGIHSDVALVRLSSEVVMSGDIQPICLPSDKTHRHLFRAKKKVVSIGWQHERIQKKTDRCLEIEPKTTCKQHYDKLHIDLHTNRYKTSDGREKLMPADLICVKELPQGNSDLCKIMPGSGLVAYHEESKKWYLGGILTWSSDKLHDCRETMTTFSIYSQVHRYVLWIQSRTKLNLNYPDTDYVPQEIKS

>MASP2l_Hydvu Mannan Binding Lectin ENA|HAAC01018424.1 (PTHR24255:SF4, SUBFAMILY NOT NAMED); from residue 46, 100% identical to MASP2l_Hydvu gi|449686570|ref|XP_002154755.2| PREDICTED: mannan-binding lectin serine protease 2-like, partial [Hydra vulgaris]. MASP on UNIPROT: Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties, which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5.MHYSTSTLFFTILQVVKNVEIKDNTKCGGNLQKLVGTFHTPNYPKMYPNKLNCIWNITVPNGYRLQLNFTEFELEWTDHCSYDYVEVKATNGTIGKYCGKRTEKPLAYVTAPSKEPIYSVDNSLEVLLYTDFSNEIEVFGFIAHFAALDINECLLNNGDCSQHCHNYIGGYYCSCRVGYFLHDNNHDCIVSCQNVIQNKMEGIITSPEYPYPYPPFARCEYHITAEKGYFINLRFLDFKIEDHHESLCPYDYLLIEDEKEKKGPYCGKTKPDNFISFSNWLIVEFRSDKSLALTGFKAEFKLQ

>MASP2_Hydvu Mannan Binding Lectin ENA|HAAC01022976.1 (PTHR24255:SF4, SUBFAMILY NOT NAMED); from 1 to 64: 100% identical to PREDICTED: MASP2l_Hydvu, mannan-binding lectin serine protease 2-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002154755.2|IEDHHESLCPYDYLLIEDEKEKKGPYCGKTKPDNFISFSNWLIVEFRSDKSLALTGFKAEFKLQAIKCPTLTPVANGFMSGHSNFSLKETVTFSCREGYIYTGSETRTCLPDGSWSGYLGNCTRITCNDPEIIPDEGYITDPSG

PROTEASES: Cystein-type endopeptidase (Caspases)>CASP2l_Hydvu ENA|HAAC01010254|HAAC01010254.1 TSA: Hydra vulgaris, contig CUFF.11586.2 (no PTHR); 100% identical (1/1 -> 402/402) caspase-2-like [Hydra vulgaris] Sequence ID: ref|NP_001274285.1| Length: 402 Number of Matches: 1; 28% identical, 43% similar to caspase 9, apoptosis-related cysteine protease [Danio rerio] Sequence ID: ref|NP_001007405.2| Length: 436 Number of Matches: 1MDKSHKIFLLKNRLEFVKDLEPNDVTGFLYQEHVISENDKDVIDNLKTRRDRVEFLMDLLPRKGPKVLPKFYNILNMLPSYKHLAQLIAKQVNFESANLDIIDGKQEEVAVRPRSSSQLLSSMLDSYSMTSTSRGWCFILNNVNFSYMSSRRGSERDAENLKLLFEKLGFKIWVVNDADAASFSEKFTELAKKPDHGCCLIVCLLSHGVAGKIYGTDGELVAVSELLEILSEGTEKVKSIPKLFLIQACRVVEKLDAIDSGLSPSKKFTLPKSGMTEVVSIRSDRFVSIRSDIPFDRSQTQKTYSMDSLTSFINEHEKPLQSDILLGYSTFPGDVSWRHTKNGSYFIDSVVSVFSNYAATEDVASMMVKVNQLVKEKLAKNGEFQIPAPVITLTKKLFLFPI

>CASP2_Hydvu ENA|HAAC01011771.1 TSA: Hydra vulgaris, contig CUFF.14840.1 (no PTHR); 99% identical to CARD caspase 2 [Hydra vulgaris] Sequence ID: gb|ACY95436.1| Length: 476. 100% identical to E2DGP9 (E2DGP9_HYDVU); related to P55214 (CASP7_MESAU) Mesocricetus auratus (Golden hamster). Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Asp-Glu-Val-Asp-|-. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit. Interacts with BIRC6/bruce. Cleavages by granzyme B or caspase-10 generate the two active subunits. Propeptide domains can also be cleaved efficiently by caspase-3. Active heterodimers between the small subunit of caspase-7 and the large subunit of caspase-3, and vice versa, also occur.MEAIHREILRKNRMSLSHSNMNTEEVCTCLIRDNVFTINDKYSVESYSSPVKKIEKLLDILSHKGANAFSTFTKVLNELKLFHLSKLISTDKNANITNQSRQSEEINVSNDDLEYSSCKHARLQEESLKEEKESDVSNGVQTKPQDKSLKQEKESEVSDSYDALDGPINKPDVKEDNHGIDNEEDGRMAFLSNIRSAPKFSNPNDFVAPVENIQHNLEECYAMNTNPRGLFILVNNKKFLPSSGMHEYTRNGTDEDAKCMKELFEELGYVIESYQNISVYEMRKIFKKASLISYSGYSALAVCILSHGQEGVVYGIDGTIDIKEITGFFRGSNLMGKPKMFFFQACQGSDYMDGVEPDTGRMETDGPPEYGNEISLPTEADFIYAYSTVPGFYSWRNSAKGSWFIQALVEVFRKHAHKMDVVRMLTRVNRIVATKKSQTGQLSSHNKRQISSIVSQLRKDLFLCPPNGPLRSLDFV

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http://www.uniprot.org/uniprot/P48740#P48740-2


>Casp7l_Hydvu ENA|HAAC01039737 (HyDD Caspase, no PTHR); 40% identical, 59% similar to caspase 7 [Hydra vulgaris] Sequence ID: ref|

NP_001267753.1| Length: 407 Number of Matches: 1 (score 857); 39% identical, 56% similar to DD caspase [Hydra vulgaris] Sequence ID: gb|ACY95434.1| Length: 393 Number of Matches: 1; 28% identical, 46% similar to PREDICTED: caspase-7-like [Danio rerio] Sequence ID: ref|XP_002667104.1| Length: 266 Number of Matches: 1MSNNVNNCCQHGNNVQVTLTSEVLDEIASLIGSDWYSFGCKCGLERSVLDNIEHDKKTVRDKAFSVLSKWIDINGDVGWNDLKICLKKSQKNNIVVAIELKFSENLMNIQPSTNQVVSSETKKEVYPMKRQTLGILHIFNNLHRDDDKVHQRAAQNDVKTLKKTFTEIKFDVNVHMPQNFDEMYTSLNNVLTDQYKEYNIFAIFFIAHGREGELFGPDKNNTISSLTLKKWLNDNPSLKDIPKLVFFDSCRGDEKDIQEINSTVPAARSIKANFSDFFWCCSTVQSYEALSMPGTISYSPYVRELCKQILEKHMTTNFEKIYKEIQKYMSENPITIDGNFYRFQMPDVQSNTLTKKLFLNMGQRINNPVNNGAQQ-

>CASP8l_Hydvu ENA|HAAC01010402.1 TSA: Hydra vulgaris, contig CUFF.11856.1 (no PTHR); 100% identical to PREDICTED: caspase-8 [Hydra vulgaris] Sequence ID: ref|XP_004207819.1| Length: 473 Number of Matches: 1 (1/155 -> 319/473); 34% identical 55% similar to caspase-8 [Gallus gallus] Sequence ID: ref|NP_989923.1| Length: 482 Number of Matches: 1MEEKSKALTSVNEISQKSGSTFSSTFNSTFNSAQTSASVSASTSVLNLDSIKKEYFVENTSIELGIYSMHNVPSGICIIFSNYFDKEVIITDENKKLEQRLGNGADESQLKETFTWLNFDVLVYKNKSSKDIVQLLYSNLKNSSIQDCFVCCILSHGYRNGIYGSDGSRLSFEELWTTVEDASSESLQGKPKLFFIQACQTEINVKEMSLSDIGIKVDFEDVLTSLATLPGKVAFRDVTRGSWYIQTLCETLKNRAYDSSLLDILTELNSNMASKVDYYKVCSEYKIATQMSSIQSCTLSKKLFFKPYDVTALSRLRIL

PROTEASES: Calcium-dependent cysteine-type endopeptidase>Calpain15_Hydvu ENA|HAAC01032244.1 TSA (PTHR10183:SF279, CALPAIN-15): Hydra vulgaris, contig miradenovo_c06185: 1503, 1, 1504 (+); T2MI17 (T2MI17_HYDVU) 100% identical to PREDICTED: calpain-15-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002163326.2| Length: 578; 53% identical / 67% similar (56/552 -> 501/1002) to PREDICTED: LOW QUALITY PROTEIN: calpain-15-like [Saccoglossus kowalevskii] Sequence ID: ref|XP_006817792.1|Length: 1175FKLFSEISQQQNDSTDNTLQSKNNTPENNFLLNCSCNNEELNTDNSTDKCYKYLHRQRSLKSDQIRGKHEELAIEKWKDIVLFCKQAQIQFVDDSFPPSAKSLTFSSLPYDKVTYWLRPKEIFRSNTQTKWTMFRNPRPSDILQGTIGNCWFLSALAVVCERPELLEKIMVTREICDEGAYQIRICKNGKWIVVLVDDLLPCDANGQLVFSQAARNQLWVPIIEKAVAKSVGCYEALVAGRCIEGLQLLTGCPCECILLSNHMDDAEEDIVDKDLVWAKLLSSRNAGYLMGASCGGDITNQEAIDAYTKVGLHAQHAYSVLDIQQFGDNRLIRLRNPWGRGSWTGRWSDSSFLWTNELREMLNAHGSEEGVFWISLEDMIKYFDSVDVCKYRPDWTEVSIEGRFPSPNNNFGQACHVTVFNPTEIDITLFQESNRGSQKSSLATLDLLIGVYKATSGSSQPKPLKYITHSERKIKPSVLCNVFLDVGVYLIIPAAFNHWNS

PROTEASES: Matrix Metalloproteinases (MMPs)>HMP1_Hydvu ENA|HAAC01033022.1 TSA (PTHR10127, DISCOIDIN, CUB, EGF, LAMININ , AND ZINC METALLOPROTEASE DOMAIN CONTAINING): (HMP1), 336 AAs, zinc metalloproteinase nas-15-like [Hydra vulgaris] Sequence ID: ref|XP_004209002.1|Length: 285 Number of Matches: 1: 1/1 -> 288/284 98%;MNIFWAFLVLLQAYISAGQGQVRVNYGNPDAFEGDIGLDPETRAIINGQLTENQFKGVTLDRIWPGAQIPYVFDNNFDNRRRQLVNQAITSYNQHTCVRFVPRTNQRDFVHMVNEQGCWSIIGRQGNSQKLKLGDWCLDIGTAIHEMMHAAGFYHEQSRNDRDDHVVIFWNNIQRGEDYNFQKYRTEYYGQTYDHNSIMHYRNDEFSANGKNTIQAKNNPGLKLGNNQFSKSDIAAINQMYKCSGVTGITPAPCEDSHSNCAAWAKANECNKNPNWMRPNCKKSCGTCSLKNKLLKLNVDKTKNETKSRIIFFFFKCLLRKIKKIFFLGANLKTI

>MEP1B_Hydvu ENA|HAAC01042634.3 TSA (no PTHR) (also named HMP2) metalloproteinase 2 [Hydra vulgaris] T2MD62 (T2MD62_HYDVU, gene name MEP1B) gb|AAD33860.1|AF140020_1 Length: 496 Number of Matches: 1 98%; meprin A subunit beta-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002165576.2| Length: 407 Number of Matches: 1 99% similar KKTLHLNNQEKKIVAQILFKKNLEMTKLVLFLLSIALCHSFPEEENNDPEGVLFGGDILLTPEQKSIIEVSGDISQAGLLKALRQKRAALSNSSILWLPNNKVVPWSITKQLENTAEATFGLMAAFREWEERSCLTFKRRTDEKDYIEFFQGSGCWSYLGRVGGLQNISLDDGCWGKGTIVHEIGHAMGFGHEQNRPDRDQYITIRWENIPESKKHNFRLYSNSLVDSLNSPYDYRSYMQYSKTAFGINDSVTLDPKLPGIFQLGQRVGFTEHDQYQAMQLYRCQGKTTRPTTFFPRYDLKGDYTCDFETDLCGFTHDKTATFEWAQIYGETPSRGTGPDSDHTTGRLGTYVYIEASYPQKKNDKARLKTKWFEKPLSAQCFSVFYNMFSRNASMVGEFNIYIDDTVTIKNIFSQSKSEPNNDWKNLLINIKPEGPYQVIFEGIIGNGWQGDIAIDDISISAGNCPTNIEISDNFSNDSNSCEDINDREAEYCRQWEQAGYCVSEEKTLKLYCRKSVIFAKCLGFKKAYWLCX

>MMP2l_Hydvu ENA|HAAC01027698.3 TSA (no PTHR) 363 AAs (72 kDa Type IV collagenase like); from 68 -> 363 identical to >gi|449691922| ref|XP_002163948.2| PREDICTED: 72 kDa type IV collagenase-like [Hydra vulgaris] Sequence ID: ref|XP_002163948.2|Length: 296 Number of Matches: 1: 68/1 -> 363/296 (similar to MMP-27); Sequence ID: ref|XP_002164557.2|; P08253 (MMP2_HUMAN): 72 kDa type IV collagenase EC=3.4.24.24 Alternative name(s): 72 kDa gelatinase Gelatinase A Matrix metalloproteinase-2, Short name=MMP-2 TBE-1 MASLLRVRFGTSNVIGRRTASAVAHAIAPDTRYCPANPASLERTGVVSEALLAKEKGPWNKLSKEDKMAFLSLILFGFFSLGACLDNPTTFLKRYGYLQSGYNDNNSLTSAIKKMQKFGNLPETGVLDKQTLKLMSTPRCGVSDHNYLGYSSSKWSKNVLTYKIINHTPDLGPAETARIXQEAFNKWSQVTPLIFTRGYGATDMTVDFGNLRHSSCGYDFDGPGGVLAHAFFPTDGRTHFDEDEHFTDKTTAGTNLLWVAAHEFGHALGLEHSTVQGSLMYPYYQGYKEPFVLHQNDISRIQQLYGGSGGATMPPTPITTLSPGACTNFYGDSHCDSIKYGCAWDHWKDYMRTNCYKTCFCKV*

