SEM5_CAEEL
ID SEM5_CAEEL Reviewed; 228 AA.
AC P29355;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Sex muscle abnormal protein 5;
GN Name=sem-5; ORFNames=C14F5.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF PRO-49; GLU-90;
RP SER-91 AND GLY-201.
RX PubMed=1372395; DOI=10.1038/356340a0;
RA Clark S.G., Stern M.J., Horvitz H.R.;
RT "C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3
RT domains.";
RL Nature 356:340-344(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION.
RX PubMed=9073451; DOI=10.1006/dbio.1996.8473;
RA Chen E.B., Branda C.S., Stern M.J.;
RT "Genetic enhancers of sem-5 define components of the gonad-independent
RT guidance mechanism controlling sex myoblast migration in Caenorhabditis
RT elegans hermaphrodites.";
RL Dev. Biol. 182:88-100(1997).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ARG-87.
RX PubMed=11689700; DOI=10.1128/mcb.21.23.8104-8116.2001;
RA Schutzman J.L., Borland C.Z., Newman J.C., Robinson M.K., Kokel M.,
RA Stern M.J.;
RT "The Caenorhabditis elegans EGL-15 signaling pathway implicates a DOS-like
RT multisubstrate adaptor protein in fibroblast growth factor signal
RT transduction.";
RL Mol. Cell. Biol. 21:8104-8116(2001).
RN [5]
RP FUNCTION.
RX PubMed=12169634; DOI=10.1093/emboj/cdf430;
RA Hajnal A., Berset T.;
RT "The C.elegans MAPK phosphatase LIP-1 is required for the G(2)/M meiotic
RT arrest of developing oocytes.";
RL EMBO J. 21:4317-4326(2002).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF GLU-90.
RX PubMed=15990870; DOI=10.1038/sj.emboj.7600741;
RA Gottschalk A., Almedom R.B., Schedletzky T., Anderson S.D., Yates J.R. III,
RA Schafer W.R.;
RT "Identification and characterization of novel nicotinic receptor-associated
RT proteins in Caenorhabditis elegans.";
RL EMBO J. 24:2566-2578(2005).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLU-90.
RX PubMed=16495308; DOI=10.1242/dev.02300;
RA Dixon S.J., Alexander M., Fernandes R., Ricker N., Roy P.J.;
RT "FGF negatively regulates muscle membrane extension in Caenorhabditis
RT elegans.";
RL Development 133:1263-1275(2006).
RN [8]
RP FUNCTION, INTERACTION WITH SOC-1, AND MUTAGENESIS OF GLY-201.
RX PubMed=16547100; DOI=10.1534/genetics.106.055822;
RA Hopper N.A.;
RT "The adaptor protein soc-1/Gab1 modifies growth factor receptor output in
RT Caenorhabditis elegans.";
RL Genetics 173:163-175(2006).
RN [9]
RP FUNCTION, INTERACTION WITH MIG-2; MIG-13 AND WSP-1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=27780040; DOI=10.1016/j.devcel.2016.09.029;
RA Zhu Z., Chai Y., Jiang Y., Li W., Hu H., Li W., Wu J.W., Wang Z.X.,
RA Huang S., Ou G.;
RT "Functional coordination of WAVE and WASP in C. elegans neuroblast
RT migration.";
RL Dev. Cell 39:224-238(2016).
RN [10]
RP STRUCTURE BY NMR OF 153-214.
RX PubMed=7802869; DOI=10.1038/372375a0;
RA Lim W.A., Richards F.M., Fox R.O.;
RT "Structural determinants of peptide-binding orientation and of sequence
RT specificity in SH3 domains.";
RL Nature 372:375-379(1994).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 155-214.
RX PubMed=9851931; DOI=10.1126/science.282.5396.2088;
RA Nguyen J.T., Turck C.W., Cohen F.E., Zuckermann R.N., Lim W.A.;
RT "Exploiting the basis of proline recognition by SH3 and WW domains: design
RT of N-substituted inhibitors.";
RL Science 282:2088-2092(1998).
