UNC-54Caenorhabditis elegans genome

Chris Weaver | Bioinformatics | Spring 2008

INTRODUCTION• Uncoordinated protein 54

• Also known as: myo-4 (Myosin-4)

• UNC-54 is required for locomotion and egg-laying

• Gene: F11C3.3

• Transcripts: F11C3.3.1, F11C3.3.2, F11C3.3.3

• Wormbase ID: WBGene00006789

CHARACTERISTICS• Size

– 1963 amino acids

– 5892 base pairs

– mRNA sequence: 6826 bps

• Exons: 11

• Introns: 10

• Location– Chromosome I at location 14,852,479-14,863,527.

(2)

– The start of this gene is located in Superlink Chromosome I. (2)

FUN FACTS• Encodes a muscle myosin class II heavy chain (MHC

B)– Motor Protein responsible for actin-based mobility

– C. Elegan sperm is thought to be the only eukaryotic cell without G-actin. (4)

• UNC-54 is a thick filament component that is expressed in multiple muscle cell classes including body wall, intestinal, anal depressor, and sphincter muscles as well as sex-specific muscles

• Interacts with ITR-1, an IP3 receptor, and this interaction may provide a link between calcium signaling and the muscle cytoskeleton

GENE ONTOLOGY• Biological Processes

– Body morphogenesis, inositol lipid-mediated signaling, locomotion, muscle contraction (5), muscle thick filament assembly, Oviposition, pharyngeal pumping, positive regulation of locomotion, signal transduction

• Cellular component

– Intracellular, Muscle myosin complex, Myosin complex

• Molecular function

– ATP binding, Motor activity, Nucleotide binding, Structural constituent of muscle

PREDICTED EXON STRUCTURE

NOTE: Transcript is on (-) strand.

DISCOVERY• Origin: Welcome Trust Sanger Institute,

Cambridge UK

– Predicted coding sequence & Curated

• MacLeod AR, Waterston RH, Brenner S.

– Genetic screening (3)