>MMP7_Hydvu ENA|HAAC01029785.2 TSA (no PTHR) (Hatching-enzyme like), full length include a C-moiety identical to ENA|HAAC01005650; Sequence ID: ref|XP_002163814.2|Length: 309 Number of Matches: 1: 1/1 -> 306/309, 94%; 50 kDa hatching enzyme-like [Hydra vulgaris] Sequence ID: ref|XP_002165203.2|Length: 270 Number of Matches: 1: 1/1 -> 306/270; Deltablast: 3 domains: PG-binding domain / ZnMc MMP / ShK superfamily; 1st vertebrate hit: matrilysin precursor [Gallus gallus] Sequence ID: ref|NP_001006278.1|Length: 263 Number of Matches: 1: 54% similar, 5e-89 MMLKVFAFECLFVAIVICKADIDAEDFLTSFGYLNRNAFNGVSVTDAIKDYQSFNNLKVTGVVDANTKAEMAKPRCGNPDRHGYNGYSKWTKTTLTYSFRNKCEDLSDGAVRQTIREAFKVWSDVTHLAFTETSGKGDITIGFHHNSHGDNSPFDGPGRVLAHAYFPPEGRLCFDEGERWVIKTTGTDLFEIAIHEIGHILGLEHSNIQGTIMYPSYSGYRPNLQLHYDDRRRIQQMYGIKTGTSTGTGTGTGTGTGTGTGTGTGTGTGSCTDKVIDCSKNLAYCRSPPQWHEYMKVSCAKSCRFC

>MMP17l_Hydvu ENA|HAAC01031712.1 TSA (no PTHR) (MMP-17-like): from 42-126 AAs: matrix metalloproteinase-17-like [Hydra vulgaris]

Sequence ID: ref|XP_004205998.1|Length: 133 Number of Matches: 1; from 124 to 203 AAs: stromelysin-2-like [Hydra vulgaris] Sequence ID: ref|XP_004205999.1|Length: 206 Number of Matches: 1 INPETRRFILNPRCGVSDKFIGMNSMRKHNYLIQNTTWTNSTITWFLDGRNSAGILPTEVREIMQKSFQKWADVTNLNFIEVSNSDSADICISFQKSLHNVGHLDQDFSQDRYAHAFYPRTNQEPLDGDCHFNDDKKFSTGNYSVAHSSGKISLFLIAIHEIGHSLGLDHSHIQGTIMYDHYEHMHHVEDLTPYDIDGIQKLYGRKVLPVTNDSIMATTVRPKVVCPTTVDASVQISEGNIKKTLVFNKENYYVLNSDDFGIAEGPFSVSSKFAGVPYVDAVFTRGDKFHFFFTAIVILYLRTIHWT

13



>MMP18l_Hydvu ENA|HAAC01015927.1 TSA (no PTHR) (MMP-18-like); identical to matrix metalloproteinase-18-like [Hydra vulgaris] Sequence ID: ref|XP_004209646.1|Length: 251 Number of Matches: 1 MLMIFFHMIVYFIKTHGELNQLKNHHIIYLQNNGYLPKYGNKSSGKGFKNFELLNALKKFQEFAGLPTTGVLDLITVKKFNQPRCGMEDKFSNLRPKRYVTQGGKWHKKLLTFQILNYSNDLSKNQIDKTIKDAFHKWEAVSRLKFTERSNGIADIKIKFTRSNHGDPYPFDGPGGTLAHAFYPGTHDLSGDIHFDDDELFTLNTMEGKDLSWVVLHELGHSLGLEHSHEKGAIMYPWYERHDGREIVLHEDDIEGIQFLYGIPDNEKHSHDKNQPSRCVEKIDAVTIDQRGYVTVISKGFVYTFDNKLDLSEQPVSLHAKFNNIKEIDASFTKINGHIIYIHADX

>MMP24_Hydvu ENA|HAAC01039124.2 TSA (no PTHR) (MMP) 485 AAs; matrix metalloproteinase [Hydra vulgaris] Sequence ID: gb|AAD45804.1|

AF162688_1 Length: 484; PREDICTED: matrix metalloproteinase-24-like [Hydra vulgaris] Sequence ID: ref|XP_004211314.1|Length: 484 MFISLGFNLFFIFYVAQSLPVEHIQVPRKTLDYLANLGYYTLSTEVGSINNEKEIRNSIENLQRFAGIPVSGILDAPTQELIETPRCGLPDFKKPNESRNRRYTLQGTTWKKNELTWKLLNNNNDGLTRGEIETTLHKAFSMWEAVTNLKFRQLQINENKKADIEIKFAQGYHDDPYSFDGFGGTLAHAFYPHTNEGLSGDVHFDDAEKFTIESPEGRSLLWVAVHEIGHSIGLEHSNVKEALMFPWYRVQDVRNIQLSDDDVLGIQSIYGSKKSIMLPSTVTPTKKMKNSFQMKAVILDKSTGVTYAFNDDEFYKINNDLKQTEGPFTVSSLFPEVNSVNSGYMDSDGKLIFFKGTRYYTYKNFSDRKLLESGSIFDKYKGIKSGVKTIDAAFVWNNGRTYVFIEDEYYRFGGTKNVLDAGFPRKIVDNWTGVPKNIDSVFVWRNGVTYFFKGSLFYRVNEKGQVLLNYPKSISGAWLNFPNK

>MMP25_Hydvu ENA|HAAC01043328.1 TSA (no PTHR) 494 AAs (MMP-25-like) matrix metalloproteinase-25-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002170324.1|Length: 464 Number of Matches: 1 ; 2 similar seq: MMP25l1_Hydvu ENA|HAAC01029673, MMP25l2_Hydvu ENA|HAAC01026564 MLSDKEELLFLFLSIAAVSYGDFPENALDYLSDFGYYKRNNKDLGSMSGKKEVQNSVESFQRFLGLPVTGVIDKTTQEVMKKPRCGLKDILDDKATRKRRFTLQGSKWSKNKVTWKLLNDNNDGLSRKEVETILENAFSKWEAVADLTFYKLSFTSKEPADIDVKFVQGDHGDPYPFQPWHKIYAHAFYPFNNQGSSGDVHFNDKFNFNVKEKSGVSLLWIAIHEIGHSLGLHHSSVQSSFMYPTYQGNKDQNIHLHDDDILGIQSLYGSKRKPILPSKNTVGTNNTQVTQNKTHLMTSKKHIKVQAIIYDQLTGITYVFNENKYYKLSKSLHETHGPFNVSKLLTKITYVNGGFMNREKKLVFFQGTKYYMFESFTNTKFIKSGSIFDLFKGIKNNVEKIDGAFVAGDGTTYLFTGNEYYEYSSKQKTIESSPKKIAEYWKVPTNIDSVFVWGNGGIYFFKDLHFYRVHQNGGLMKGYPKSIDDIWLKAPKNV

>MMP27l_Hydvu ENA|HAAC01028017.1 TSA (no PTHR) (MMP-27-like) 320 AAs; identical to matrix metalloproteinase-27-like [Hydra vulgaris] Sequence ID: ref|XP_002164557.2|Length: 298 Number of Matches: 1 TYIFLQNKSCDLCSFKKICFFKMTFLMLTLLGFFTLCCALDDPVDFLKRYGYLQTGYSNPNSLTEAIKKMQKFANLPETGVLDKPTLNLMSTPRCGISDQDHSGYSSSKWSKTKLTYKIINHTPDLGLAETARIMQEAFNKWSQVTPLTFTRAQGTTDLVIDFANLRHSSCSWDFDGPGGVLAHAFYPPDGRAHFDDDEHFTDKKSTGTNLLWVAAHEFGHAIGLTHSSVQGSLMFPYYQGYQDPFVLHENDISRIQQLYGGRGGATIPPPKTTLSPVCTNFYGDEYCKGIAYGCAYDHWKDFMSTNCYKTCFCKNLKKT

>NAS15a_Hydvu ENA|HAAC01043407.2 TSA (PTHR10127, DISCOIDIN, CUB, EGF, LAMININ , AND ZINC METALLOPROTEASE DOMAIN CONTAINING): (Farm1) zinc metalloproteinase nas-15-like [Hydra vulgaris] Sequence ID: ref|XP_002159980.2| Length: 336, also named “Astacin 15”; NAS15b identical to ENA|HAAC01028474_2 Uniprot: SECRETED glycoprotein that belongs to the peptidase M12A family. Contains a ShKT domain. Hydrolysis of peptide bonds in substrates containing five or more amino acids, preferentially with Ala in P1', and Pro in P2'. Binds 1 zinc ion per subunit. Highly conserved KTKTLKQKKIKMMKFLVLLLCFVSHVTLSWVPEMENKNLFEGDMVLTPDDINSNGYASIVGGRWPNNIVPYELSRMSSSNHIHVLRAIDEYHKHTCLKFVKRTNQDAYLSFYPGGGCSSLVGYVRGRINDVSLAGGCLRLGTVMHEIGHSIGLYHEQSRPDRDDHVTIIWNNIQSNMRFNFDKFDRNKINSLGFPYDYESMMHYDQTAFGGGQVTIRTKDPSKQKLIGNRQGFSEIDKQQINAMYNCNRGGSTLPPSVPPTVSPVAQCVEGQDLDNRCLGWATSGYCTATDPAHLETMKKKCCKSCKESAICNDKNTRCDEWAKKGECKANPNWMLGNCSKSCLVCK

PROTEASES: Membrane Metalloproteinases >ECE1_Hydvu ENA|HAAC01020813.1 TSA (no PTHR) (ECE) 597 AAs (174 AA missing in N-term) endothelin converting enzyme [Hydra vulgaris] Sequence ID: gb|AAD46624.1|AF162671_1 Length: 770 Number of Matches: 1. Uniprot: Endothelin-converting enzyme-1 is involved in the proteolytic processing of endothelin-1 (EDN1), -2 (EDN2), and -3 (EDN3) to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Cell membrane; Single-pass type II membrane protein. Belongs to the peptidase M13 family “endothelin converting enzyme & immune” on Pubmed: 6 papers! identical to ENA|HAAC01023740AAVFYKSCTNTKLIEQIGDLPMKKLVKDMGSWPVTDESFDESKWDSLEALTTVHKNISIAPVLQVYVAADIKNSSQNIIVF2978529785DQSGISLAKESYLKNSTFHIRHREAYLKYMKSIAKQMGANETGLKYMNDVMEFETQLANITMSVLDRRNYHSIYESMTLEEFSNRTEIPLSWLLRFVNNIFKENNLLVLPSERIVSFSTQFIGKAYKLFNELPKKTQSSYIIWQAVNVMAPLVLGKYQEIFDEYQLEAYSLTDRPPRWEVCISSTLRYFGYALGRPFVEKVYDKTAKTMSTEIIQAIKQVFIDNLETMDWMDAKTKAYAKKKAERIIENIGYPSFILNNTALELEYHGLSIKEDEHFNNYMECRKYDNLKNYFKRGKPVDKSEWSILPTTVNAYYAPTENKIGFPAGILQWPYYDKRAPRAVSYGAIGMVVGHEISHGFDDQGKDFTVEGNFDTWWTKESTDAFKSRSQCFSEQYSKFEMFDRHMNGKQTLGEDLADNGGLRQSLQAYQLWKEQHNEEQKLPGLNLTSEQLYFLAFAQVWCTNYRESSAINQIESGVHSLSRFRVIGTLQNNQEFSKAYKCPEGSIMNPKKKCRVW

PROTEASES: S1 peptidase>Tsp-Trypsin_Hydvu ENA|HAAC01023959.1 TSA (PTHR19897, COILED-COIL DOMAIN-CONTAINING PROTEIN): Hydra vulgaris, contig meta-ga_c00666: 2460, 3, 2463 (+); Novel Hydra protein with 2x LRR8 domains at the N-terminus, 6x Tsp1 repeats from 231 up to 621, and one trypsin protease domain at the C-terminus; besthit hemicentin: restricted to the Tsp1 repeats from position 231, hemicentin-1 precursor [Homo sapiens] Sequence ID: ref|NP_114141.2| Length: 5635 Number of Matches: 4 PRLKRLNLQFNHIEHISDDAFADQRHLRSLNLGHNNLKVLSPKVFRNLISLEELYLNNNLLQILTNEHFSYLSSLKRLYLQWNSLQTLDHNTFLHSSSLELINLSHNKLEEINNHIFKNMIKLKSLILDNNAIRNIEPEAFQNLLELLEVTLENNLLTTLNVNHFITKKKLSKVSFFNNPFQCNCKIYWMYEAVNNGWSNIINLEKLTCNHSWENKTRNIIELKSEQFTCHGSWGAWENWSSCNKPCSNQMRYRTRLCYTNARSEYTGLCEGDATELERCSSSCTYGVLTNWEEWNECSTLSKNVYQIRKRFCFDPLTNFETTGCTEPLVEKRLCIKTLSFEETSWNNWSSWSTCDKECGLGIKTRERVCVRSVLKTKKRTCNENEIQIQENTCFNALCPTMTQWTEWYSISNCSATCGKGVLKKTRSCQNILNLTVNAQDFCLGENYKFVECYGNHELCTMKGSWSQWSLWSTCDTFSCKQYRSRKCYSHFVGNDVQNCSGVHEEEQTCASLFPCSAWNAWQQWSQCSHSCDLGYRKRKRLCINLNAINLKCIEEGVNLIEEKNEEIEECKLPKCFVAKWGTWGNWSECTSRGRELRTRQCLEENDFSQCEGPEKEKRPCKFEKVDSKQKEMVITKKTTICVPRYSIPNGKEIVKTIPNGIKAFYSCNKYYRLKGWEENDSPYCVPICGKPQHKSIRNSIKRARLLGGLPSVAHSWPWQVAIEVQTRKFGWKLYCGGSLLHDKWIVTAGHCLFDEDTRRRYKKTELQVFLGIHNISKRYEDPDLIFSVEYTAVHPKFNFDSLENDIGLIELKEKAKLSG

