LET60_CAEEL
ID LET60_CAEEL Reviewed; 184 AA.
AC P22981;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ras protein let-60;
DE AltName: Full=Abnormal cell lineage protein 34;
DE AltName: Full=Lethal protein 60;
DE Flags: Precursor;
GN Name=let-60 {ECO:0000312|WormBase:ZK792.6};
GN Synonyms=lin-34 {ECO:0000312|WormBase:ZK792.6};
GN ORFNames=ZK792.6 {ECO:0000312|WormBase:ZK792.6};
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], AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=2257629; DOI=10.1016/0092-8674(90)90495-z;
RA Han M., Sternberg P.W.;
RT "let-60, a gene that specifies cell fates during C. elegans vulval
RT induction, encodes a ras protein.";
RL Cell 63:921-931(1990).
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, AND MUTAGENESIS OF GLY-13.
RX PubMed=2123303; DOI=10.1038/348503a0;
RA Beitel G.J., Clark S.C., Horvitz H.R.;
RT "Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of
RT vulval induction.";
RL Nature 348:503-509(1990).
RN [4]
RP INTERACTION WITH SOC-2.
RX PubMed=9674433; DOI=10.1016/s0092-8674(00)81227-1;
RA Sieburth D.S., Sun Q., Han M.;
RT "SUR-8, a conserved Ras-binding protein with leucine-rich repeats,
RT positively regulates Ras-mediated signaling in C. elegans.";
RL Cell 94:119-130(1998).
RN [5]
RP INTERACTION WITH PLC-1.
RX PubMed=9497345; DOI=10.1074/jbc.273.11.6218;
RA Shibatohge M., Kariya K., Liao Y., Hu C.-D., Watari Y., Goshima M.,
RA Shima F., Kataoka T.;
RT "Identification of PLC210, a Caenorhabditis elegans phospholipase C, as a
RT putative effector of Ras.";
RL J. Biol. Chem. 273:6218-6222(1998).
RN [6]
RP POSSIBLE FUNCTION IN GEF ACTIVITY.
RX PubMed=10608844; DOI=10.1074/jbc.274.53.37815;
RA Liao Y., Kariya K., Hu C.-D., Shibatohge M., Goshima M., Okada T.,
RA Watari Y., Gao X., Jin T.-G., Yamawaki-Kataoka Y., Kataoka T.;
RT "RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a
RT Ras/Rap1A-associating domain, is conserved between nematode and humans.";
RL J. Biol. Chem. 274:37815-37820(1999).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF GLY-13.
RX PubMed=20230814; DOI=10.1016/j.ydbio.2010.03.004;
RA Simms C.L., Baillie D.L.;
RT "A strawberry notch homolog, let-765/nsh-1, positively regulates lin-3/egf
RT expression to promote RAS-dependent vulval induction in C. elegans.";
RL Dev. Biol. 341:472-485(2010).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF GLY-13.
RX PubMed=23103556; DOI=10.1016/j.yexcr.2012.10.008;
RA Iwasa H., Kuroyanagi H., Maimaiti S., Ikeda M., Nakagawa K., Hata Y.;
RT "Characterization of RSF-1, the Caenorhabditis elegans homolog of the Ras-
RT association domain family protein 1.";
RL Exp. Cell Res. 319:1-11(2013).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLY-13.
RX PubMed=24929033; DOI=10.1016/j.gep.2014.05.005;
RA Weinberg F., Schulze E., Fatouros C., Schmidt E., Baumeister R.,
RA Brummer T.;
RT "Expression pattern and first functional characterization of riok-1 in
RT Caenorhabditis elegans.";
RL Gene Expr. Patterns 15:124-134(2014).
RN [10]
RP FUNCTION.
RX PubMed=28135265; DOI=10.1371/journal.pgen.1006592;
RA Walser M., Umbricht C.A., Froehli E., Nanni P., Hajnal A.;
RT "beta-Integrin de-phosphorylation by the density-enhanced phosphatase DEP-1
RT attenuates EGFR signaling in C. elegans.";
RL PLoS Genet. 13:E1006592-E1006592(2017).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF GLY-13.
RX PubMed=32053105; DOI=10.7554/elife.50986;
RA Haag A., Walser M., Henggeler A., Hajnal A.;
RT "The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling
RT in C. elegans and in human cells.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: The level of let-60 controls the switch between vulval and
CC hypodermal cell fates during C.elegans vulval induction
CC (PubMed:2257629, PubMed:2123303, PubMed:24929033, PubMed:28135265,
CC PubMed:20230814, PubMed:32053105, PubMed:23103556). May stimulate the
CC guanine nucleotide exchange factor (GEF) activity of rap-1
CC (PubMed:10608844). May induce nuclear condensation (PubMed:23103556).
CC {ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:20230814,
CC ECO:0000269|PubMed:2123303, ECO:0000269|PubMed:2257629,
CC ECO:0000269|PubMed:23103556, ECO:0000269|PubMed:24929033,
CC ECO:0000269|PubMed:28135265, ECO:0000269|PubMed:32053105}.
