ID INSR_CAEEL Reviewed; 1846 AA.
AC Q968Y9; A0A0K3AUY1; B5QS63; O16131;
DT 03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 27-MAR-2024, entry version 179.
DE RecName: Full=Insulin-like receptor {ECO:0000250|UniProtKB:P06213};
DE Short=IR {ECO:0000250|UniProtKB:P06213};
DE EC=2.7.10.1;
DE AltName: Full=Abnormal dauer formation protein 2 {ECO:0000303|PubMed:9252323};
DE Contains:
DE RecName: Full=Insulin-like receptor subunit alpha {ECO:0000250|UniProtKB:P06213};
DE Contains:
DE RecName: Full=Insulin-like receptor subunit beta {ECO:0000250|UniProtKB:P06213};
DE Flags: Precursor;
GN Name=daf-2 {ECO:0000312|WormBase:Y55D5A.5a};
GN ORFNames=Y55D5A.5 {ECO:0000312|WormBase:Y55D5A.5a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC47715.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF CYS-401; CYS-469; PRO-470; SER-573; ASP-648; ASP-1374; PRO-1434 AND
RP PRO-1465.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC47715.1};
RX PubMed=9252323; DOI=10.1126/science.277.5328.942;
RA Kimura K.D., Tissenbaum H.A., Liu Y., Ruvkun G.;
RT "daf-2, an insulin receptor-like gene that regulates longevity and diapause
RT in Caenorhabditis elegans.";
RL Science 277:942-946(1997).
RN [2] {ECO:0000305}
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] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-1465.
RX PubMed=9790527; DOI=10.1016/s0092-8674(00)81751-1;
RA Apfeld J., Kenyon C.;
RT "Cell nonautonomy of C. elegans daf-2 function in the regulation of
RT diapause and life span.";
RL Cell 95:199-210(1998).
RN [4] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ALA-580 AND PRO-1465.
RX PubMed=11274053; DOI=10.1101/gad.867301;
RA Pierce S.B., Costa M., Wisotzkey R., Devadhar S., Homburger S.A.,
RA Buchman A.R., Ferguson K.C., Heller J., Platt D.M., Pasquinelli A.A.,
RA Liu L.X., Doberstein S.K., Ruvkun G.;
RT "Regulation of DAF-2 receptor signaling by human insulin and ins-1, a
RT member of the unusually large and diverse C. elegans insulin gene family.";
RL Genes Dev. 15:672-686(2001).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLY-383.
RX PubMed=11743719; DOI=10.1006/jmbi.2000.5210;
RA Yu H., Larsen P.L.;
RT "DAF-16-dependent and independent expression targets of DAF-2 insulin
RT receptor-like pathway in Caenorhabditis elegans include FKBPs.";
RL J. Mol. Biol. 314:1017-1028(2001).
RN [6]
RP MUTAGENESIS OF GLY-383; ASP-1374 AND PRO-1465.
RX PubMed=16950159; DOI=10.1016/j.neuron.2006.07.024;
RA Tomioka M., Adachi T., Suzuki H., Kunitomo H., Schafer W.R., Iino Y.;
RT "The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in
RT Caenorhabditis elegans.";
RL Neuron 51:613-625(2006).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-364; ASN-453; ASN-696; ASN-1017
RP AND ASN-1078, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-1465.
RX PubMed=18782349; DOI=10.1111/j.1474-9726.2008.00435.x;
RA Evans E.A., Chen W.C., Tan M.-W.;
RT "The DAF-2 insulin-like signaling pathway independently regulates aging and
RT immunity in C. elegans.";
RL Aging Cell 7:879-893(2008).
RN [9]
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-383; GLY-547; CYS-1045;
RP PRO-1434 AND PRO-1465.
RX PubMed=18436204; DOI=10.1016/j.ydbio.2008.03.019;
RA Dixon S.J., Alexander M., Chan K.K., Roy P.J.;
RT "Insulin-like signaling negatively regulates muscle arm extension through
RT DAF-12 in Caenorhabditis elegans.";
RL Dev. Biol. 318:153-161(2008).
RN [10]
RP ACTIVITY REGULATION, AND INTERACTION WITH SHC-1.
