SOS_CAEEL
ID SOS_CAEEL Reviewed; 1493 AA.
AC Q9N5D3; Q9NBD3;
DT 13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Son of sevenless homolog {ECO:0000303|PubMed:10880441};
DE AltName: Full=Guanine nucleotide exchange factor for RAS {ECO:0000305};
GN Name=sos-1 {ECO:0000312|WormBase:T28F12.3a};
GN Synonyms=let-341 {ECO:0000312|WormBase:T28F12.3a};
GN ORFNames=T28F12.3 {ECO:0000312|WormBase:T28F12.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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 [2] {ECO:0000312|EMBL:AAF82360.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1413, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10880441; DOI=10.1093/emboj/19.13.3283;
RA Chang C., Hopper N.A., Sternberg P.W.;
RT "Caenorhabditis elegans SOS-1 is necessary for multiple RAS-mediated
RT developmental signals.";
RL EMBO J. 19:3283-3294(2000).
RN [3] {ECO:0000305}
RP FUNCTION.
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 [4] {ECO:0000305}
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF GLY-322.
RX PubMed=17339331; DOI=10.1128/mcb.01630-06;
RA Modzelewska K., Elgort M.G., Huang J., Jongeward G., Lauritzen A.,
RA Yoon C.H., Sternberg P.W., Moghal N.;
RT "An activating mutation in sos-1 identifies its Dbl domain as a critical
RT inhibitor of the epidermal growth factor receptor pathway during
RT Caenorhabditis elegans vulval development.";
RL Mol. Cell. Biol. 27:3695-3707(2007).
RN [5] {ECO:0000305}
RP INTERACTION WITH CMD-1.
RX PubMed=17854888; DOI=10.1016/j.ceca.2007.07.008;
RA Shen X., Valencia C.A., Gao W., Cotten S.W., Dong B., Huang B.C., Liu R.;
RT "Ca(2+)/Calmodulin-binding proteins from the C. elegans proteome.";
RL Cell Calcium 43:444-456(2008).
RN [6] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF GLU-980.
RX PubMed=25371363; DOI=10.1242/dev.112045;
RA Parry J.M., Sundaram M.V.;
RT "A non-cell-autonomous role for Ras signaling in C. elegans neuroblast
RT delamination.";
RL Development 141:4279-4284(2014).
CC -!- FUNCTION: Promotes the exchange of Ras-bound GDP by GTP (By
CC similarity). May regulate signaling pathways downstream of receptor
CC tyrosine kinase, egl-15 and let-23 (PubMed:10880441). Required for
CC larval and male spicule development, fluid homeostasis, vulva
CC induction, spermatogenesis, and oogenesis by promoting meiosis prophase
CC exit during oocyte maturation (PubMed:10880441, PubMed:17339331).
CC Required for the delamination of G1 cell by promoting the loss of cell
CC junctions and detachment from the excretory system during larval
CC development (PubMed:25371363). Plays a role in nicotinic acetylcholine
CC receptor (nAChR)-mediated sensitivity to nicotine (PubMed:15990870).
CC Regulates synaptic levels of nAchR subunit lev-1 in the nerve cord
CC (PubMed:15990870). {ECO:0000250|UniProtKB:Q62245,
CC ECO:0000269|PubMed:10880441, ECO:0000269|PubMed:15990870,
CC ECO:0000269|PubMed:17339331, ECO:0000269|PubMed:25371363}.
CC -!- SUBUNIT: Interacts with cmd-1 in the presence of Ca(2+).
CC {ECO:0000269|PubMed:17854888}.
CC -!- DOMAIN: The DH (DBL-homology) domain may inhibit the Ras-GEF domain,
CC thereby preventing excessive let-60/Ras activation.
CC {ECO:0000269|PubMed:17339331}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in 8% early
CC larval lethality of the progeny. Surviving animals display slow growth,
CC thin body morphology and both spermatogenesis and oogenesis are
CC arrested at the pachytene stage of meiosis I. In addition, males have
CC short and crumpled spicules. RNAi-mediated knockdown prevents multi-
CC vulva induction in let60 n1046, let-23 sa62 or lin-15 n765 mutants and
CC fluid accumulation in clr-1 e1745ts mutant.
CC {ECO:0000269|PubMed:10880441}.
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DR EMBL; BX284605; CCD72268.1; -; Genomic_DNA.
DR EMBL; AF251308; AAF82360.1; -; mRNA.
DR RefSeq; NP_504235.2; NM_071834.4.
DR AlphaFoldDB; Q9N5D3; -.
DR SMR; Q9N5D3; -.
DR IntAct; Q9N5D3; 2.
DR MINT; Q9N5D3; -.
DR STRING; 6239.T28F12.3; -.
DR EPD; Q9N5D3; -.
DR PaxDb; Q9N5D3; -.
DR PeptideAtlas; Q9N5D3; -.
DR PRIDE; Q9N5D3; -.
DR EnsemblMetazoa; T28F12.3a.1; T28F12.3a.1; WBGene00004947.
DR GeneID; 178846; -.
DR KEGG; cel:CELE_T28F12.3; -.
DR UCSC; T28F12.3; c. elegans.
DR CTD; 178846; -.
DR WormBase; T28F12.3a; CE36328; WBGene00004947; sos-1.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000169087; -.
DR HOGENOM; CLU_002744_0_0_1; -.
DR InParanoid; Q9N5D3; -.
DR OMA; WVARSIV; -.
DR OrthoDB; 576110at2759; -.
DR PhylomeDB; Q9N5D3; -.
DR Reactome; R-CEL-179812; GRB2 events in EGFR signaling.
DR Reactome; R-CEL-180336; SHC1 events in EGFR signaling.