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Proteasome degradation: NEDD8-conjugating enzyme, p62/Sequestosomes (SQSTM), SUGT1>NEDD8_Hydvu ENA|HAAC01001015.1 TSA (PTHR24067:SF39, NEDD8-CONJUGATING ENZYME UBC12): Hydra vulgaris, contig asmbl_14013: 612, 333, 945 (+); identical to PREDICTED: NEDD8-conjugating enzyme Ubc12-like isoform 1 [Hydra vulgaris] Sequence ID: ref|XP_002156604.1| Length: 204; 43% identical, 60% similar to PREDICTED: probable NEDD8-conjugating enzyme Ubc12-like [Amphimedon queenslandica] Sequence ID: ref|XP_003385999.1| Length: 279 Number of Matches: 1; then closer to Saccoglossus, Neurospora crassa, …MAFIKHSRPLKTMHENFSGDLTKLNDYILNNIIGGKKVHSNISGQRVQQQHYLQLVKNISNISNNQAFILDSDVCNKFMLSISPNDGPYSGGCFLFFFNLPLNYPHAPPIVQCQGHIYHPNIDDDGEVCMSILDEWRNDSNDLLDCVQGLLNLFHHPNLEDPLSPYFSPNELNKTSFESNVKLSMSGGVIDGVAFDNVLLYNVF

>SQSTM1l1_Hydvu sequestosome-1 like 1 ENA|HAAC01018575.1 TSA (PTHR15090, SEQUESTOSOME 1-RELATED): Hydra vulgaris, contig isotig01531, 466 AAs, 94% identical / 96% similar to PREDICTED: uncharacterized protein LOC100211305 [Hydra vulgaris]; “The p62 protein, also called sequestosome 1 (SQSTM1), is a ubiquitin-binding scaffold protein that colocalizes with ubiquitinated protein aggregates in many neurodegenerative diseases and proteinopathies of the liver” (Bjorkoy et al. Methods Enzymol 2009).MSLFEKEVHMKVYYVENQHNNEIRKFSVENRMAANYKYILDKIRQVFTNLYEKDLDLFYKDKENDFISISSDIEFQQAFESINNGCLKLYVKKKLTKPAQSNKEHIGVSCDGCNSKIYGNRFKCTQCFDFDLCSLCYKKGEHPSDHEMLVIKEPRSSKHMCYSQLPFSHCWERYAHMNTNNSCSNKNASNNEENKPTASDQKFDSFQFEKMNNFKEIIKIFESMLGIKIDFYIESCQEKSDKVEKKEDFSEKLDSLIKVINERFGVPTEQMHTLVDDFIKQCDLKSNGTNSDKDINNSNNQVFRNNGDMNQANLSDKKDVSLENQLIEKDKEIVNPSDSLCHTNVESVPHLDPNNVSEVIKEQINPLDTLCPQTSDLQVDSSQEGLGNLIGHLYPQLETQQPSINPANDFIFVDKESIDHKESKLERSLRQMEAMGFDNEGGWLRQLLISKECSIDKVLDALTPAK

>SQSTM1l2_Hydvu sequestosome-1 like 2 ENA|HAAC01028739.1 TSA (PTHR15090, SEQUESTOSOME 1-RELATED): Hydra vulgaris, contig meta_rep_c19419, 456 AAs, 77% identical / 85% similar to PREDICTED: uncharacterized protein LOC100211305 [Hydra vulgaris]MSLFEKEVHMKVYYVENQHNNEIRKFSVENRMAANYKYILDKIRQVFTNLYEKDLDLFYKDKENDFISISSDIEFQQAFESINNGCLKLYVKKKLTKPAQSNKEHIGVSCDGCNSKIYGNRFKCTQCFDFDLCSLCYKKGEHPSDHEMLVIKEPRSFNHVYYSQFPFLHCWESFFSNKNASNNEKKNSTASDQKFDSSQFEKMDNNFKEIFKIFESMLGINVEFFMESSQVKSDETENVESFCKKLNSLIEVINERFGVDTELMHTFVDNFIKQYNLKCNERNSGKDINNSNNEVFRNNGGVNQTNMSNKNDVSIDKDKDLVKKNCLGSLCHTNVESVPHLDLNNASEVIKKQINPLGSLCPQTSKLQVDSSQEGLANFIGHLYRHLVTQQPPISIANDFELVDKESMDHKESKLERSLKQMEAMGFDNEGGWLRQLLISKDCNIDKVLDALSPAK

>SUGT1_Hydvu ENA|HAAC01025862.1 TSA: Hydra vulgaris, contig meta-ga_rep_c05922 (PTHR22904, TPR REPEAT CONTAINING PROTEIN); 100% identical to PREDICTED: suppressor of G2 allele of SKP1 homolog [Hydra vulgaris] Sequence ID: ref|XP_002156624.1| Length: 373 Number of Matches: 1; 41% identical, 60% similar to SGT1, suppressor of G2 allele of SKP1 [Xenopus (Silurana) tropicalis] Sequence ID: ref|NP_001016156.1| Length: 330 Number of Matches: 1; UNIPROT Q9CX34 (SUGT1_MOUSE): May play a role in ubiquitination and subsequent proteasomal degradation of target proteins. Probably associates with SCF (SKP1-CUL1-F-box protein) complex through interaction with SKP1. Interacts with S100A6. Interacts with HSP90. The CS domain mediates interaction with HSP90. Contains 1 CS domain, 1 SGS domain, 3 TPR repeatsMTGNLAADKFSAGNEAFADEDYDLAIQYYTEAINLDGENGAYYLKRCNARLKKEDFGGALDDANMSIKLNSGDGRAFQRKGSALFFLEDFDGALDAFKRSLEFDANNEQIKQSIRKCEAEINLKEVLKKNTEETQRNKTLIGLSNIHKANEKQDEVPPSITDDKTTVVPTSLKTKYDWYQTETHVIISILIKNIKEKDVSCHFGDKTLSVTIKLSQENDYSLELDLSQNIVPHQSLFQVFSTKLEIKMKKESGIRWDTLEEDHTKITVIKSPSKSDTVNPHKYPSSSHFVKNWDLLAKQVEEEEKNENKEGDGALNALFQQIYADGSDEVKRAMNKSFQESGGTVLSTNWNEISKEKVEIKPPDCMEYKKYEY*

RECEPTORS: G-Protein Coupled Receptors (GPCR)>D(1C)Rl_Hydvu ENA|HAAC01024313.1 TSA (PTHR24249, HISTAMINE RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR): Hydra vulgaris, contig meta-ga_c01528; no Hydra hit, 56% similar to PREDICTED: D(1C) dopamine receptor-like [Danio rerio] Sequence ID: ref|XP_005158584.1| Length: 447 Number of Matches: 1MNGTLCNNTSCKDNVMLTLPSDVKFILGVDVFIIFIALVLNIIGISLLFTRKLKNLSPQNIFIMHMSFVSIINVFNNAVAVHWKYQSSRFTKTFVAVYYFAHMAYIINLCLLSLDRFMFVAFPFKYRTKMTNFIVFCSLVLLWLFSIIFGLLIRYGGIANDWFFSNAAYLYNGFVIALAFCIYAYIVIKIHFSSLKNDNQLVNKKAKKLFIMPFLIISSFFMFVFLPHLIAENVKIKSKNTKKLLLLALIGINLLNNVSDPIIYIYLQPDAWKKLVLLTRKFKGLFTFQSFNFLNHKKRAASLTKYQSFEINIETIEP

>BRS3l_Hydvu ENA|HAAC01014232.1 TSA (PTHR24242, G-PROTEIN COUPLED RECEPTOR): Hydra vulgaris, contig CUFF.3493.1: 999, 112, 1111 (+); identical to >gi|449687220|ref|XP_004211395.1| PREDICTED: bombesin receptor subtype-3-like, partial [Hydra vulgaris]; Uniprot P32247

(BRS3_HUMAN) Role in sperm cell division, maturation, or function. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.MDGNTTNRYPFPIRSWEIFWYGSIAVLGTVGNGVVMMVMILNKNIKMTSFNFTIFSLAFTDFLASFIGLPNYILSTSIFNHPDGLKGDWLCKLFTGYFWPFFFLDVSVFILVYIAIERRKAILDPIGCQQNRINNYSFFIILLIVIFASILGIPTVYGMVYNIEKNIVGNCCTYKYSYLQSICIYFAVFILDTIIPAVAMIVCYRQISSSLGKSNVLLKASIHLNNQRKNLNKTTLVFGSKFKTVQTMKIVILAFFACIVPNHLLYLLSLISVRGLEWNSVVSQIGVLIRFSNTCVNPFIYSIKSKQFKKNFWFVYDTRIKGRSNYKILNRTL

>NPYR4_Hydvu ENA|HAAC01002535.1 TSA (PTHR24242:SF99, BRAIN PROLACTIN-RELEASING PEPTIDE RECEPTOR-LIKE PROTEIN 1): Hydra vulgaris, contig asmbl_20471_ext: 1194, 3, 1197 (+); 100% identical to PREDICTED: neuropeptide Y receptor type 4-like isoform 1 [Hydra vulgaris] Sequence ID: ref|XP_004208934.1| Length: 398; ANMTITTTVLNSTVATSSTPIWFPVRDITLSEWCIVVSFALILSTGVLGNAFVIYVFGYKRKSNRRSTTELLIFYLGIIDFLSSLLNPPLYIYWILTNYRRWDFGYLGCQIIPSLGPIMTSASCGVLLIIAVDRYIAIVAPFSGELTPKTVTIVFFFDIVVSICFYLHYILALRIHPKYKYCFVPDVADYKYGIPNCVFVVLRLCLFATVFSFTNVKIFETLRQCNGNSTSKEIRVQRLKQSKRIMGLLVTMGLVFTFLVFPRELFYLVYNLSWMVSKNGVKFNSTLYQINSWLKVAHTANSCANVFIYSHMQIMYRKQIMRVFAYFGCCKKTFSHQSFSITFTSFMRDKSRASLRKTKKEFKKILLIDNEDSISSGDAVFFQRAQQWKKRQRYDSMF

>CSL3lb_Hydvu ENA|HAAC01018525.1 TSA (PTHR12011, G-PROTEIN COUPLED RECEPTOR ??): Hydra vulgaris, contig isotig00832 5’3’ frame 3; best hit on NCBI: 95% identical to L-rhamnose-binding lectin CSL3-like isoform 2 [Hydra vulgaris] Sequence ID: ref|XP_004209686.1| Length: 207

Number of Matches: 1; besthit on EBI: 42% identical 59% similar to L-rhamnose-binding lectin CSL3-like [Strongylocentrotus purpuratus] Sequence ID: ref|XP_788214.1| Length: 309 Number of Matches: 3; Drosophila latrophilin related: Forms a heterodimer, consisting of a large extracellular region non-covalently linked to a seven-transmembrane moiety; MRRNLQISRSSILLQTFFKVVRSCEGNDLKIDCNDGGTIEVVYANYGRTSSGICPGSMDSNTKCDNHKKSLQVVRNSCSSRTSCVIKAVNAVFGDPCVGTYKYLEVQYYCKPQLHVVQACEGTDLKIDCKGNGKIEVVYANYGRTSSGICPGSNDSNIKCNNQINTLQIVRNSCSAKFSCVISAANSVFGDPCVGTYKYLEVKFYCKL

15



>CSL3la_Hydvu ENA|HAAC01018525.1 TSA (PTHR12011, G-PROTEIN COUPLED RECEPTOR ??): Hydra vulgaris, contig isotig00832 5’3’ frame1: besthit: 98% identical from 1 to 123 to L-rhamnose-binding lectin CSL3-like isoform 1 [Hydra vulgaris] Sequence ID: ref|XP_002157223.2| Length: 215 Number of Matches: 2; MMKKISIILLLSFVFIDIELTTGIPLIAQTCEGNDLKIDCKGKGTIEVIYANYGRTSSGICPGSMDSNTKCDNHQNSLQVVRNICSSKSYCVIKAANAVFGDPCVGTYKYLEVQYYKWSDHVKEMILKLIVMMEEQLKWFTQTTAEHRLVFVLAPWIQIQNVITIKNLYKLFVTAVHQEPLVLSKLLMQCLVIHALEPTNISKSNIIANHNYMLYKLVKGQILK

>CSL3l1_Hydvu ENA|HAAC01018525.1 TSA (PTHR12011, G-PROTEIN COUPLED RECEPTOR ??): Artificial reconstruction between the two frames from blastp!MMKKISIILLLSFVFIDIELTTGIPLIAQTCEGNDLKIDCKGKGTIEVIYANYGRTSSGICPGSMDSNTKCDNHQNSLQVVRNICSSKSYCVIKAANAVFGDPCVGTYKYLEVQYYKVVRSCEGNDLKIDCNDGGTIEVVYANYGRTSSGICPGSMDSNTKCDNHKKSLQVVRNSCSSRTSCVIKAVNAVFGDPCVGTYKYLEVQYYCKPQLHVVQACEGTDLKIDCKGNGKIEVVYANYGRTSSGICPGSNDSNIKCNNQINTLQIVRNSCSAKFSCVISAANSVFGDPCVGTYKYLEVKFYCKL