RX PubMed=18832074; DOI=10.1101/gad.478408;
RA Neumann-Haefelin E., Qi W., Finkbeiner E., Walz G., Baumeister R.,
RA Hertweck M.;
RT "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to
RT modulate life span and stress response in C. elegans.";
RL Genes Dev. 22:2721-2735(2008).
RN [11]
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-146 AND PRO-1465.
RX PubMed=18245374; DOI=10.1534/genetics.107.070813;
RA Patel D.S., Garza-Garcia A., Nanji M., McElwee J.J., Ackerman D.,
RA Driscoll P.C., Gems D.;
RT "Clustering of genetically defined allele classes in the Caenorhabditis
RT elegans DAF-2 insulin/IGF-1 receptor.";
RL Genetics 178:931-946(2008).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF PRO-1465.
RX PubMed=21334311; DOI=10.1016/j.bbrc.2011.02.079;
RA Fierro-Gonzalez J.C., Gonzalez-Barrios M., Miranda-Vizuete A., Swoboda P.;
RT "The thioredoxin TRX-1 regulates adult lifespan extension induced by
RT dietary restriction in Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 406:478-482(2011).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF PRO-1465.
RX PubMed=21471153; DOI=10.1242/dev.057109;
RA Huang X., Zhang H., Zhang H.;
RT "The zinc-finger protein SEA-2 regulates larval developmental timing and
RT adult lifespan in C. elegans.";
RL Development 138:2059-2068(2011).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22560223; DOI=10.1016/j.cmet.2012.04.007;
RA Robida-Stubbs S., Glover-Cutter K., Lamming D.W., Mizunuma M.,
RA Narasimhan S.D., Neumann-Haefelin E., Sabatini D.M., Blackwell T.K.;
RT "TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf
RT and DAF-16/FoxO.";
RL Cell Metab. 15:713-724(2012).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF PRO-1465.
RX PubMed=22278922; DOI=10.1242/dev.074047;
RA Korta D.Z., Tuck S., Hubbard E.J.;
RT "S6K links cell fate, cell cycle and nutrient response in C. elegans
RT germline stem/progenitor cells.";
RL Development 139:859-870(2012).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF PRO-1465.
RX PubMed=22916022; DOI=10.1371/journal.pgen.1002836;
RA Qi W., Huang X., Neumann-Haefelin E., Schulze E., Baumeister R.;
RT "Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of
RT Caenorhabditis elegans.";
RL PLoS Genet. 8:e1002836-e1002836(2012).
RN [17]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-1434 AND PRO-1465.
RX PubMed=24332851; DOI=10.1016/j.celrep.2013.11.018;
RA Chen D., Li P.W., Goldstein B.A., Cai W., Thomas E.L., Chen F.,
RA Hubbard A.E., Melov S., Kapahi P.;
RT "Germline signaling mediates the synergistically prolonged longevity
RT produced by double mutations in daf-2 and rsks-1 in C. elegans.";
RL Cell Rep. 5:1600-1610(2013).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-573.
RX PubMed=24385923; DOI=10.1371/journal.pgen.1004020;
RA Ferguson A.A., Roy S., Kormanik K.N., Kim Y., Dumas K.J., Ritov V.B.,
RA Matern D., Hu P.J., Fisher A.L.;
RT "TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal
RT that influences developmental decisions and longevity in Caenorhabditis
RT elegans.";
RL PLoS Genet. 9:e1004020-e1004020(2013).
RN [19]
RP FUNCTION, INTERACTION WITH DAF-18, AND MUTAGENESIS OF PRO-1465.
RX PubMed=23995781; DOI=10.1038/onc.2013.347;
RA Liu J., Visser-Grieve S., Boudreau J., Yeung B., Lo S., Chamberlain G.,
RA Yu F., Sun T., Papanicolaou T., Lam A., Yang X., Chin-Sang I.;
RT "Insulin activates the insulin receptor to downregulate the PTEN tumour
RT suppressor.";
RL Oncogene 33:3878-3885(2014).
RN [20]
RP FUNCTION (ISOFORMS A AND C), SUBCELLULAR LOCATION (ISOFORM C), AND
RP INTERACTION WITH CASY-1 (ISOFORM C).