CC -!- FUNCTION: Adapter protein which modulates signaling mediated by several
CC receptor tyrosine kinases such as egl-15 and let-23 probably acting
CC upstream of let-60/ras. Negatively regulates vulva induction probably
CC downstream of let-23 (PubMed:1372395, PubMed:16547100). Involved in sex
CC myoblast migration (PubMed:1372395, PubMed:9073451). Negatively
CC regulates fluid homeostasis probably downstream of egl-15
CC (PubMed:1372395, PubMed:11689700). During the formation of
CC neuromuscular junctions at the larval stage, negatively regulates
CC membrane protrusion from body wall muscles probably downstream of egl-
CC 15 (PubMed:16495308). Involved in cytoskeleton dynamics and is
CC recruited by mig-13 to the leading edge of Q neuroblasts and their
CC descendants to signal downstream to activate the wsp-1 pathway and
CC direct migration along the anteroposterior body axis during larval
CC development (PubMed:27780040). Involved in let-23-mediated regulation
CC of fertility independently of let-60/Ras (PubMed:16547100). Negatively
CC regulates daf-2-mediated repression of dauer formation
CC (PubMed:16547100). Plays a role in nicotinic acetylcholine receptor
CC (nAChR)-mediated sensitivity to nicotine (PubMed:15990870). Regulates
CC synaptic levels of nAchR subunit lev-1 in the nerve cord
CC (PubMed:15990870). May play a role in oocyte development upstream of
CC let-60/Ras and the MAP kinase pathway (PubMed:12169634).
CC {ECO:0000269|PubMed:11689700, ECO:0000269|PubMed:12169634,
CC ECO:0000269|PubMed:1372395, ECO:0000269|PubMed:15990870,
CC ECO:0000269|PubMed:16495308, ECO:0000269|PubMed:16547100,
CC ECO:0000269|PubMed:27780040, ECO:0000269|PubMed:9073451}.
CC -!- SUBUNIT: Interacts (probably via SH3 domain 2) with soc-1 (via C-
CC terminus) (PubMed:16547100). Interacts with mig-2 (active GTP-bound
CC form) and wsp-1 (PubMed:27780040). Interacts with mig-13; the
CC interaction is direct (PubMed:27780040). {ECO:0000269|PubMed:16547100,
CC ECO:0000269|PubMed:27780040}.
CC -!- INTERACTION:
CC P29355; Q62245: Sos1; Xeno; NbExp=2; IntAct=EBI-315286, EBI-1693;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27780040}.
CC Note=Targeted to the leading edge of Q neuroblasts by mig-13.
CC {ECO:0000269|PubMed:27780040}.
CC -!- TISSUE SPECIFICITY: Expressed in body wall muscles, pharynx, intestine
CC and hypodermis. {ECO:0000269|PubMed:16495308}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown or RNAi-mediated
CC knockdown in body wall muscles causes ectopic membrane extensions from
CC body wall muscles. {ECO:0000269|PubMed:16495308}.
CC -!- SIMILARITY: Belongs to the GRB2/sem-5/DRK family. {ECO:0000305}.
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DR EMBL; S88446; AAB21850.1; -; mRNA.
DR EMBL; FO080456; CCD63850.1; -; Genomic_DNA.
DR PIR; S25730; S25730.
DR RefSeq; NP_509342.1; NM_076941.5.
DR PDB; 1K76; NMR; -; A=155-214.
DR PDB; 1KFZ; NMR; -; A=155-214.
DR PDB; 1SEM; X-ray; 2.00 A; A/B=155-212.
DR PDB; 2SEM; X-ray; 2.20 A; A/B=155-214.
DR PDB; 3SEM; X-ray; 2.20 A; A/B=155-214.
DR PDBsum; 1K76; -.
DR PDBsum; 1KFZ; -.
DR PDBsum; 1SEM; -.
DR PDBsum; 2SEM; -.
DR PDBsum; 3SEM; -.
DR AlphaFoldDB; P29355; -.
DR SMR; P29355; -.
DR BioGRID; 45979; 139.
DR DIP; DIP-27394N; -.
DR IntAct; P29355; 27.
DR MINT; P29355; -.
DR STRING; 6239.C14F5.5; -.
DR EPD; P29355; -.
DR PaxDb; P29355; -.
DR PeptideAtlas; P29355; -.
DR EnsemblMetazoa; C14F5.5.1; C14F5.5.1; WBGene00004774.
DR GeneID; 181055; -.
DR KEGG; cel:CELE_C14F5.5; -.
DR UCSC; C14F5.5; c. elegans.
DR CTD; 181055; -.
DR WormBase; C14F5.5; CE01784; WBGene00004774; sem-5.
DR eggNOG; KOG3601; Eukaryota.
DR GeneTree; ENSGT00940000155738; -.
DR HOGENOM; CLU_073617_1_0_1; -.
DR InParanoid; P29355; -.
DR OMA; MVPEEML; -.
DR OrthoDB; 1091250at2759; -.
DR PhylomeDB; P29355; -.
DR Reactome; R-CEL-109704; PI3K Cascade.
DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CEL-179812; GRB2 events in EGFR signaling.
DR Reactome; R-CEL-180292; GAB1 signalosome.
DR Reactome; R-CEL-180336; SHC1 events in EGFR signaling.
DR Reactome; R-CEL-182971; EGFR downregulation.
DR Reactome; R-CEL-186763; Downstream signal transduction.