RECEPTORS: Tumor Necrosis Factor Receptor (TNFR)>TNFR16_Hydvu ENA|HAAC01036244.1 TSA (PTHR23097:SF107, SUBFAMILY NOT NAMED): Hydra vulgaris, contig miradenovo_c30779: 969, 3, 972 (+); also named low affinity p75NGF receptor; 97% identical, 98% similar to > p75-like protein [Hydra vulgaris] Sequence ID: gb|ACY71872.1| Length: 309 Number of Matches: 1; 97% identical to PREDICTED: tumor necrosis factor receptor superfamily member 16-like [Hydra vulgaris] Sequence ID: ref|XP_004209206.1| Length: 309 Number of Matches: 1>tr|D1M870|D1M870_HYDVU p75-like protein OS=Hydra vulgaris PE=2 SV=1; TNF Receptor family; 93% identical, 94% similar to >tr|T2MHT0|T2MHT0_HYDVU Tumor necrosis factor receptor superfamily member 16 OS=Hydra vulgaris GN=NGFR PE=2 SV=1. TNFR16_Human: P08138. Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake By similarity. Low affinity receptor, which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells. Homodimer; disulfide-linked. Interacts with p75NTR-associated cell death executor. Interacts with TRAF2, TRAF4, TRAF6, PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1, which bridges NGFR to NTRK1. Interacts with BEX1 and NGFRAP1/BEX3. Interacts with KIDINS220 and NTRK1. Can form a ternary complex with NTRK1 and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1. Interacts with NTRK2; may regulate the ligand specificity of the NTRK2 receptor. Interacts (via death domain) with RAB31. Single-pass type I membrane protein. Death domain is responsible for interaction with RANBP9. The extracellular domain is responsible for interaction with NTRK1MAKCLLFFTACFISTVVNIPLNTNCAPGEESFLMGCKSCEVGYYSRDGLVCKKCSTCLDIQTLLRECISTEDTFCLCPEGTYLQNNTICSRCQKCEKGTFQVVDCSHNFDRVCQKCPRGQTTNGTNSKTCFVKPNPPDLVETKKETVIKWPYVVGGAALVSVLCVVFLIYYLLVKRFKTRKRFIDCRGKNVSLLNENVLSDCATEFNIASSSECANQTWQKQLKDVPADVLFELGKKLNPAFANNWKVLAGQLGYTYEDIAHFDLSPKTATVDLLHDWSTGENATLNILYNKLILINGGRSRIVRPYL

RECEPTORS: Toll-Receptor Related (TRR)>TRR1a_Hydvu ENA|HAAC01012396.3 TSA (PTHR24365, TOLL-LIKE RECEPTOR): (HyTRR-1) 493 AAs; similar to uncharacterized protein LOC100209303 [Hydra vulgaris] Sequence ID: ref|XP_002169105.1|Length: 387 Number of Matches: 1, 100% identical; TRR1 related; 37% identical 56% similar to toll-like receptor 4 [Homo sapiens] Sequence ID: gb|AAY82270.1| Length: 839 Number of Matches: 1 (C-terminus)IIAFQLFGKGHCTLDECVTYLNRENLTQPDVVRRNAEACCPYLRVGFPPLNLTSLGSKYKILTKKTIDQLYTSTLTPQILHANENVITDDFDFRTLFCHSMANVSDMKFTTQEELSFRNFHQKWKNVHSYQLSCGILVVFSPVKLCQHGFFFKCFVKYDKTYLYVKTATIIYANRPYLSISSSNDDGKTLKVTCKYANLINPLFLNITFSHNDQLINGNKDFLINPTEFFENISARRFDLKRTLSILNPQFFNDNFSCVLSDDKCGIVASQSLSLFQDKKAGSTPTFLSDGLWVVLIGFLLLLFFFLKIKSKWCKSLKKSGKIQEDLTVVVNDHRNENELHFMSSITNVEQSMTCFKQNITNPDQRTNDVFISYSSQNREWVNNTLLFELEKRNISVCIDYRDFVLGEYISKNILDGMHNSRKTIVVISSDYLKSNYCKEELQTASQGHSVIFIMIEKCKLPRYLKQQLSKNQVFEWEDNERFWKNLVLAIHX

>TRR1b_Hydvu ENA|HAAC01029717.1 TSA (no PTHR, see TRR1a): Hydra vulgaris, contig meta_rep_c24724; isoform of TRR1a (HAAC01034436) and TRR1b (HAAC01006727); highly similar to >gi|526117447|ref|NP_001267771.1| Toll-receptor-related 1 [Hydra vulgaris]; 37% identical 56% similar to toll-like receptor 4 [Homo sapiens] Sequence ID: gb|AAY82270.1| Length: 839 Number of Matches: 1 (C-terminus)KKLTSLGSKYKILTKKTIDQLYTSTLTPQILHANENVITDDFDFRTLFCHSMANVSDMKFTTQEELSFRNFHQKWKNVHSYQLSCXILVVFSPVKLCQHHSFFKCSVKYNETYLHVKTAAIKYAMEPFNLSISRSNDDGKTINVTCAYANFRKPIFLNITFSHNDYRLINDSRTFLINPIIPLYNSGRDRFSLQRTLSILNPQIFNDTLSCILSDDKCGIVSRQNFSYLQVKTKKAGSTPSFLSDGLWVVLIAFLLLLLLFLKIKSKWYDGMCKGSLKKVQGKIPENSIAIVNDKNYEKEMYLQKKCISSITNVEQNMTCFEQNITNPEQKNNDVFISYSSQNREWVKNTLLFELEKRNISVCIDFRDFVVGEYISKNILDGMYNSRKTIVVISSDYLKSNYCKEELQAASQGHSVIFIMIEKCKLPRYLKQQLSKNQVFEWEDNERFWKNLILAIRS

>TRR1c_Hydvu ENA|HAAC01006727.1 TSA (no PTHR, see TRR1a): Hydra vulgaris, contig asmbl_37895; 98% identical to >gi|526117447|ref|NP_001267771.1| Toll-receptor-related 1 [Hydra vulgaris]; shorter isoform of TRR1a (HAAC01034436) and TRR1b (HAAC01029717); 35% identical 56% similar to toll-like receptor 4 [Homo sapiens] Sequence ID: gb|AAY82270.1|Length: 839Number of Matches: 1 (C-terminus)IHHYPPTNKINRIVKYLYFLSVNLSISRSNDDGKTINVTCAYANFRKPIFLNITFSHNDYRLINDSRTFLINPIIPLYNSGRDRFSLQRTLSILNPQIFNDTLSCILSDDKCGIVSRQNFSYLQVKTKKAGSTPSFLSDGLWVVLIAFLLLLLLFLKIKSKWYDGMCKGSLKKVQGKIPENSIAIVNDKNYEKEMYLQKKCISSITNVEQNMTCFEQNITNPEQKNNDVFISYSSQNREWVKNTLLFELEKRNISVCIDFRDFVVGEYISKNILDGMYNSRKTIVVISSDYLKSNYCKEELQAASQGHSVIFIMIEKCKLPRYFKQQLSKNQVFEWEDNERFWKNLILAIRS

>TRR1d_Hydvu ENA|HAAC01034436.2 TSA (PTHR24365, TOLL-LIKE RECEPTOR): (HyTRR-1), Toll-receptor-related 1 [Hydra vulgaris] Sequence ID: ref|NP_001267771.1| Length: 397, Number of Matches: 1: 113/1 -> 513/397, NEW N-term DOMAIN from 1-113? Highly similar to ENA|HAAC01029717, to ENA|HAAC01006727_3; NCBI: toll-like receptor 4, partial [Mus musculus domesticus] Sequence ID: gb|AGY29686.1| Length: 748 Number of Matches: 1MLVQVIIVVFQLFEIGDCTLDECVTYLKRENLTQPDIVKRNAEACCPYLRGGFSLLNLTSLGSEYRRFDKKSIDQLYTSTLIPKILHTNSCVILREIEFRTFFCHSTANVSDMDFTTQEGLSFRDFHKNWKNVHSYQLSCGILVVFSPVKLCQHHSFFKCSVKYNETYLHVKTAAIKYAMEPFNLSISRSNDDGKTINVTCAYANFRKPIFLNITFSHNDYRLINDSRTFLINPIIPLYNSGRDRFSLQRTLSILNPQIFNDTLSCILSDDKCGIVSRQNFSYLQVKTKKAGSTPSFLSDGLWVVLIAFLLLLLLFLKIKSKWYDGMCKGSLKKVQGKIPENSIAIVNDKNYEKEMYLQKKCISSITNVEQNMTCFEQNITNPEQKNNDVFISYSSQNRE

16


http://www.ncbi.nlm.nih.gov/protein/221102403?report=genbank&log$=protalign&blast_rank=1&RID=C429WCEE014


WVKNTLLFELEKRNISVCIDFRDFVVGEYISKNILDGMYNSRKTIVVISSDYLKSNYCKEELQAASQGHSVIFIMIEKCKLPRYLKQQLSKNQVFEWEDNERFWKNLILAIRS

>TRR2l_Hydvu ENA|HAAC01035183.1 TSA (PTHR24365, TOLL-LIKE RECEPTOR): (HyTRR-2); NEW HYDRA TLR?, deltablast best hist: toll-like receptor 3 [Paralichthys olivaceus] Sequence ID: dbj|BAD01045.1|Length: 961 Number of Matches: 1: 7/780 -> 97/873 52% similar, 3e-22, hits TLR22 from numerous species: Toll-like receptor 22 precursor [Takifugu rubripes] Sequence ID: ref|NP_001106664.1|Length: 935 Number of Matches: 1: 52% similar, 5e-22 HVDIIDSYYFAFKENGKRKFRKKEKTYDVNICYAPEDREWVINTLVFKLERAGIKTFVNIRDDTPGNFFAENIMDAIENSNRTIVVMSPDFFKNIYAIKLCKLDCRIK*

>TRR6l_Hydvu ENA|HAAC01020205.3 TSA (no PTHR): deltablast: no HIT on cnidarians @ NCBI, 1st hit: Toll-like receptor 6 [Tupaia chinensis] Sequence ID: gb|ELV10441.1|Length: 327 Number of Matches: 1, 48% similar, 1e-19 MLILLIAIILLLKKIEKKKFRKKEKTYDVNICYAPEDREWVINTLVFKLERAGIKTFVNIRDDTPGNFFAENIMDAIENSNRTIVVMSPDFFKKYMR*

RECEPTORS: Nod-like Receptors (NLR)>NLR1N_Hydvu ENA|HAAC01015533|HAAC01015533.1 TSA: Hydra vulgaris, contig CUFF.6382.1 (no PTHR): Location:1..341 length 103; 100% identical to NLR type 1 [Hydra vulgaris] Sequence ID: ref|NP_001267803.1| Length: 688 from 1/1 -> 103/103 Death Domain MDENILQNQQNRYLFSRSVGIDWKDLGRCLQILDSYLDVIDIESKNCCDKAYQMLTKWTEKENPSLNELKNALQTMEKNDLMKTLEDLQIRSSKEIEKSNLVK

>NLR1C_Hydvu ENA|HAAC01026882.1 TSA: Hydra vulgaris, contig meta-ga_rep_c09049 length 423 (no PTHR); 99% identical to NLR type 1 [Hydra vulgaris]; Sequence ID: ref|NP_001267803.1| Length: 688 1/266 -> 423/688; 23% identical, 46% similar (score 41.6!) to PREDICTED: NACHT, LRR and PYD domains-containing protein 12-like [Danio rerio] Sequence ID: ref|XP_695160.6| Length: 936 Number of Matches: 1MFIIDGLNEFKYFDQLISNTHCSSQEIPILNVFTEIYKYKAVISGRVNTISQYENVVTRYKDKLTIRVMGYNENGIKYYLRNNLIKKTKCRVKTMLKESSIAKTMAKVPFFLSCMCTIVADLKVKYNFINLTMTDLYAYNFLYFFQRHIFNENHEPIFKIMENNLNKQCILNICKIAYIFFIENKTTFSDIEIQTFISGFDQMESGLLEKVFLMKSGFIEKIETNFGYHYRFCQTAMIELCVSVHAYYSYSGKKIMENQKLKDCFSIIYGLLNTNENSFIKYLANLTNSNTEKISLNHVIDVIPKEINCDREYQDKQKLFMQCFFESQATITDDIKASIDERKWKILINGTKTSYEVLCEKYFVNHLVNSGGKLTSLEIDKNLLTDKEKDLIKQCSRNVKDIRIKRSYRFFIDQFTKRWIRSE

TNF Receptor Associated Factors (TRAFs): TRF-1, TRF-3, TRF-6 related>TRAF2l1_Hydvu ENA|HAAC01008896.1 TSA (PTHR10131:SF74, PROTEIN TRF-1-RELATED): Hydra vulgaris, contig asmbl_7622 (Panther) Full-length; identical to gi|449687576|ref|XP_002153777.2| PREDICTED: TNF receptor-associated factor 2-like [Hydra vulgaris]MFLLLKKFLFLVFLVFIGNMIASIVIVRQKATDYLINHLRLVKFVEKTPLSLCCHVCKKILIRPVQWDCGHRSCESCFRSGIYCKEDDETVLSCFPDNQALKEILNLSCYCLYKNDGCYWNGFCHELEEHLKICSFIETLECPYKVISCKVIGSKKTVLNHQVQELVYHSALLSVFFKSECESFILLKSKISDLKEYEYLHSYKYDDDYNVDKLSSEINALSKKRNSLKKFQSFVGDIDRIEQQIKYLLSFFNKKSFTENLHDAENRVARAEKENELIKTRLNDIRYKILLINSVTNDGSYLWKIDNFSKKLEDALAGRTIELFSPPLMTDPSGYRFCAIVMLAGDLKFNKYSQNFISVYISILPSPFDEVLKFPFPYDIDISLVSVIKGNQNHSKKLKPSGHISFQKPYLPMNQPVGFSMFCSHDNLYSGGYIKDDAIFIKFNVLK

>TRAF2l2_Hydvu ENA|HAAC01026938.1 TSA (PTHR10131:SF61, TNF RECEPTOR-ASSOCIATED FACTOR 3): Hydra vulgaris, contig meta-ga_rep_c09209 (Panther) Full-length; 99% identical to >gi|449681025|ref|XP_002169387.2| PREDICTED: TNF receptor-associated factor 2-like, partial [Hydra vulgaris]; 45% identical, 65% similar to Human Chain A, Structure of TNF Receptor Associated Factor 2 In Complex with a Peptide