RX PubMed=25035490; DOI=10.1126/science.1250709;
RA Ohno H., Kato S., Naito Y., Kunitomo H., Tomioka M., Iino Y.;
RT "Role of synaptic phosphatidylinositol 3-kinase in a behavioral learning
RT response in C. elegans.";
RL Science 345:313-317(2014).
RN [21]
RP MUTAGENESIS OF PRO-1465.
RX PubMed=26552888; DOI=10.1242/dev.130252;
RA Narbonne P., Maddox P.S., Labbe J.C.;
RT "DAF-18/PTEN locally antagonizes insulin signalling to couple germline stem
RT cell proliferation to oocyte needs in C. elegans.";
RL Development 142:4230-4241(2015).
RN [22]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-1465.
RX PubMed=28853436; DOI=10.1038/ncomms16083;
RA Tiku V., Jain C., Raz Y., Nakamura S., Heestand B., Liu W., Spaeth M.,
RA Suchiman H.E.D., Mueller R.U., Slagboom P.E., Partridge L., Antebi A.;
RT "Small nucleoli are a cellular hallmark of longevity.";
RL Nat. Commun. 8:16083-16083(2016).
RN [23]
RP FUNCTION, AND MUTAGENESIS OF PRO-1465.
RX PubMed=29500338; DOI=10.1038/s41467-018-02934-5;
RA De Magalhaes Filho C.D., Henriquez B., Seah N.E., Evans R.M.,
RA Lapierre L.R., Dillin A.;
RT "Visible light reduces C. elegans longevity.";
RL Nat. Commun. 9:927-927(2018).
CC -!- FUNCTION: Insulin receptor-like tyrosine kinase which regulates
CC metabolism, controls longevity and prevents developmental arrest at the
CC dauer stage (PubMed:9252323, PubMed:9790527, PubMed:11743719,
CC PubMed:24332851, PubMed:28853436, PubMed:21334311, PubMed:29500338,
CC PubMed:24385923, PubMed:22916022). Binding of INS family members may
CC either stimulate, or antagonize, association of the receptor with
CC downstream mediators such as pdk-1 and age-1 (PubMed:11274053).
CC Required for germline progenitor proliferation during larval
CC development (PubMed:22278922). Plays a role in maintaining gonad
CC integrity in a daf-16/FOXO-dependent manner (PubMed:22916022). Required
CC for the response to environmental stimuli such as light, food,
CC pheromone, and temperature (PubMed:24332851, PubMed:29500338).
CC Negatively regulates resistance to UV and oxidative stress
CC (PubMed:24332851). In a daf-16/FOXO-dependent manner, plays a role in
CC regulating the response to white light (PubMed:29500338). Role in
CC immune function and pathogen resistance (PubMed:18782349). Negatively
CC regulates autophagy (PubMed:22560223). Regulates daf-18/PTEN protein
CC levels (PubMed:23995781). Plays a role in controlling seam cell
CC development during the larval stages (PubMed:21471153).
CC {ECO:0000269|PubMed:11274053, ECO:0000269|PubMed:11743719,
CC ECO:0000269|PubMed:18782349, ECO:0000269|PubMed:21334311,
CC ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:22278922,
CC ECO:0000269|PubMed:22560223, ECO:0000269|PubMed:22916022,
CC ECO:0000269|PubMed:23995781, ECO:0000269|PubMed:24332851,
CC ECO:0000269|PubMed:24385923, ECO:0000269|PubMed:29500338,
CC ECO:0000269|PubMed:9252323, ECO:0000269|PubMed:9790527}.
CC -!- FUNCTION: [Isoform a]: Required for taste avoidance learning in the
CC cell body of ASER gustatory neurons. {ECO:0000269|PubMed:25035490}.
CC -!- FUNCTION: [Isoform c]: Required for taste avoidance learning in axons
CC of ASER gustatory neurons. {ECO:0000269|PubMed:25035490}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000250|UniProtKB:P06213, ECO:0000255|PROSITE-
CC ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Autophosphorylation activates the kinase activity
CC (By similarity). Interaction with shc-1 may inhibit its activity
CC (PubMed:18832074). {ECO:0000250|UniProtKB:P06213,
CC ECO:0000269|PubMed:18832074}.