• Partially Confirmed with cDNA evidence

MATCHING CDNA

yk1680h07.5 yk310a10.3 yk309c12.5 yk580g9.3 yk544a4.3 yk884b09.3 yk1236h10.5 yk243h10.5 yk1451d12.5 yk202c10.5 yk398h3.3 yk1264g12.5 yk777f01.3 yk548e5.3 yk1344a01.5 yk1454g09.3 EC016661 EC034441 yk1343e09.3 yk222b5.3 yk261b1.3 yk209h4.3 yk1523a04.3 yk557b3.5 yk453b9.3 yk1744g04.5 yk232b12.3 yk844b06.5 yk1028d10.3 yk310a6.3 yk1032b10.5 yk793c01.5 yk263g4.3 yk408h3.3 yk275a6.3 yk889a12.5 yk557b3.3 yk1345h09.3 yk253e12.5 yk437e5.5 yk1352e07.3 yk1318b10.5 yk310g12.5 yk1504c11.5 yk248d11.3 yk577h6.3 yk1548g01.3 yk395g9.5 yk1304a01.5 yk1255a07.3 yk1045f09.5 yk355a2.3 yk370g2.3 yk202c10.3 yk843b11.3 yk395e2.3 yk583d10.5 yk1023h03.3 yk1688b01.3 yk1264g12.3 yk560b5.5 yk1050c08.5 yk408d8.3 yk1454g09.5 yk583d10.3 yk383a2.3 yk542g8.5 yk1237e05.3 yk356b9.5 yk1438h09.3 yk209d8.3 yk1058h02.5 yk262e2.5 yk224a9.3 yk304d6.3 yk226b9.3 yk539h9.5 yk544a4.5 yk795a04.5 yk308a3.5 yk270c10.5 yk549b4.3 yk581e5.5 yk1181b07.3 EC013519 yk1079g10.3 yk794b01.3 yk1704c10.3 yk1134e11.5 yk383d7.5 yk280a9.5 yk1032b10.3 yk263g4.5 yk1034f03.3 yk777f01.5 yk1149d01.3 yk548b4.3 yk1195h04.5 yk1535a07.5 yk1045h03.5 yk1535a07.3 yk1157d09.3 yk232b12.5 yk1688b01.5 yk1166a08.5 yk1250g08.5 yk323d4.3 yk540g10.5 yk275a6.5 yk1218b11.3 CK590205 yk1295d01.5 yk1751f09.3 yk1278c06.3 yk309c12.3 yk261b1.5 yk1181d08.3 yk1216e01.5 yk367b7.5 yk578g12.3 yk1196h11.5 yk446f6.5 yk442b9.3 yk353b3.5 yk1276d04.3 yk1096a07.5 yk303h6.3 yk549g4.5 yk355a2.5 yk1045f09.3 yk1082h02.3 yk1181b07.5 yk1557e09.3 yk1112f01.5 yk272c3.5 yk1318b10.3 yk304d6.5 yk299h3.5 yk833c02.3 yk383a2.5 EC018158 yk1261d07.3 yk1218b11.5 yk1274g08.3 yk356b9.3 yk1182d05.3 yk1035b03.3 yk1304a01.3 yk542g8.3 yk443g8.5 yk1324g02.5 yk1186d12.5 yk549b4.5 yk339h2.3 yk1450a01.5 yk436e4.3 yk383d7.3 CEESJ01F yk1344a01.3 yk1079g10.5 EB996275 yk398g10.5 yk308a6.5 yk1680h07.3 yk1021b11.3 yk411e6.5 yk352g3.5 yk1033a07.3 yk544c3.5 yk1751f09.5 yk1444f05.5 yk272c3.3 yk364h10.5 yk1216e01.3 yk1274g08.5 yk1181d08.5 yk308g4.5 yk224a9.5 yk323d4.5 yk1749d07.5 yk1182d05.5 yk235f9.3 yk1266b10.3 yk1311b12.5 yk1165g07.3 yk1198f09.5 yk1354e10.3 yk1482d06.5 yk219e9.3 yk263d10.5 yk1548g01.5 yk1021a06.3 yk1278c06.5 yk367b7.3 yk205b2.3 yk856a10.3 yk549b6.5 yk1096a07.3 yk310a6.5 yk437g9.5 yk884b09.5 yk1166a08.3 yk856a10.5 yk353b3.3 yk1345h09.5 yk1276d04.5 yk1677e07.3 yk1034f03.5 yk365a4.3 yk1324g02.3 yk299h3.3 yk1247f03.5 yk559g9.3 yk1237e05.5 yk540g10.3 yk1033a07.5 yk1148d09.3 yk606h5.5 yk364h10.3 yk301g9.5 EC025822 yk446f6.3 yk1329e10.5 yk1561e11.3 yk1045h03.3 yk240f10.5 yk222b5.5 yk1438h09.5 yk540g8.5 yk398h3.5 yk250d9.3 yk1381g06.3 yk339h2.5 yk295b6.3 yk303c6.5 yk1557e09.5 yk1082h02.5 yk1025e11.3 yk396d2.3 yk407e12.5 yk1106d12.5 yk1381g06.5 yk1427g06.5 yk436e4.5 yk833e02.3 yk1214c01.3 yk1157d09.5 EC014277 yk250b12.3 yk1352e07.5 yk1482d06.3 EC005691 yk301g9.3 yk1035b03.5 yk1372b10.5 yk1451d12.3 yk577h6.5 yk544c3.3 yk1285h08.5 yk1753h05.3 yk260c4.5 yk874f11.3 yk443g8.3 yk1186d12.3 yk388h11.5 yk307c8.5 yk826f06.5 yk459b9.5 yk1225g12.5 yk321a9.3 EB998836 yk303h6.5 CK579866 yk1198f09.3 yk310g12.3 yk453b9.5 yk548b4.5 yk437g9.3 yk410g11.5 yk1677e07.5 yk408h3.5 EC038579 yk235f9.5 yk365a4.5 yk1744g04.3 yk1266c01.5 yk1749d07.3 yk1025e11.5 CESAB82R EC006171 yk889a12.3 yk219e9.5 yk209h4.5 yk1059f12.5 yk539h9.3 yk398g10.3 yk310a10.5 yk1450a01.3 yk205b2.5 yk1021a06.5 yk606h5.3 EC002296 yk1261d07.5 yk844b06.3 yk1354e10.5 yk540g8.3 yk1225g12.3 yk1255a07.5 yk270c10.3 yk1164c08.3 yk1087e10.3 yk454c12.5 yk843b11.5 yk1106d12.3 yk1149d01.5 yk260c4.3 yk232a9.3 yk559g9.5 yk395b10.5 yk262f2.5 yk1028d10.5 yk1677h12.5 yk1266c01.3 yk1050c08.3 EC014783 yk1427g06.3 yk208b8.3 EC002283 yk1285h08.3 yk1148d09.5 yk303c6.3 yk801f09.3 yk1444f05.3 yk250d9.5 yk1561e11.5 yk1753h05.5 yk1023h03.5 yk574a11.5 yk442b9.5 yk581e5.3 yk307c8.3 yk1343e09.5 yk395e2.5 yk794b01.5 yk826f06.3 yk1034a05.3 yk253e12.3 yk209d8.5 yk261h9.3 yk1214c01.5 yk1260e04.3 RST3_378411 yk1058h02.3 yk262e2.3 yk793c01.5 yk1237e05.3 yk232b12.5 yk833c02.3 yk1274g08.5 yk299h3.3 yk1157d09.5 yk235f9.5 yk395b10.5 RST5_372710 yk263g4.3 yk356b9.5 yk 1688b01.5 yk383a2.5 yk1181d08.5 yk1247f03.5 EC014277 yk365a4.5 yk262f2.5 yk408h3.3 yk1438h09.3 yk1166a08.5 EC01815 yk308g4.5 yk559g9.3 yk250b12.3 yk1744g04.3 yk1028d10.5 yk275a6.3 yk209d8.3 yk1250g08.5 yk1261d07.3 yk224a9.5 yk1237e05.5 yk1352e07.5 yk1266c01.5 yk1677h12.5 yk889a12.5 yk1058h02.5 yk323d4.3 yk1218b11.5 yk323d4.5 yk540g10.3 yk1482d06.3 yk1749d07.3 yk1266c01.3