DR Reactome; R-CEL-1963640; GRB2 events in ERBB2 signaling.
DR Reactome; R-CEL-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-CEL-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-CEL-210993; Tie2 Signaling.
DR Reactome; R-CEL-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-CEL-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-CEL-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-CEL-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-CEL-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-CEL-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-CEL-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-CEL-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-CEL-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-CEL-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-CEL-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-CEL-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-CEL-5673001; RAF/MAP kinase cascade.
DR Reactome; R-CEL-6807004; Negative regulation of MET activity.
DR Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-CEL-74751; Insulin receptor signalling cascade.
DR Reactome; R-CEL-8851805; MET activates RAS signaling.
DR Reactome; R-CEL-8851907; MET activates PI3K/AKT signaling.
DR Reactome; R-CEL-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-CEL-8875555; MET activates RAP1 and RAC1.
DR Reactome; R-CEL-8875656; MET receptor recycling.
DR Reactome; R-CEL-9013420; RHOU GTPase cycle.
DR Reactome; R-CEL-912631; Regulation of signaling by CBL.
DR Reactome; R-CEL-9607240; FLT3 Signaling.
DR Reactome; R-CEL-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P29355; -.
DR EvolutionaryTrace; P29355; -.
DR PRO; PR:P29355; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00004774; Expressed in embryo and 4 other tissues.
DR GO; GO:0008180; C:COP9 signalosome; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:WormBase.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IMP:WormBase.
DR GO; GO:0030539; P:male genitalia development; IMP:WormBase.
DR GO; GO:0007517; P:muscle organ development; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0031344; P:regulation of cell projection organization; IMP:WormBase.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0040028; P:regulation of vulval development; IMP:WormBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR043539; Grb2-like.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR46037; PTHR46037; 2.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Membrane; Reference proteome; Repeat;
KW SH2 domain; SH3 domain.
FT CHAIN 1..228
FT /note="Sex muscle abnormal protein 5"
FT /id="PRO_0000088212"
FT DOMAIN 1..58
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 60..152
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 154..213
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT MUTAGEN 49
FT /note="P->L: In n1619; lethal at the larval stage, mild
FT defect in vulva development and partially impaired sex
FT myoblast migration. Rescues fluid accumulation in crl-1
FT e1745ts mutant."
FT /evidence="ECO:0000269|PubMed:1372395"
FT MUTAGEN 87
FT /note="R->Q: In ay73; partial rod-like larval lethality.
FT Surviving mutant have a thin body and no vulva. Rescues
FT fluid accumulation in clr-1 e1745ts mutant."
FT /evidence="ECO:0000269|PubMed:11689700"
FT MUTAGEN 90
FT /note="E->K: In n1779; mild defect in vulva development and
FT partially impaired sex myoblast migration. Causes ectopic
FT muscle membrane extension. Reduced lev-1 synaptic levels.
FT Moderate increase in resistance to nicotine-induced
FT paralysis. Rescues fluid accumulation in crl-1 e1745ts
FT mutant."
FT /evidence="ECO:0000269|PubMed:1372395,
FT ECO:0000269|PubMed:15990870, ECO:0000269|PubMed:16495308"
FT MUTAGEN 91
FT /note="S->N: In n1781; no obvious defects. Partially
FT rescues fluid accumulation in crl-1 e1745ts mutant."
FT /evidence="ECO:0000269|PubMed:1372395"
FT MUTAGEN 201
FT /note="G->R: In n2195; loss of interaction with soc-1.
FT Partially restores normal vulva induction in let-60 n1046gf
FT mutant. Partially rescues fluid accumulation in crl-1
FT e1745ts mutant. Partially prevents constitutive dauer
FT formation in daf-2 m577 mutant."
FT /evidence="ECO:0000269|PubMed:1372395,
FT ECO:0000269|PubMed:16547100"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:1SEM"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:1K76"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:1SEM"
FT STRAND 187..196
FT /evidence="ECO:0007829|PDB:1SEM"
FT STRAND 199..204
FT /evidence="ECO:0007829|PDB:1SEM"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:1SEM"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:1SEM"
SQ SEQUENCE 228 AA; 26210 MW; 2D684C9520646C41 CRC64;
MEAVAEHDFQ AGSPDELSFK RGNTLKVLNK DEDPHWYKAE LDGNEGFIPS NYIRMTECNW
YLGKITRNDA EVLLKKPTVR DGHFLVRQCE SSPGEFSISV RFQDSVQHFK VLRDQNGKYY
LWAVKFNSLN ELVAYHRTAS VSRTHTILLS DMNVETKFVQ ALFDFNPQES GELAFKRGDV
ITLINKDDPN WWEGQLNNRR GIFPSNYVCP YNSNKSNSNV APGFNFGN