From TNF-R2 Sequence ID: pdb|1CA9|A Length: 192 Number of Matches: 1 (83/8 -> 261/188); 56% similar to TRAF2 Mouse P39429 (TRAF2_MOUSE) 103/283(36%) -> 161/283(56%) Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Isoform 2 does not seem to mediate activation of NF-kappa-B but inhibits isoform 1 activity. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE. Has very low E3 ubiquitin ligase activity in the absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is strongly activated by cytoplasmic sphingosine-1-phosphate. Homotrimer, and heterotrimer with TRAF1 and TRAF3 (via TRAF domain). The domain containing the RING-type and the first TRAF-type zinc finger can also form homodimers (in vitro). Interacts with TNFRSF1B/TNFR2, TNFRSF4, TNFRSF5/CD40, CD27/TNFRSF7, TNFRSF8/CD30, TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF16/NGFR, TNFRSF17/BCMA, TNFRSF18/AITR, TNFRSF19/TROY, TNFRSF19L/RELT, XEDAR, EDAR, Epstein-Barr virus BNFL1/LMP-1 and IL15RA. Interacts with CDK9, CSK, MAP3K1, MAP3K5, MAP3K11, MAP4K2, RIPK2, TNIK, TBK1, SPHK1, TRAIP, TANK/ITRAF, TDP2, MAVS/IPS1, TICAM1 and TRPC4AP. Interacts with CASP8AP2, NFATC2IP, PEG3 and HIVEP3. Interacts with CYLD, USP48, IKKA and IKKB. Interacts (via 'Lys-63'-linked polyubiquitin chains) with TAB2 and TAB3. Interaction with TA3 is facilitated under ER stress conditions, such as treatment with tunicamycin, and may promote TRAF2 phosphorylation. Interacts with CASP12 under resting conditions; this interaction is reduced in ER stress conditions. Interacts (via zinc fingers) with DAB2IP (via C-terminus PER domain); the interaction occurs in a TNF-alpha-dependent manner. Interacts with ERN1; the interaction requires DAB2IP. Interacts with DAB2IP. Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain). Interacts with CARD14 By similarity. Interacts with TRAFD1, TRADD and TNFAIP3. Interacts with BIRC2 and BIRC3 N-terminus; a single BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 and TRAF2, or a TRAF2 homotrimer. Identified in a complex composed of TRAF2, TRAF3, BIRC2 and/or BIRC3. Interaction with BIRC2 and/or BIRC3 is essential for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with MAP3K14 and RIPK1. Interacts with PTPN2; probably involved in tumor necrosis factor-mediated signaling.MVFVQEMFVKQMTLKNEVNKLIKENLELRQQLELVKKCYQEINDLKKTVQIQVDEIASIFQALNLQVNDLKEINFKSTPVVDFSKKLSVVERSQEKLNETYSDLQLSQQILENTSYDGHLLWKISSYKQRSMAAMSGTIPALHSAPCYTSRFGYKYCLRLYLNGDGAGKGSYISLFFVLMKSDYDSLHKWPFQNKVTFRLRAKNPEYDIVESFTPDKNSSSFIKPVREMNIAAGVPLFAKKSDINENFILDDAIFIESKVHL

17


http://www.uniprot.org/uniprot/P39429#P39429

http://www.uniprot.org/uniprot/P39429#P39429-2


>TRAF3a_Hydvu ENA|HAAC01024082.2 TSA (PTHR10131:SF61, TNF RECEPTOR-ASSOCIATED FACTOR 3): Hydra 336 AAs, TNF receptor-associated factor 3-like [Hydra vulgaris] identical to gi|449671572| ref|XP_002161248.2| PREDICTED: TNF receptor-associated factor 3-like [Hydra vulgaris Length: 336 Number of Matches: 1, 100% 1/1 -> 336/336; hypothetical protein BRAFLDRAFT_85024 [Branchiostoma floridae] Sequence ID: ref|XP_002592152.1| Length: 473 Number of Matches: 1, 55% similar, 1e-48, 53/195 -> 330/473; TNF receptor-associated factor 3 [Crassostrea gigas] Sequence ID: gb|EKC37852.1| Length: 581 Number of Matches: 1, 48% similar, 1e-34, 53/234 -> 328/573; MQEDEENTHNIEMPLESRTGPEGQSSRKILSSNEEASKIVEKSEDMMETLKYCKFSKIGCKFTGNRFEVDLHMDIASEKHLDYVLKSIQEIKSEYIKKENKVIAKHDSKLKVLQEYICKQNNAIKDLHETNRQLETSARDFEVQLTSISASNSKLIDEMNRLKIQLITLQEELLEHKDINFTGCLMWKITEVSVHITNAVKKQNLSIYSKPFYTSRYGYKIRAQLFLNGLGCNTGQYASIYFHLLPTDHDNILSWPFRHKISFSLLDQSGDKTKNISYALCPSVDDKQFKQPSVNMSEGKGFNKFFSIEELKRDNYVKQDCAYIKIRIHCKTSSSN

>TRAF3b_Hydvu ENA|HAAC01023179.2 TSA (TRAF 3a isoform), short isoform of 24082, identical to 04672 in C moiety; Blastp: identical to gi|449671572|ref|XP_002161248.2| PREDICTED: TNF receptor-associated factor 3-like [Hydra vulgaris]KNILLMQEDEENTHNIEMPLESRTGPEGQSSRKILSSNEEASKIVEKSEDMMETLKYCKFSKIGCKFTGNRFEVDLHMDIASEKHLDYVLKSIQEIKS

>TRAF3c_Hydvu ENA|HAAC01004672.2 TSA (TRAF 3a isoform), very short isoform of 24082, identical to 23179 in C moietyMRLLQIFSVFVNFSKIKVATTAEAKATTAIEASKIVEKSEDMMETLKYCKFSKIGCKFTGNRFEVDLHMDIASEKHLDYVLKSIQEIKSEYI

>TRAF4a_Hydvu ENA|HAAC01033214.3 TSA (PTHR10131:SF74, PROTEIN TRF-1-RELATED): TRAF 4, 531 AAs, 3 domains: RING (N-term), zf-Traf (2x central), MATH superfamily (MATH-TRAF-C last third) contains TNFR binding site; TNF receptor-associated factor 4-like [Hydra vulgaris] ref|XP_004207529.1|Length: 531 Number of Matches: 1: 100% identical; MTANNVEEQHQENDYIFSQADQLIKENKVEEQPTFLNEPNEIESETTVNQESEPPTEKDEAIKVTKEYEDKEYFEKPKYIGEDEKTSVNSLSISQLRDSPTTLPEERLKFTLKHPLKSDHTCPQCNEAMRYPVQFSECKHRVCSACFHEFFRTEPRCPVDQGKINREKAFLDKTLTETIMKLEILCNFEEWGCKWEGTFGEGQSHFEKCDYTNILCNHDCGAKFQRRFLQRHLDKDCPKKIISCAFCEERCLREEKKAHLEDCQKVPLPCPNKCDKKLTIPRDELDNHIEVDCPRTKVLCQFEEIGCPHRCSRERLQKHNKTGIIAHVRLLYDVVMKQSQRLDQHHELLHDHGALLEAHQALIDEIQQSAKTQLVWRIEEFSRKMKEAKSGNVTTLFSPPFHTSKHGYRMCASLCLNGDGKGKGTHISVFVSILKGAFDSLLKWPFDYRIKFYLLDQNPVIEKRSHKKFNIKPNPCQENLPFLGCPKMEKNASFGAAKFCKQSDLEDQPTLVKDDVIYLKISCDCGAGAEF

>TRAF5l1_Hydvu ENA|HAAC01015844.1 TSA (PTHR10131:SF74, PROTEIN TRF-1-RELATED): Hydra vulgaris, contig CUFF.7061.1 : Location:1..408 (Panther) PARTIAL; similar but NOT IDENTICAL to >gi|449667148|ref|XP_004206497.1| PREDICTED: TNF receptor-associated factor 5-like [Hydra vulgaris]EEVECTYFYDKFANKEIQALEFYCPFNENCKWSGQLIKLKEEHLNSCDYKISICDKCGEEVIQKSLNEHCLNYCSHSFFTCQYCDEKISVKDKKAHLCLKLSVTCFLDCGTTFLYEDIITHLNQCNNLQNVCIYR

>TRAF5l2_Hydvu ENA|HAAC01026575.1 TSA (PTHR10131:SF70, SUBFAMILY NOT NAMED): Hydra vulgaris, contig meta-ga_rep_c08032 : Location:1..702 (Panther) might be partial; similar but NOT IDENTICAL to >gi|449667148|ref|XP_004206497.1| PREDICTED: TNF receptor-associated factor 5-like [Hydra vulgaris] (low score -53, high e-value 3e-06); 24% identical 47% similar (1/110 -> 113/226 to PREDICTED: TNF receptor-associated factor 2 isoform X5 [Gallus gallus] ref|XP_004945780.1| Length: 498MKEIQALEFYCLNFDICLWKGPLNEFNVHLQKCEKYKNEIIRKSLDEKGFKNCSHSFIICESCNEKILVKDKQLTSSYEYHHASHLSSHNHLFMVLIQQIVTEQTQLKNEVRDLQRQNFDLHCQNHNLLQLFSQNHDFSCLNQ

>TRAF6l_Hydvu ENA|HAAC01019586_1 (PTHR10131:SF52, TNF RECEPTOR-ASSOCIATED FACTOR 6): previously named TRAF-4, 435 AAs TNF receptor-associated factor 4-like [Hydra vulgaris] ref|XP_002168453.2|Length: 114 Number of Matches: 1: 2/1 -> 110/109, 54% similar 2e-50; BEST non-cnidarian HIT: TNF receptor-associated factor 4-like [Aplysia californica] Sequence ID: ref|XP_005107744.1| Length: 358 Number of Matches: 1 43% similar, 6e-20, 1/1 -> 290/287; then TRAF4 Xenopus, TRAF4 Human …; DELTABLAST TNF receptor-associated factor 6 [Gorilla gorilla gorilla] ref|XP_004051013.1|Length: 471 Number of Matches: 1: 36% similar, 1e-43; 2 domains: RING (N-term), MATH superfamily (MATH-TRAF-C last third) contains TNFR binding siteMDGYDADFVNEVPSDLECGICLFVVREPVQILACGHRFCSHCFENLKKLPADRLRCPKDNGSIDTKMVFPDTAALRTVSNLTVKCSKTGEGCLWQGALRELENHLKDCSLNNPKNLIQEHMLNQISVLEEAFKKKDQEYLHLKNENFRLEQEFVKFKKEMESFTTSTSIRLDELLVSYNDLSSRLQQIEKLKKEDSMTYNLPSQNVPPRIVPPKVINLVQKPVPCYVWKMNRNSGSRQTSPKFYSSDKGYLCQLKARKSIHLCLDILKGDFDRQLAWPFNMKVEFVCFNKFLSERHSLVYPLKKKDGTLSAQAHASYEYAVFLTPAVMNSCIVDDVISVEVYIS

>TRAF6_Hydvu ENA|HAAC01027712_2 (PTHR10131:SF52, TNF RECEPTOR-ASSOCIATED FACTOR 6): TRAF6, was PARTIAL so far in Hydra, 515 AAs 3 domains: RING (N-term), zf-Traf (2x central), MATH superfamily (MATH-TRAF-C last third) contains TNFR binding site; deltablast on cnidarians: 1) predicted protein [Nematostella vectensis] ref|XP_001640836.1|Length: 482 Number of Matches: 1: 54% similar, 4e-110; 2) partially identical to TNF receptor-associated factor 6-like [Hydra vulgaris] ref|XP_004206538.1|Length: 232 Number of Matches: 1: 100%, 301/18 -> 515/232; Deltablast: TNF receptor-associated factor 6 [Mus musculus] ref|NP_033450.2|Length: 530 Number of Matches: 1: 51% similar, 4e-112MLSKDNSATEEXFQQGYDEHFDPPAPDVYECPICLLVLNAPVQTECGHRFCRGCILKVLREGRPNCPIDNYSINEEQIYPDNFALREILELKVRCQNSKTHNCKWLGSLKSLKEHMMSCEYNLFPCSNNCGEKMTRNALDKHILNDCPKRVISCEYCKLKIVFKKLQDHYERCEGFPVNCPNVCEVVVIPRGKLKIHMEVECSRAILKCSYKDTGCEFQGTRDEVANHLKTENHQTMLLQMLCDLKLKVANQEKVIESFKEKEITFNKEFQSSNGAGYPFSLKPEASIVGRFDELEKKINQVKATSEVCRSELKHTRSELESRIESISIEVKAQNEVINEVSARTWKGNFIWRISNFDQLFRQALSGEVPAIHSLPFYTGVPGYKMCLRINLNGIDSGAGTHVSMFVHMMQGEFDSLIEWPFPGNVIFTILDQDTRDPQHVCETLTARPTLQAFLRPKINRNHKGYGYIELIRHTTLRTRGYISNDTLLVRVDIKMPPTR

TRAFFICKING: ExoC>EXOC7l_Hydvu ENA|HAAC01013028_6 102 AAs, exocyst complex component 7-like [Hydra vulgaris] Sequence ID: ref|XP_004208445.1|Length: 787. Wiki/Uniprot: The exocyst is an octameric protein complex involved in vesicle trafficking, specifically the tethering and spatial targeting of post-Golgi vesicles to the plasma membrane prior to vesicle fusion. It is implicated in a number of cell processes, including exocytosis and also cell migration and growth. The exocyst is composed of eight subunits that aggregate in a polar fashion. In mammalian cells and in Saccharomyces cerevisiae, there are eight subunits: EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7, and EXOC8 (formerly known as Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84). 2 papers on “exocyst complex component & immune”: Chien et al. Cell 2006: These observations define the mechanistic contribution of RalGTPases to cancer cell survival and reveal the RalB/Sec5 effector complex as a component of TBK1-dependent innate immune signaling. J Immunol 2011: Ral GTPases regulate cell-mediated cytotoxicity in NK cells. MIVPSPNLPPGTTLPQPLPTESTPTISSISICHIASAPKSSQKSPCLQTTFNIVVTPATQKEIQKEVAKQLQSAQSFGSTLQQMFRIQHVDTKKRKNVDVPX