cDNA/EST: 356

MUTATIONS (ALLELES)• 227 found so far

• Many do not have molecular information available

• e190 – Paralyzed

– No eggs laid, only larvae

– Defect in body muscle cells

– Body wall muscle development abnormal

BLAST MATCHES

BLAST MATCHES – UP CLOSESpecies Description Blast E-

Value% Length

D. melanogaster

Flybase gene name is Mhc-PI

0 99.4%

C.Carpio Myosin heavy chain 0 98.2%

H. Sapiens Myosin-3 0 98.2%

R. norvegicus

Myosin-6 (Myosin heavy chain 6)

0 98.0%

S. cerevisiae

Type II myosin heavy chain, required for wild-type cytokinesis and cell separation

5.4e-218 96.7%

C. briggsae gene CBG19269 7.69e-116 68.5%

HOMOLOGS

Organism Hit Count Hit ORF

Staphylococcus aureus temperate phage phiSLT

1 bpphA:NP_075512.1

Staphylococcus aureus phage phi 12

1 bpphI:AAL82321.1

•Archaea – 11 •Bacteria – 58•Eukaryota – 110•Viruses – 2

Viruses:

PROTEIN - WP:CE09349• Motifs

• Myosin tail• Myosin head (motor domain)• Myosin N-terminal SH3-like domain

MOLECULAR FUNCTIONS• ATP binding

• Motor activity (6)

• Nucleotide binding

• Structural constituent of muscle

REFERENCES1. http://www.wormbase.org/db/gene/gene?

name=WBGene00006789

2. http://www.ensembl.org/Caenorhabditis_elegans/geneview?gene=F11C3.3

3. Splicing Removes the Caenorhabditis elegans Transposon Tc1 from Most Mutant Pre-mRNAs MOLECULAR AND CELLULAR BIOLOGY; ALICE M. RUSHFORTH† AND PHILIP ANDERSON; Jan. 1996, p. 422–429

4. http://en.wikipedia.org/wiki/Actin

5. Mutations in the unc-54 myosin heavy chain gene of caenorhabditis elegans that alter contractility but not muscle structure; Donald G. Moerman, Santiago Plurad, Robert H. Waterston and David L. Baillie; February 1982

6. http://www.wormbook.org (Genetic Suppression)

7. http://pfam.sanger.ac.uk/

SOMETHING COMPLETELY UNRELATED

• Head Transplants•Are possible•First successful transplant - Robert White, County Hospital in Cleveland, Ohio •http://www.youtube.com/watch?v=HwPBE7fXj4k

“When the surgery was complete and the monkey came out of the anesthetic it could move it's facial muscles, it could be fed and follow movements with it's eyes. Of course, with a severed spinal cord it was paralyzed from the neck down, but the operation had been a success” -unknown