CC -!- SUBUNIT: Interacts with soc-2 (PubMed:9674433). Interacts (in GTP-bound
CC form) with plc-1 (via Ras-associating domain 1) (PubMed:9497345).
CC {ECO:0000269|PubMed:9497345, ECO:0000269|PubMed:9674433}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor.
CC -!- TISSUE SPECIFICITY: Expressed in body wall muscles and in the nervous
CC system including ganglion, nerve ring dorsal and ventral nerve cords,
CC motor neurons and sensory tail neurons. {ECO:0000269|PubMed:24929033}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28103.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M55535; AAA28103.1; ALT_INIT; mRNA.
DR EMBL; BX284604; CAA92630.1; -; Genomic_DNA.
DR PIR; A36290; A36290.
DR RefSeq; NP_502213.3; NM_069812.3.
DR AlphaFoldDB; P22981; -.
DR SMR; P22981; -.
DR BioGRID; 43199; 140.
DR DIP; DIP-25369N; -.
DR IntAct; P22981; 6.
DR MINT; P22981; -.
DR STRING; 6239.ZK792.6; -.
DR EPD; P22981; -.
DR PaxDb; P22981; -.
DR PeptideAtlas; P22981; -.
DR EnsemblMetazoa; ZK792.6.1; ZK792.6.1; WBGene00002335.
DR GeneID; 178104; -.
DR KEGG; cel:CELE_ZK792.6; -.
DR UCSC; ZK792.6; c. elegans.
DR CTD; 178104; -.
DR WormBase; ZK792.6; CE03827; WBGene00002335; let-60.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000155653; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P22981; -.
DR OMA; SSRRFKC; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P22981; -.
DR Reactome; R-CEL-1169092; Activation of RAS in B cells.
DR Reactome; R-CEL-171007; p38MAPK events.
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-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-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-CEL-4086398; Ca2+ pathway.
DR Reactome; R-CEL-5621575; CD209 (DC-SIGN) signaling.
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-5673000; RAF activation.
DR Reactome; R-CEL-5673001; RAF/MAP kinase cascade.
DR Reactome; R-CEL-5674135; MAP2K and MAPK activation.
DR Reactome; R-CEL-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR Reactome; R-CEL-8851805; MET activates RAS signaling.
DR Reactome; R-CEL-8951936; RUNX3 regulates p14-ARF.
DR Reactome; R-CEL-9607240; FLT3 Signaling.
DR Reactome; R-CEL-9634635; Estrogen-stimulated signaling through PRKCZ.
DR Reactome; R-CEL-9648002; RAS processing.
DR SignaLink; P22981; -.
DR PRO; PR:P22981; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002335; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IDA:WormBase.
DR GO; GO:0003924; F:GTPase activity; ISS:WormBase.
DR GO; GO:0043274; F:phospholipase binding; IPI:WormBase.
DR GO; GO:0120283; F:protein serine/threonine kinase binding; IPI:WormBase.
DR GO; GO:0008306; P:associative learning; IGI:WormBase.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IGI:WormBase.
DR GO; GO:0007517; P:muscle organ development; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IGI:WormBase.
DR GO; GO:1902685; P:positive regulation of receptor localization to synapse; IMP:WormBase.
DR GO; GO:0040026; P:positive regulation of vulval development; IMP:WormBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0042659; P:regulation of cell fate specification; IMP:WormBase.
DR GO; GO:0031344; P:regulation of cell projection organization; IMP:WormBase.
DR GO; GO:0040028; P:regulation of vulval development; IGI:UniProtKB.
DR GO; GO:0000003; P:reproduction; IGI:WormBase.
DR GO; GO:0007614; P:short-term memory; IGI:WormBase.
DR GO; GO:0072327; P:vulval cell fate specification; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Reference proteome.
FT CHAIN 1..181
FT /note="Ras protein let-60"
FT /id="PRO_0000082686"
FT PROPEP 182..184
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281335"
FT MOTIF 32..40
FT /note="Effector region"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 57..61
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 181
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 181
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 13
FT /note="G->E: In n1046; multivulva phenotype. The
FT multivulval phenotype is enhanced in a chp-1 tm2277 mutant
FT background. The multivula phenotype is suppressed in a rsf-
FT 1 tm5002 mutant background. RNAi-mediated knockdown of let-
FT 765 suppresses the multivulva phenotype."
FT /evidence="ECO:0000269|PubMed:20230814,
FT ECO:0000269|PubMed:2123303, ECO:0000269|PubMed:23103556,
FT ECO:0000269|PubMed:24929033"
SQ SEQUENCE 184 AA; 20983 MW; D32BA6B67DAE14F9 CRC64;
MTEYKLVVVG DGGVGKSALT IQLIQNHFVE EYDPTIEDSY RKQVVIDGET CLLDILDTAG
QEEYSAMRDQ YMRTGEGFLL VFAVNEAKSF ENVANYREQI RRVKDSDDVP MVLVGNKCDL
SSRSVDFRTV SETAKGYGIP NVDTSAKTRM GVDEAFYTLV REIRKHRERH DNNKPQKKKK
CQIM