18



TRANSCRIPTION FACTORS (bZIP, AP1): AP1, Jun, ATFs, CREB, CREB like, Fos-related >AP1_Hydvu 1027715 ENA|HAAC01027715.1 TSA (PTHR11462, JUN TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, contig meta_rep_c14288: 1311, 96, 1407 (+) MLSGTLPLNEKFLSMEXVLDTTFYSDDFLTRTLTTSVLYDKSQLDLTFVENNNCLPSKRPQYESTVESPNLDFLKLGSPDLEQMFMNINENDSNFSSEDKSDSSAFSLDDDFVSTENCFTDALQQLHDKQEILPTDFSGTNCNNRVGKENLHSKILQGKRKPISSPMNIQKLRTQNPMKQLYNPNQQRRNNFQHPCSHPPNKNQHRLNNLAVHHQNNISHLSISEQMALNNQLTMMNNMNQSINAHHMQQQHEIAFLTQAMGFQSDREPSLNYQNDRTMINSNGFQSQHNVPSQVPSQLQQKLLEHQLMQQQIGASYQNNNNNTTHHVPQIDSINGLGIDEGTLKMLMENPHMVPVNLELQELIKRERKKLRNRVASSKCRKRKLEREGRLEDKVKDLKEKNIELNAVANALKQQICDLKQRVMDHVGDGCQIVLPP

>Jun_Hydvu ENA|HAAC01033412.1 TSA (PTHR11462, JUN TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, contig miradenovo_c11933: 1065, 152, 1217 (+) MSQVAFYDRLVMSQQNYDKSALSLNLNGGRSAVSSRKRKFLQPSAALLQSPDLKLLKLGSPELEKLIIQNNGFIPTPTIGNTSFTQVGDHVEDQESFARGFIEALQKLQQENDVKDSPLTKAWNFSRISNLNQTAISSSLPTYQQITASNSLPNVSKWGQVDHNLNTVPVITANGNHYDNQSQLNSIKYSTATSVDVASTIGLDSLPKSNYYISKSQQCNIERTSHSKINSDLYPPSNNSLVSEIKTEDDMPPSVGSSTSSVNLEMNPIDLDAQEHIKHQRKKLRNRLAAQRCRKRKIEREETLKLKVKELKNKNSELTNLASKLRMQVCELKQQVMHHVNEGCQVFYKDADLDS

>ATF1/CREB_Hydvu ENA|HAAC01017767.1 TSA (PTHR22952:SF101, CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN B): Hydra vulgaris, contig CUFF.S26829.1: 780, 3, 783 (+) CREB alpha isoform MELARHSFQQPLNVAPSLSNVNKTSVVLQQQSVIQSNQHQLQHQLQNMHDGGIEGKRREILARRPSYRRILDDLAGDGPVKMENYDDTGSSGESSPNGNNEEDINGINQNAIHQEKQYQNIHLNGIVSSVQGGENSMNQLHDSQPGDNQYIITTQGPDNKIQAYTIKGTLPMGLDNTSLASPHQLAEEATRKRELRLYKNREAARECRRKKKEYVKCLENRVAVLENQNKALIEELKSLKDLYCSKGD

>ATF2_Hydvu ENA|HAAC01028898.1 TSA (PTHR19304:SF10, CYCLIC AMP-DEPENDENT TRANSCRIPTION FACTOR ATF-7, PTHR searched manually): Hydra vulgaris, contig meta_rep_c20237: 1635, 3, 1638 (+); identical to gi|449665335|ref|XP_002159178.2|; identical to ENA|HAAC01034356.1 from CFANSDH up to CSPSSITMEKPFKCTKCSQCFANSDHLAVHKCQLHVKIPSVLFQPGSDQTPTPTRFMRTADAVDSQLFEEINPFDQDFSIASKNQLSSEANNEDISSTTLKQHKGPLQTPNPIITSHNFTSVSSLTAFPSSKKPSVLIKNEEECVTADKKSSSKSILTNENIKNQENQSFLVHQEYQDLCLPKQLDRSEFSEQRDSHSLSVFSLLQQQINIQCSPSSITEQSNTSAQLNQHTSSTEVLRDHLNKLIKSGQIKIQFSSSPSSTKVQATIVGTIAXKQSGTQSAVIQSSVNPIILSSLASTVATPSIRNIAPSTNPFDSSVGSGVAKQKLRQVVQQSTFSSMDNNNSNNVISQRISISPSNQGKYKDIILEDEDSMKEGSESGGGKRRGRTSEELTPDEKRKKFLERNRAAASRCRQKRKVWVNQLEKKSDDLMQTNAELMNEINSLRSEVAQLKALLLAHKECPVTLHQKSVLERISSGVAYVTVSDGQIIAIHPINELNGENEITSAEELASSALTNMGSISSNQP

>ATF3l1_Hydvu 1017471 ENA|HAAC01017471.1 TSA (PTHR23351, FOS TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, contig CUFF.S18738.2: 444, 3, 447 (+); identical to XP_004208997.1 from FIKLEEGER up to the end STHFFNEPECRLLQTDLNHPVGGYSLDQLAPNYDISHHFPQIKRENHISFGDQDNVSLYFSDRKDDFIKLEEGERKKMRRERNKVAASKCRNKRKEHIKCLMKESDDMENKNVDLQTEISSLQAEIRELECILDSHTCIMKSKTKRGE

>ATF3l2_Hydvu ENA|HAAC01007940.1 TSA (PTHR23351:SF26, A3-3): Hydra vulgaris, contig asmbl_43141_ext: 444, 236, 680 (+) identical to gi|449662248|ref|XP_004205502.1| PREDICTED: transcription factor kayak-like [Hydra vulgaris]MDFSFYSQQGVLGSLPEDKRNYVPIDNNFEIGDLPVKLELRYAIEAKRAEKGLDMPVIEKLPRVSRELTMEEEERRRVRRERNKVAALRCRVKRKSHVTKLIEETDDLHKANNQLENIIERLELEKHKLEEAIRLHSCKSIKLCGYDK

>ATF4l_Hydvu 1044351 ENA|HAAC01044351.1 TSA (no PTHR): Hydra vulgaris, contig miradenovo_rep_c81353: 1050, 147, 1197 (+) ATF4/5 Low conservation in the bZIP domain; identical to XP_002160144.1MIKSDQQDLLYCSNEDAFNFYGNGDGLSNHDESIYDKSSFTTKFHILSTALDFQWVYTENDVIKNDFGNFENAKNQLSSNITFQDFIECEESLSSDYLVNDMFDFGLSSSPESSTSDEWVENTTCISLLSDKIDRSFVVLENREIISSLPIKEEYTVPECSFIDISSPVSDDSISEDDFSGNASILISELLGLDQNLLPNKNTNFNVFNANIINENEILKSSFSDGDCVGKKLSSENIQSDYNERYFKASCVSNENLWQIESNYNKSSPFKKSLKTTEQKLRKRVQNRKAASRYRDRRKYVLDDIFNGAADLEKQNNDLKGKVLSLQHEINYLKNLMLDVIKARLSNKAC

>ATF6_Hydvu 1010821 ENA|HAAC01010821.1 TSA (PTHR22952:SF93, ATF6 ISOFORM C): Hydra vulgaris, contig CUFF.12714.1: 1161, 27, 1188 (+); identical to ATF6_Hydvu gi|449671423|ref|XP_002154408.2| PREDICTED but missing the N moietyMRMIKNRESACLSRQRKKEHIKTLESRVSAITEVNQQLKEENCILKQRVQELENENELLRNRGMLKSGVKRSSAMLSLLLFYYFNPLGLFNVNQVLPGQPVQSLLPMHRSRTLLQFDNSNTLNFFPPLESYDEKEKARNSKIIQLNENIFHNAKNVDEEFKAQLSFSVNKKEVTNKLLKKIQTVKKKPSVTLHETEADCGEHFNETDVNRITESLEQLVHSSTIKKSNKIKNARHYPCYSTNIAARGKNLINNTGMSCNQTSPLTQSSYLKLLREKEKKRRDEYVMNNTSQELVNAIQKTIIRKADTFYLFTLKDYMMLPATNYSSIQRPKVTFMLPAYMAYSNINASNKNNTVVKMLQIDCHVIDTKLIDVGQDLLPKDLIPKLNS

>CREB3l1_Hydvu 1038572 ENA|HAAC01038572.1 ATF TSA (PTHR22952:SF96, CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN 3-LIKE PROTEIN 2): Hydra vulgaris, contig miradenovo_c44494: 1374, 84, 1458 (+); identical to ref|XP_002160519.2| CREB3l only conserved in the bZIP regionMMLDTEKMDVDLSIVKKERLELDDYGQNTGNILDNFITEHDYHDFPQSVPNVQCIGDDDVNVDWLSSFFDEPLHDHMSGLNPPLTDLVSISNSNSKLTFVSGENEDLCLDSMPIFSECYTNGVFNVSSKGSTTTSTSSPALRNFNPLLSQTKKETFTEDDFVKDDVKKGQILTKPQNFEVDKQITKTENQQKLFLFMNTPENRVKLAGTNFNIINANLLNKLSGQNNDKPMNVIQLKKCIKLNNVVKCNTTTTNSNASTVSSENKTLNTAPKIILNKNNGITDILQSSLLQGIIKKEPENIEIDSGYESPNSNESPCSPPGDIDKSSYDTYIDVPPHERQPFYLSEEEKRTLIIEGLPVPTSLPLNKMEERALKKVRRKIKNKISAQESRRKKKEYMEALEKRVDSFANENSSLKKKMSNLEVANRSLILQVQKLQALISGNSDSKQIPDIQSLETVP

>CREB3l3N_Hydvu ENA|HAAC01026119.1 ATF TSA (PTHR22952:SF105, CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN 3-LIKE PROTEIN 4): Hydra vulgaris, contig meta-ga_rep_c06677: 888, 1, 889 (+) CREB3-related identical to XP_002157513.2 from DPISNWE up to the end but 65 residues missing in the N-terminus ENA|HAAC01026119; related to RecName: Full=Cyclic AMP-responsive element-binding protein 3-like protein 4; Short=cAMP-responsive element-binding protein 3-like protein 4; Contains: RecName: Full=Processed cyclic AMP-responsive element-binding protein 3-like protein 4 Sequence ID: sp|Q08CW8.1|CR3L4_XENTR Length: 428DPISNWESNIERSIWGSILDDLPDEILSTEIDNHLNNFQNASRHENDIVLENVINSLDDESCLLTMCTKEILNNIETDENYDTKSQEKISQTSNDFNLSISNESDEVEKSVQLLPFLQNFLQNSSIKVGENVFFIQKNQVATSTPSASHYSDIAVQQVNISTPTVFSQKSSLQNLAGLSKTSTLNDKQNEILTSVSKIKNAKQPNNIEDHNYFNGVARDAIGTNSEKQVSMLKLTDEEKRLLELENVVLPENFGLTKDEEKILKKVRRKIKNKQSAMESRRRRKEYIDSLEQRCFS

>CREB3l3C_Hydvu ENA|HAAC01031606.1 ATF TSA (PTHR22952:SF96, CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN 3-LIKE PROTEIN 2): Hydra vulgaris, contig miradenovo_c03021: 1068, 3, 1071 (+) identical to XP_002157513.2 from SIKVGENV up to DEEKILKK, miss the N-terminus; CREB3l3SIKVGENVFFIQKNQVATSTPSASHYSDIAVQQVNISTPTVFSQKFSLQNLAGLSKTSTLNDKQNEILTSVSKIKNAKQPNNIEDHNYFNGVARDAIGTNSEKQESMLKLTDEEKRLLELENVVLPENFGLTKDEEKILKKVRRKIKNKQSAMESRRRRKEYIDSLEQRVKNCTDINLTLKKKVDSLTDENKSLLKQLKE

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LQKFFSTSVQQSHNTKKGTCFAVLALTFGLLFLPFNSMSGNILKSSTEVPNQANVFRSRTLLHLKKQNNYEAFENDAVLPHSDIYNRTYLTSDFKVFSEEMRNKIEQLLTEDSGSNLLKTTLDVYMNSIKLSRNWELKKLDPINVLEFHQDDVSSY

>Fral1_41771 Hydvu ENA|HAAC01041771.1 TSA (PTHR23351, FOS TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, contig miradenovo_rep_c64333: 810, 3, 813 (+); Fos-related antigen: Fra; identical to XP_002154763.1 (except few residues upstream the initiation codon) MNFLMHQEVPNQDFEHLDLFEEFSMYETPLPKFVVPNTFIKNLEEKKSCCFYENKANPIQSSLQVPYDNEFNSSLPQFHEAAFSSEMSYNSLNRSLVQGVSSNGRFSQSPVNSNYSISPLESPNHQFIPDVYLGYMNRNTTMSKYQDRNCCPYLYNGVLSERRTKRDEQLSYEEYEKRRLRRERNKEAALRCRTRRRERIDALEQETAGIERENLKVNDEIAKLEKQVNEMQKLLREHKCKKNLPYNDESLNLANVLS

>Fral2_Hydvu ENA|HAAC01007332.1 Fos TSA (PTHR23351, FOS TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, contig asmbl_40508: 573, 177, 750 (+) see shorter isoform 1041222 (different ATG, close to C-term, then extended C-term ?; identical to gi|221132540| ref |XP_002165663.1| PRED: transcription factor kayak-like [Hydra vulgaris] except 12 AAs N-term previously Kayakl1, transiently down-regulated by 3x at 2 hpa after mid-gastric bisectionMVMACLLDTPIMEENIPFKEIDHFLAEMASLDDDPLWDIDGYSAGSWHTDSDEELSDKKFEIYENSINEESVNLELNKEISSETSDMSDIFSLYTADLPNSPLLKTKKKKKSSRVRQKNETQILPKRERNKLAARRCRKKQKDRIEVLEKEVESIEHDNHEVLKEILALQSQLEELQQLLISHSCVAKEKL-