DR Reactome; R-CEL-186763; Downstream signal transduction.
DR Reactome; R-CEL-193648; NRAGE signals death through JNK.
DR Reactome; R-CEL-1963640; GRB2 events in ERBB2 signaling.
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-416482; G alpha (12/13) signalling events.
DR Reactome; R-CEL-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-CEL-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-CEL-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-CEL-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-CEL-5673001; RAF/MAP kinase cascade.
DR Reactome; R-CEL-74751; Insulin receptor signalling cascade.
DR Reactome; R-CEL-8851805; MET activates RAS signaling.
DR Reactome; R-CEL-9013149; RAC1 GTPase cycle.
DR Reactome; R-CEL-9607240; FLT3 Signaling.
DR SignaLink; Q9N5D3; -.
DR PRO; PR:Q9N5D3; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00004947; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; Q9N5D3; baseline and differential.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IPI:WormBase.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:WormBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0016477; P:cell migration; IMP:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0007292; P:female gamete generation; IMP:WormBase.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0040026; P:positive regulation of vulval development; IGI:WormBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.20.10; -; 1.
DR Gene3D; 1.10.840.10; -; 2.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW Guanine-nucleotide releasing factor; Reference proteome.
FT CHAIN 1..1493
FT /note="Son of sevenless homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000435955"
FT DOMAIN 244..448
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 496..606
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 656..824
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 897..1164
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 1067..1091
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1165..1248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1263..1493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1204..1248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1276..1291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1304..1326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1341..1365
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1382..1405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1425..1451
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1452..1468
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 322
FT /note="G->R: In sy262; restores normal vulva induction in
FT let-23 sy-1 mutant."
FT /evidence="ECO:0000269|PubMed:17339331"
FT MUTAGEN 980
FT /note="E->K: In cs41; temperature sensitive mutant in which
FT G1 cell fails to delaminate during the excretory system
FT development."
FT /evidence="ECO:0000269|PubMed:25371363"
SQ SEQUENCE 1493 AA; 169916 MW; 2E61A851ACA2ECF9 CRC64;
MSIMSISLHS ASSDTVSLTS RRTISTSKHW AAIFDERIYQ ICNIVHPGLP IDNAAVEHIR
YFLQSIVFEL IEARATSVVE VDKTAKKLFA FGLQTVCKEA WDNMHQQLQK HKYQKALKTV
LESQHRLAAV IKETLGPREK EKKDREKKEI ERIACYIYYA CESVTEDVLR LTGNYVKNIR
NSEQKITMAN LDVAMNGDKA LMELRTKLRN EEEAESPGGF GFLSEFEEFV AEETEEKTLS
NSQTYESVAV DFLRDERRFI RELNRINVFR RRIESVAATD VDKQIVCNLF GNLTEIHDLA
LKIERTLEDA IELSDTQCIG MGIWEHGEAY EFDTYTFYIR RDGGEMNETR HATYVINDNI
KALLESERFA SLFQSGEHYL GSSLDGQSFR LAVQYVLPQL LHIPIFHIYQ YHEYITRLHQ
LSSSEEDRRD LNDCRSAFER VVGCVSDMSP ELKTKITQFL DQQAKSEKIY NVKRLNEIQS
SIDGFTGSPI GKTCNELEKD GDLGMIRPSL QFSSEITKNK KWKTERFVYI FDQMIVLCKR
HRNTLKFKDR LAVHSIDVFD IPDSEVTNCF KIESHDKSSL PKIYHFVCKN PEEKRQWMAV
LVKVTTKSVL DRILDNHEKE EAKRIPLVVP GPDQYRFSEP DTEDNISFED YTSSSGIPVI
KCGTVLKLIE RLTYHSYTDS KYILTFLISY RSFCTPNDLF SLLLERFNIP TPKKLQQPKQ
GGGPLAGRYD TVQSHGLSAI SSSSCINPLC EQKFRKEFQQ PIQLRVLSVI NQWVKLHWYD
FQCDPVLLDA LELFLNRCCD PREGLSKQHK KFCKTILALI EKRVKNPPGI MQQPNENGDK
GAADEGHVNS AFVFGDDQQH PPQHQVYTNE SPKETNQVLW HTAQKGDVDH YDLLTLHPIE
IGRQLTLLHS DLYRAIQPIE LVEAAWTKAE KWRKSPQLLR LTDHSTLLTY WVSRSIVETE
SLEERMAMFN RVLEVMSVFE ELHNFTGLVA FYSALNSSCI FRLKWCWDGL DNEKKKCFDR
FNTLCERRWQ EMQKRLSSIN PPCIPFFGHY LSNIYFLEQG NSTFVNKSPP HGAAGAQKQQ
KDDLKASDPE NSNKQFKQLV SFLKLRKISN VIREIQIFQD QRYSLTLEPT IRQFFESINP
KNDFKSNEDL EEYLYNKSLE IQPKGLDTPT AELKPKHNAS TLRSPGVKPP KAAGNHYSAN
HPIGLHLHSQ NSHSAPHAMS SQSSTVPNTP LSAHETKRSL SHNQDDAPLQ QFVDIRFERK
GTHPKIPVLQ PPPLLPRSSR ANQSNSVSLP PTTQAPMPPA PKSSGMMSTA TSPTTLTTTT
TPSSAGGPPP KLHPRRMTQQ PMSPLAKSPL TPSRDNSSPS AFQFPVVYEA STAPPLPPRP
STSSDVSSSP STSGSTSSAT KENQEQLRVI FDREESHSPT VRLSVPLPPA LPPPRGSSVF
RAPPPLPPKS NRHNSNSPTL SSEQPFEDPM SPSIFVNTPP PPLPPKTYRS SNK