CC -!- SUBUNIT: Tetramer of 2 alpha and 2 beta chains linked by disulfide
CC bonds. The alpha chains contribute to the formation of the ligand-
CC binding domain, while the beta chains carry the kinase domain (By
CC similarity). Interacts (via cytoplasmic domain) with shc-1 (PID domain)
CC (PubMed:18832074). Interacts (via kinase domain) with daf-18 (via C-
CC terminus) (PubMed:23995781). {ECO:0000250|UniProtKB:P06213,
CC ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:23995781}.
CC -!- SUBUNIT: [Isoform c]: Interacts with casy-1; promoting axonal
CC localization. {ECO:0000269|PubMed:25035490}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P06213}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:P06213}.
CC -!- SUBCELLULAR LOCATION: [Isoform c]: Cell projection, axon
CC {ECO:0000269|PubMed:25035490}. Note=Localizes to the synapse-rich
CC neurite that extends axons. Casy-1 is required for axonal localization.
CC {ECO:0000269|PubMed:25035490}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q968Y9-1; Sequence=Displayed;
CC Name=c;
CC IsoId=Q968Y9-3; Sequence=VSP_061883;
CC -!- DISRUPTION PHENOTYPE: Accumulation of fat, pigmented intestine,
CC increased lifespan, increased dauer formation and increased resistance
CC to pathogens. Severe loss of function mutants display recessive early
CC embryonic lethality (PubMed:9252323, PubMed:9790527, PubMed:11274053,
CC PubMed:18782349, PubMed:18245374). RNAi-mediated knockdown in germline,
CC hypodermis, intestine or in muscles causes increased lifespan
CC (PubMed:24332851, PubMed:28853436). RNAi-mediated knockdown in a ncl-1
CC mutant (e1942) background reduces the increased longevity of the daf-2
CC single mutant, and reduces the increased ribosomal protein synthesis in
CC the ncl-1 single mutant (e1942) (PubMed:28853436). RNAi-mediated
CC knockdown in adults causes an increase in lgg-1 positive autophagic
CC vesicles (PubMed:22560223). RNAi-mediated knockdown results in an
CC increase in the number of muscle arm extensions (PubMed:18436204).
CC RNAi-mediated knockdown together with tatn-1 RNAi extends the lifespan
CC of the single daf-2 RNAi mutant (PubMed:24385923).
CC {ECO:0000269|PubMed:11274053, ECO:0000269|PubMed:18245374,
CC ECO:0000269|PubMed:18436204, ECO:0000269|PubMed:18782349,
CC ECO:0000269|PubMed:22560223, ECO:0000269|PubMed:24332851,
CC ECO:0000269|PubMed:24385923, ECO:0000269|PubMed:28853436,
CC ECO:0000269|PubMed:9252323, ECO:0000269|PubMed:9790527}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AF012437; AAC47715.1; -; mRNA.
DR EMBL; BX284603; CCD72201.2; -; Genomic_DNA.
DR EMBL; BX284603; CTQ86616.1; -; Genomic_DNA.
DR PIR; T42047; T42047.
DR RefSeq; NP_001299916.1; NM_001312987.1. [Q968Y9-3]
DR RefSeq; NP_497650.4; NM_065249.4. [Q968Y9-1]
DR AlphaFoldDB; Q968Y9; -.
DR SMR; Q968Y9; -.
DR BioGRID; 40655; 168.
DR STRING; 6239.Y55D5A.5c.2; -.
DR TCDB; 8.A.23.1.30; the basigin (basigin) family.
DR GlyCosmos; Q968Y9; 13 sites, No reported glycans.
DR iPTMnet; Q968Y9; -.
DR EPD; Q968Y9; -.
DR PaxDb; 6239-Y55D5A-5a; -.
DR PeptideAtlas; Q968Y9; -.
DR EnsemblMetazoa; Y55D5A.5a.1; Y55D5A.5a.1; WBGene00000898. [Q968Y9-1]
DR EnsemblMetazoa; Y55D5A.5c.1; Y55D5A.5c.1; WBGene00000898. [Q968Y9-3]
DR GeneID; 175410; -.
DR KEGG; cel:CELE_Y55D5A.5; -.
DR AGR; WB:WBGene00000898; -.
DR WormBase; Y55D5A.5a; CE46852; WBGene00000898; daf-2.