>Fral3_Hydvu ENA|HAAC01032370.1 TSA (no PTHR): Hydra vulgaris, contig miradenovo_c06757: 444, 124, 568 (+) partial?MSLLTTPVLEQKRFVDHVDYFSQYTDEDSSTSFEKNDSFTIDSVDKYLVKEIQIKFNKSSTSGKKNDNTLTYENSQSINLNEKRNRNRLAAQRCRQKQKERIQYLEKDAKRIEKENLHVELEIKELNYQLDEIKKILRYHCCRIIPTK

>Fral4_Hydvu ENA|HAAC01019888.1 TSA (no PTHR): Hydra vulgaris, contig isotig13448: 447, 3, 450 (-) partial?RYKQISIKFIIHLFEKMNEETGEKNTKSKLRNVLKAKLLSNDGFEDNEANKIDDTDSESCDSDNKANYKDASNTPLEERRIRNRLAARKCREKRKQRIWNLEKICSSLEERISALHKEIAGLDNQKSSLSKLLQNHACCRFVTSKNMFV

>Fral5_Hydvu ENA|HAAC01002706.1 TSA (PTHR23351, FOS TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, contig asmbl_21252: 501, 108, 609 (+) partial? see shorter isoform of 1033555 (different N-term ?); identical to ATF2l_Hydvu gi|449677282|ref|XP_002162229.2| MMKSMKMRMEILENDNSFVENYDDNVDVKEVIRCSIKNKHASFNSDILAEKEESEIEDCEDSDKTCSRRQNKKNSLEDEETLVARRERNRLAAQRCRQRRRDRIEKLEKICQRLECDGSSLENEISELQKEMSDLQQVLTNHKCHAKINTKFVTKSGNKTETYIPTL

>Orph1_Hydvu ENA|HAAC01035381 TSA (PTHR23351, FOS TRANSCRIPTION FACTOR-RELATED): Hydra vulgaris, identical to gi|449678082|ref|XP_004208996.1| PREDICTED: uncharacterized protein LOC101235870 [Hydra vulgaris] N-terminus identical to ENA|HAAC01002465, partial?MMDQILPGYAEECRLLQTDLNHPVGGYSLDQLAPNYDISHHFPQIKRENHISFGDQDNVSLYFSDRKDDFVRLIKLIDYLSLYSVLQPRQHNTFAQRWDKLGLMWYLSYRVISSLLSNDCAC

>Orph2_Hydvu ENA|HAAC01002465.1 TSA (no PTHR): Hydra vulgaris, contig asmbl_20189: 420, 100, 520 (+) partial? see isoform 1035381; contains the N-terminus of XP_004208996.1 up to DRKDDF; almost identical to ENA|HAAC01035381.1 TSA: Hydra vulgaris, contig miradenovo_c23899: 381, 107, 488 (+) slightly longer (15 AAs); N-terminus identical to XP_004208996.1MMDQILPGYAEECRLLQTDLNHPVGGYSLDQLAPNYDISHHFPQIKRENHISFGDQDNVSLYFSDRKDDFIKLEEGERKKMRRERNKVAASKCRNKRKEHIKCLMKESDDMENKNVDLQTEISSLQAEIRELECILDSHT

>Orph3_Hydvu ENA|HAAC01034003.1 TSA (no PTHR): Hydra vulgaris, contig miradenovo_c15049: 315, 1, 316 (+) partial?ISFVNFTNACLLFPPLFTLNIIARLQSWIFSFYSQQGVLGSLPEDKRNYVPIDNNFEIGDLPVKLELRYAIEAKRAEKGLDMPVIEKLPRVSRELTNRKKRNEEE

TRANSCRIPTION FACTORS (bZIP, C/EBP): CCAAT-Binding Protein (C/EBP)>C/EBP_Hydvu ENA|HAAC01031508.1 TSA (PTHR23334, CCAAT/ENHANCER BINDING PROTEIN): Hydra vulgaris, contig miradenovo_c02537: 906, 79, 985 (+); 99% identical to PREDICTED: uncharacterized protein LOC101237534 [Hydra vulgaris] Sequence ID: ref|XP_004209260.1| Length: 302; 53% identical 70% similar to CCAAT/enhancer-binding protein beta [Gallus gallus] Sequence ID: ref|NP_990584.1| Length: 328 in the DNA-binding domain from 33/236 to 112/314; Q05826 (CEBPB_CHICK) Important transcriptional activator regulating the expression of genes involved in immune and inflammatory responses. Binds to regulatory regions of several acute-phase and cytines genes and probably plays a role in the regulation of acute-phase reaction, inflammation and hemopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Functions in brown adipose tissue (BAT) differentiation. Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG). Binds to the MGF and MIM-1 promoters and activates the transcription of these genes.MDSNEDSGEHEIQSNENWYTTNAEIASQVISKYTGATSSSNKRKQTNTKPSDEEYSRKRARNNVAVKKSREKAKNRIVETQVRVEQLSQENEELQTKVTLLTKELNVLRALFTNGGFALPGELQIVSNNSNNELSQNQHQNNEQSTSNGGNHNLLNKEVKMSFDTKIRPLKPMPRVFTNSQKSLLSSSQQSSDSFNPYERNNESQLFTYNPKYTPATEYVKKETKKSNCHTILVSPDTTPQRSSSLLYQNGAEMRHTSVIQTVTSQPQQQQKSSLTQNSLGKFCIIQDPEKVGQVKIVPLDS

TRANSCRIPTION FACTORS (bZIP, CNC): Nuclear Factor Erythroid 2-related Factor (NFE2-RF, Nrf2)>Nrf1a_Hydvu ENA|HAAC01026198.1 TSA (PTHR24411:SF25, SUBFAMILY NOT NAMED): Hydra vulgaris, contig meta-ga_rep_c06923: 1728, 3, 1731 (+); 100% identical to PREDICTED: uncharacterized protein LOC100209530 [Hydra vulgaris] Sequence ID: ref|XP_002160548.1|Length: 535; Uniprot Q14494 (NF2L1_HUMAN) Nuclear factor erythroid 2-related factor 1, Activates erythroid-specific, globin gene expression MIWDQGVSNFIVALLFTKWILQSSNDTLQINQIFNNVPFNKRLVSTFRNLYKNAENTQLDLNIAGYHDLQNLKGSNVYSYEVQNLLSWQNAYHRGDLRLHSELQLSILPVNAVHKGDKKISNSLQTISNVFIDDGYDSSGLSLDSPTSSTLSETRPDYLFSSSSPPFSDNNFENFSSLPGAYSADFDIDDLLDNNDLNLGVETNYKSQSCCNEKEKLSCLNPFSKILDIDHDLDYVSSPLKSPSFDEFLTSPNQGFLTKYGIDISFEDPFEICFTNSSLKEKLLDSSLNIEDYDINELKLEEDVDRALVESLSPNVSKYKVMNDESNEVSKALIEKNAFEVDHDYYQRSDSSLNYTTKSYLNDVAVGARQLTELSHTFAPSHSVTNSKETKSENIWPDFPYTSEELVTMPVDTFNEVIKLLDEIRKHIAKDVRRKGKNKFAARGCRKRKNDLIKCLDIGVDELIRKKNNLLDERNKIIAETLEIRRKTMWLNSYIFMHLRDSNGGLYSSVDYSLQYTSDGNVYIVPSDKTSKVHI

>Nrf1b_Hydvu ENA|HAAC01041538.1 TSA (PTHR24411:SF25, SUBFAMILY NOT NAMED): Hydra vulgaris, contig miradenovo_rep_c62116; short isoform of NFE2L1a, 29 last residues unrelatedMNDESNEVSKALIEKNAFEVDHDYYQRSDSSLNYTTKSYLNDVAVGARQLTELSRTFAPSHSVTNSKETKSENIWPDFPYTSEELVTMPVDTFNEVIKLLDEIRKHIAKDVRRKGKNKFAARGCRKRKNDLIKCLDIGVDELIRKKNNLLDERNKIIAETLEIRRKTMWLNSYIFMHLRDSNGGLYSSVDYSLQYTSDGNVYIVLNDKMSKVINKFQKINFYYYKMFKDPVVF

20



TRANSCRIPTION FACTORS (REL-like domain): NF-AT5, NFkB>NF-AT5l2b_Hydvu ENA|HAAC01010118.1 TSA Hydra vulgaris, contig CUFF.11309.1 : Location:1..359 (PTHR12533:SF7, NUCLEAR FACTOR OF ACTIVATED T-CELLS 5)HXARNWEADKELQDRGIEPVTWKTKKKEAKLAFQVSISSISTHSGYQFICYSRLFQCTAPSGNPEIYWSSHTEGSPVGGLEMGFHGKKFASGFKIRFFSKESSHDPPWETYAVVDRNKSNL

>NFkB_Hydvu ENA|HAAC01031114_1 (PTHR24169:SF0, NUCLEAR FACTOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B-CELLS 2, P49/P100): HyNF-kappaB, partial, 338 AAs, partial (N-terminus missing), 99% identical to nuclear factor of kappa light polypeptide enhancer in B-cells [Hydra vulgaris] Sequence ID: ref|NP_001267795.1| Length: 477 Number of Matches: 1; 39% identical, 56% similar to nuclear factor NF-kappa-B p100 subunit [Danio rerio] Sequence ID: ref|NP_001001840.2| Length: 902 Number of Matches: 1EYLKKYNSINPPIDVETFVKRLEDREDKKLINRLTGVECNNKDLQSEASSLMKDLNVHSVVLAFHCFLEDSNGRYTINLPTVYSVPIYDGKNKKGCEYKILRLSSVSGTPKGGEEVWMLCDKFDKSDVEVRFFDDTPVVPWSALAIVNKSDVYNQNLIIFRTPPYKHKVLDQPVKVKIELRAASDHMRCSKHFDYTYNNSSDDGYEVGKKRKKTTPAIPDFDVAQLKYFSPQEQLNQLFSDEQNLIQSHVAYNNFPQPVLPVVDDTFNIHMINGFSTDFNSTHSYFPDDMLCVINQVANINTSELCNEKEINVDEVKLDEIKVYDKEEDDNNLTFPLT

>NFkBa_Hydvu ENA|HAAC01034681_1 (PTHR24169:SF0, NUCLEAR FACTOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B-CELLS 2, P49/P100): HyNF-kappaB, partial, 102 AAs, partial, N-terminusMMFDPEIFGISHSGPYLKIERQPRKYGYRFRYKTEGVCHGGILADTDGAVNCGSSKSCPKIKVHNLNGQRAKVVLRLAAEHDNETMHIHSLVYNKTVTNGVR

TRANSCRIPTION CO-REGULATORS or MODULATORS: ECD/SGT1, IkB, IRF2BP, KEAP1, LITAFs>ECD_Hydvu ENA|HAAC01032499.1 TSA: Hydra vulgaris, contig miradenovo_c07395 (no PTHR) SGT1 family; 97% identical 98% similar to ecdysoneless homolog [Hydra vulgaris] Sequence ID: ref|NP_001267880.1| Length: 598 Number of Matches: 1; 36% identical, 55% similar to ecdysoneless homolog [Gallus gallus] Sequence ID: ref|NP_001186453.1|Length: 638 Number of Matches: 1 (7/14 -> 602/626); O95905 (SGT1_HUMAN) Novel regulator of p53 stability and function. May also be a transcriptional activator required for the expression of glycolytic genes. Interacts with TP53 and MDM2. Transcription co-activator. Belongs to the SGT1 family. MSSDIIVEYRIFHLNDDVLKIVRNYYDDLINSVAKEYIWQKESFRLSSVEEYSGLACLSGSTCVGENINDEWFIVYLLFEISKHHKDVIIQVNDNDGDFLLIEAADFLPPWLTPANSENRVFIKDGKMHFIPIPSNPAIHIPSNPAEIMVNFNSTPTLKQAYHLLTSSLKTVANENVQCAIQKRISCYPSKFMKEFHHALCYIPVEIVYILQKKPKLVSSAVQAFYERDSSDIKTCRSMSSFKPESRTLVLVRFTRHLYCQLMQAHFVPEQNSLWKLPAVSNSLRKPAELGFKLTCGFQILLSRLNAADSKDNTNKAPSLSEPSGKMWEQYLLNLNNSNYFKNELEGSVKYKDLMNKAKLHFQDHVANSYKSDTIGLLIQDLIHESGQYISDIKPACENVGLEDDDSWMTLTEEELDNMMLNMWGKNHPDTKKHTENLNTLVTNMKSFVEQVSSYEGAEPLNNDYKGAEPLNSDLKQNDKDKVLDPIHFEPDIFMKTIKNLLDSSSDTNKQDMSDDDEENDSDSDLDSEMVEVMQQMDNELRTTNIPKSFDCKEEKFGLNEEIMNIDINLVKNFLESFSSQEGLSGPVSNILQSIGMSLPPNDYEM

>IkBl_Hydvu ENA|HAAC01007824.1 TSA Hydra vulgaris, contig asmbl_42641_ext (PTHR15263, I-KAPPA-B-LIKE PROTEIN (IKBL), 355 AAsMSRLKKIKKKLHRYISSGRIKAINKLFRDNCDVAEHLRSEINFPYKKNKWYLHKYCAKGESSMVRVLYNAGADLSICNKDGSNSLHIALNYAIDNFDQDFFYDIVTELFNNASEELRTKKNRYGETANELFDEIVDLLISKQSRTLIESDDEDVEDCDWNGKLFFELGEENFVNEAYTDLEYADTYQKEKAESFSEWGDRIRKEYNIKNKNEKVKTLPSVKRKKVESSNLTFVLKKKLNIFNLRETYEEKCNRIFGKEYNSELDFKKVPWPIRNSELVYQNFNSHADEMIENLTYGFTSEDKIKYLKKQQIRWHPDRFLQKCGHRLNVTDKDNILKCVQHLSQKINAVVNCSKH*

>IRF2BPl_Hydvu ENA|HAAC01000847.1 TSA: Hydra vulgaris, contig asmbl_13301_ext: 2073, 3, 2076 (+) 691 residues (PTHR10816:SF14, INTERFERON REGULATORY FACTOR 2-BINDING PROTEIN-LIKE); isoform of TR:T2M679_HYDVU Interferon regulatory factor 2-binding protein like; Q8IU81 (I2BP1_HUMAN) 39% identical (169/438), 53% similar, acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities. May act as an E3 ligase towards JDP2, enhancing its polyubiquitination. Represses ATF2-dependent transcriptional activation.SCSFDNSRLITNNKSFKHKGESEAQKTIKIVVIFFWNALFWLHFKFKLLANIYMEYLYWTKNMSTTRFQRQQCYLCDCPRAPWAILNDFSEPICRGCCNYEGPERIETVIDYVRSLRKGWDQQVRALKPNMNSTGTSIGSTPSPSGHSNGSMETNVSIANNAYSFSQYNGMPQQLDHFRFLHNVKSEHHVPPENHVGENFNQKNVFAVPNESSINQTSQIAPLSSRNADDTHDEHRRFLTSLAVNNTKDNHVRVPIIHRPEYSEYPDIVRETLEVLNSCVPFDIRFKKDHNHIGRVFLFEAAPRAGTTSPNEFELKIHIEYPRGSENFCQSASSVAKQMYQDSMKDYSRGLSSGFKYLEYEIHGNEWRLLGDLLPEQIRIFKEPIGRVFLPMRLIDYPIFHSMLGPPLPGSSKYRPKRKADDVEVIGAPSRAPRRTYKEREDEQIQRHLWMQSQVDALRLSMAHLTGTPEDAIHLNSIRSGNMLDLHHHTTPHTPLTPHTPLTPNSQNLGAPHQPSPKPWGVSASMAALISAASAETNGNSKEPRKLLPESSKSKSPLHEKSPHHEKEILEIKDNLKSEEINEHKEDNLNKKANMKNASKIKCSICEDWLDDSHFVQCPSVPAHKFCFPCSKDSIKKQGFGSDVFCPSGKQCPLIGNNLPWAFMQSEIQTILATKPRSRVSLKEESIEDKS

>Keap1_Hydvu ENA|HAAC01013081 TSA Hydra vulgaris, contig CUFF.17728.2, 98% identical to HAAD01003878 TSA: Hydra vulgaris, contig Seq03878, Kelch-like ECH-associated protein 1 (KEAP1) assembled mRNA contig; 99% identical to gi|449663402|ref|XP_002157473.2| PREDICTED: kelch-like ECH-associated protein 1-like [Hydra vulgaris] (seq76157_loc24953_vl0056310)MSTECHETCFDISEQHHKLVFLKLPLLKKDKFLCDTTLVVGRKKIYAHKILLACSVPYFYSMFNHDVVESRQNVITLKDLDPESVESIIDFVYTSKIVITQRNVQAILQVATMFQINLIQEKCCDFLESQLHPSNGLGIYLFAELYGCSKLKSRAKTYCNWHFSDVVREDEFLNLSLEQVKWFLNQDELCVRSETEVFNAAIRWVSQNSQQRKKDLQYLLPLVRFNFLPKSFLSLQLETNDLIMDDEFSLKLLFDALNDIEVKQLVATKRKPIGNNVVFYMGGYNRKSFASYGYFNPETETWFKLGDMCSPRSGAGCVSLGGLIYMVGGRTNSLQGKSDSNSVECYDPYSQEWKNIASLNSSRHRLGVAAVDGVIYAFGGSDGMVHLNTVEKYDSEKNLWEPAPSMNTPRIGVGGTVLNGVIYAVGGFDSENRLQTVESYMVGESSWKFLASLNTPRSGAGVTSMNGHVYAVGGYNGVAQLNSVERYCPYENRWTNISSMNERRSALSVAVVRNKLFAFGGYDGERFLDSVEVYDPDNGEWQLLNPMPDARSGAGVAVCIAPII-

>LITAFl1_Hydvu ENA|HAAC01024147.1 TSA Hydra vulgaris, contig meta-ga_c01158 (PTHR23292, LIPOPOLYSACCHARIDE-INDUCED TRANSCRIPTION FACTOR REGULATING TUMOR NECROSIS FACTOR ALPHA): LPS-induced TF regulating TNFa (LITAF, PTHR23292)LVEQTKQRSKLAPAEESSSRENSKLELEKKNPSWPTHIDKLILDGQKHSNKRTCQSKNLEKTDQDQQALHEEQDNTVQSINLIQNRKSTPCRQTLSSQELTTNKYEKILQVWKIEKPVQSRSLLCEEQKSTIHSVKSIQENCVQSAQIDKCLAENEYSQLKSTIKPAIDSTTKPAINSITSKSKLIEDAKIVMHSKRKMSESYKAAPIISNEQRRYTQPALEFKTSSIRKKSLSEQCNQPIIEKPVTTNKVESDESPNNTAQRRLSKTELAKRERKISLQESQSIKNQVLNLEPEKFSQLFSYAQRRISDASPQMPGYPICDPKSSLLCESKIIEEQPSSLTESEFQKQAVMTLCEYCNYCILTKLEYHAGFHTCVWSGIICIATGFLCGFIPFCINECKDVVHKCPNCNKVLGTYRRL

>LITAFl2_Hydvu ENA|HAAC01017881.1 TSA Hydra vulgaris, contig CUFF.S29944.2 : Location:1..647 (PTHR23292, LIPOPOLYSACCHARIDE-INDUCED TRANSCRIPTION FACTOR REGULATING TUMOR NECROSIS FACTOR ALPHA): LPS-induced TF regulating TNFa (LITAF, PTHR23292)MFKEGNLPHPQSGVNEDQNPPQYQPSVNGYKNAQPQPYPYQTYQSEPYLKQSEVLNQQEYFPHNTTMYSPSPVYLTNVLYFSTCPMHVVCQHCRAQVLTSTMHTSGVAVWLISLLICILGGFLGCCLLPFCIDGLKDVEHLCPNCGKVCGVCRRL

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>LITAFl3_Hydvu ENA|HAAC01038429.1 TSA Hydra vulgaris, contig miradenovo_c43623 : Location:1..582 (PTHR23292, LIPOPOLYSACCHARIDE-INDUCED TRANSCRIPTION FACTOR REGULATING TUMOR NECROSIS FACTOR ALPHA): LPS-induced TF regulating TNFa (LITAF, PTHR23292)KNKIRAWIITQLEEIKSYVKYLRAIKMNPNEPPKYEESMINSQPPPNYTSNYPPPMQPGYYVPPGNVYPPPDQMHTKPMQQPMYPPGPATNIVVQPQVAAAYVIAFNMAPIRMQCPHCQAQIVTSIEYVSGLLAWLLCLGMFFFGAWLCCFIPFCVDGCKDVNHSCPNCMKVIGTFKRM

Transposases: HARB like>HARBl1a_Hydvu ENA|HAAC01038899.1 (no PTHR): 477 AAs, Blastp: SEVERAL Hydra Hits @ NCBI, uncharacterized protein LOC100199123 [Hydra vulgaris] Sequence ID: ref|XP_002158178.2| Length: 521, Number of Matches: 2: 1/1->144/144: 98% and 208/145-> 446/383: 98%, no match between 144 and 208; Myb-DNA binding domain / GT1 superfamily (N-term) and DDE-4 endonuclease family (C-term), Deltablast excluding cnidarians: from 263/67 -> 469/273 putative nuclease HARBI1-like [Amphimedon queenslandica] Sequence ID: ref|XP_003389956.1| Length: 418, 62% similar, 7e-52; also highly conserved in plants and bilaterians, Harbinger transposase, Sinzelle et al. PNAS 2008 MSQHSEKECIDASTTNIGLCTSPLNKFVWNMANTRVLLDLWKDNYNALTSARRNTNIYKQMAAEFSNTFNIVPPLTGYQIQSKISNLRKQFRREKLQVGSSGGAPSKWWPYDIVAKIIGGEASLDNDLLSQSQNFSTQDFQDGQVATMEDGKETVSILNIEALDDTSDVQSIVTIPDEEPTQSTSGCNKRRSSDDEKTLNKIAKTEPGDIGKGKSYWKNMESVLAVLRLRRRTLINDESITHPFSYLDLASFKLNQQGYLIERKVWVRPKSSQWFNEIFTQMEECEFKEHFRVNRNTFNFLVNELHPHLGKTTTTMREPISVVKRVAVALHYLASCEEYRVVSSLFGIGKSTANLIVHEFINAVNDILLPKYVKFPLSVENLNKHSRDFEAILGFPQCVGAVDGCHIPISAPKDQATSYYNYKGWYSIVLFAVVDSRYRFIYTSVGSPGRNNDSYILQNSSLKEILESNLFDKCCKX

>HARBl1b_Hydvu ENA|HAAC01025081.6 (no PTHR): uncharacterized protein LOC101238054 [Hydra vulgaris] Sequence ID: ref|XP_004209397.1|Length: 198 MREPISVVKRVAVALHYLASCEEYRVVSSLFGIGKSTANLIVHEFINAVNDILLPKYVKFPLSVENLNKHSRDFEAILGFPQCVGAVDGCHIPISAPKDQAISYYNYKRWYSIVLFAVVDCRYRFIYTSVGSPGRNNDSYILQNSSLKAILESSLFDKCCKELGDSLVPLCLIGDSAFPLTRHLLKPYPKNLELSEI*

>HARBl1c_Hydvu ENA|HAAC01007640.3 (no PTHR): uncharacterized protein LOC101241637 [Hydra vulgaris] Sequence ID: ref|XP_004205687.1|Length: 231; Deltablast: DDE-4 endonuclease family, putative nuclease HARBI1-like [Amphimedon queenslandica] Sequence ID: ref|XP_003389956.1|Length: 418 2e -39SVVKRVAVALHYLASCEEYRGVSSLFGIGKSIANLIVHEFINAVNDILLPKYVKFPLSVENLIKHSRDFEAILGFQKCIGAVDGCHIPIFAPKDQAISYYNYKGWYSIVLFSVVDCRYRFIYTSVGSPGRNNDSYIFQNSSLKAILESSLFDKCCKELGDSLVPLCLIGDSAFPLTRHLLKPYPKNLELSEI*

Various proteins: ankyrin repeat, 2M protease inhibitor>ANK1_Hydvu ENA|HAAC01009865.rev3 (Ankyrin_rp, no PTHR) 270 AAs Deltablast besthit: ankyrin [Sulfolobus islandicus Y.N.15.51] Sequence ID: ref|YP_002840971.1|Length: 359 Number of Matches: 4: 50% similar, 5e-63; Deltablast on Deuterostomes: ankyrin repeat domain-containing protein 50-like [Strongylocentrotus purpuratus] Sequence ID: ref|XP_001195153.2|Length: 941 Number of Matches: 9; 2e-55; Deltablast on cnidarians: no strong hit! ankyrin-1-like, partial [Hydra vulgaris] ref|XP_002170883.2|Length: 897 Number of Matches: 12; 44% similar 2e-48 MDVLKAIRKNDVKKLEKLLKKGFKPNSVLDEFDSNNQLKYSTIPLSLAAKEGYTDIVSLLVKYGANLHASNDDWEAPMHIAAFYGHVDVMRFLLTRDININKQDKKGNTVLHVAVMKSQFNIVNLLLTNDTGIDINIKNIESKTALDIAKKERVCHIIDLIEEKIKQDMVNKNKDSAVVNPAPAFNSVIKAVPAFQTMKPQNKSFFESDVIIKEQEKQQLVRALSEIEKKEQSEKEKIKDLQAIDSLLDSLQCFDNNS

>a2M_Hydvu |ENA|HAAC01041815.1 TSA: Hydra vulgaris, contig miradenovo_rep_c65058 (partial); 94% identical to PREDICTED: alpha-1-macroglobulin-like, partial [Hydra vulgaris] Sequence ID: ref|XP_002170682.2|Length: 638 Number of Matches: 1; PREDICTED: alpha-1-macroglobulin-like, partial [Hydra vulgaris]Sequence ID: ref|XP_002170173.2|Length: 252; Predicted C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8-like, partial [Hydra vulgaris] Sequence ID:ref|XP_002159228.1|Length: 314; alpha-2-macroglobulin [Haliplanella lineata] Sequence ID: dbj|BAJ05271.1|Length: 1672; BLASTp besthit against human: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8 or KIAA1283, Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family. PZP: Pregnancy Zone ProteinTLKDSSNEKIYLSKIFDVKPEILNTLPLYIDHDAPSSLKLTLEGRGVIRNRVWVFKNETNYISVSKLGLNVLIQTDKPVYKPGQTIKCRVVVVNAELKPHKGKLKVVIENPSGTRMQQWNDVELNDGFASFELPTSEKPVMGIWKIRAEIDGYSATLEVEVKEYVLPQFQVTVKPPGFISKDMDEISTEVCAKYSYGKSVVGVMTAQVCQNKDYFNKQDYCLQVVKKIDGCATFKTSMRSLVKSLTQWYYPTISFNAQVKEEATGISLNSSVETVSVVNNPIKLTFEGSDVFKPGFPITVKLLASYIDNTPAGSILVNISAGTTGYSSSDLLNGVFEVKGGFLNVVLPDIPFNAQSINLLAIYERPKIVNSDESDWERQSSASKSIDAWYSPSHSYLFIEKPKTAVKNGTIATVLVHYTSVDTVPKKRTV YYSLVCTGNIRASGYKNIKFVAATSTTKVQSQTTTTAQPTTTTTTTTTKKNADLFLTIQM

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Supplement 4

Supplement 4: Phylogenetic analysis of the Arminin gene families identified in Hydra Arminin related DNA sequences from Hydra magnipapillata (Hydma) and Hydra vulgaris (Hydvu) were aligned with MUSCLE and phylogenetic tree was built with PhyML 3.0 using default threshold values (Guindon et al. 2010). Bootstrap values obtained after 100 trees are indicated at relevant nodes. Asterisks (*) indicate sequences that can be retrieved from ENA with accession HAAC010xxxxx.

Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O: New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Systematic biology 2010, 59(3):307-321.

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https://www.ebi.ac.uk/Tools/msa/muscle/

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2014_Wenger Seminars in Immunology Supplt1 Supplt3 Supplt4