DR WormBase; Y55D5A.5c; CE50204; WBGene00000898; daf-2.
DR eggNOG; KOG4258; Eukaryota.
DR GeneTree; ENSGT00940000170078; -.
DR HOGENOM; CLU_000288_166_3_1; -.
DR InParanoid; Q968Y9; -.
DR OMA; HRCWHHR; -.
DR OrthoDB; 223327at2759; -.
DR PhylomeDB; Q968Y9; -.
DR Reactome; R-CEL-77387; Insulin receptor recycling.
DR SignaLink; Q968Y9; -.
DR PRO; PR:Q968Y9; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000898; Expressed in embryo and 4 other cell types or tissues.
DR ExpressionAtlas; Q968Y9; baseline and differential.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:WormBase.
DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0097730; C:non-motile cilium; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; ISS:WormBase.
DR GO; GO:0005009; F:insulin receptor activity; ISS:WormBase.
DR GO; GO:0043560; F:insulin receptor substrate binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017046; F:peptide hormone binding; ISS:WormBase.
DR GO; GO:0019901; F:protein kinase binding; IPI:WormBase.
DR GO; GO:0051425; F:PTB domain binding; IPI:WormBase.
DR GO; GO:0042169; F:SH2 domain binding; IPI:WormBase.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:1902075; P:cellular response to salt; IMP:UniProtKB.
DR GO; GO:0043054; P:dauer exit; IMP:WormBase.
DR GO; GO:0040024; P:dauer larval development; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IGI:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central.
DR GO; GO:0010286; P:heat acclimation; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:WormBase.
DR GO; GO:0030536; P:larval feeding behavior; IMP:UniProtKB.
DR GO; GO:1905910; P:negative regulation of dauer entry; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0010888; P:negative regulation of lipid storage; IMP:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:WormBase.
DR GO; GO:1900075; P:positive regulation of neuromuscular synaptic transmission; IGI:UniProtKB.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IMP:WormBase.
DR GO; GO:2000785; P:regulation of autophagosome assembly; IMP:BHF-UCL.
DR GO; GO:1905909; P:regulation of dauer entry; IGI:UniProtKB.
DR GO; GO:0061065; P:regulation of dauer larval development; IMP:UniProtKB.
DR GO; GO:0040034; P:regulation of development, heterochronic; IGI:WormBase.
DR GO; GO:1903998; P:regulation of eating behavior; IMP:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IGI:UniProtKB.
DR GO; GO:0010883; P:regulation of lipid storage; IGI:UniProtKB.
DR GO; GO:1901031; P:regulation of response to reactive oxygen species; IMP:WormBase.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0009411; P:response to UV; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 2.
DR CDD; cd05032; PTKc_InsR_like; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR Gene3D; 3.80.20.20; Receptor L-domain; 2.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR PANTHER; PTHR24416:SF525; INSULIN-LIKE RECEPTOR; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; Fibronectin type III; 2.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF52058; L domain-like; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calcium; Carbohydrate metabolism;
KW Cell adhesion; Cell projection; Cleavage on pair of basic residues;
KW Developmental protein; Disulfide bond; Glycoprotein; Immunity;
KW Innate immunity; Kinase; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT CHAIN ?..966
FT /note="Insulin-like receptor subunit alpha"
FT /evidence="ECO:0000255"
FT /id="PRO_0000386619"
FT CHAIN 970..1846
FT /note="Insulin-like receptor subunit beta"
FT /evidence="ECO:0000255"
FT /id="PRO_0000386620"
FT TOPO_DOM 970..1183
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1184..1204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1205..1846
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 775..869
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 969..1067
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1077..1179
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1246..1528
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 944..980
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1718..1742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1769..1826
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1723..1742
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1769..1797
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1806..1826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1388
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10028"
FT BINDING 1252..1260
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 652
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 671
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 696
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 1017
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 1047
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1078
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 1087
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1093
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 371..386
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 393..401
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 397..410
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 413..422
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 426..438
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 469..483
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 486..490
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 615..646
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 706
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT VAR_SEQ 924
FT /note="R -> RCDIKNDPVGCAMLLLPPEIDDSDVGDDDEEPGGGSEQQQRILRNSE
FT ILKRQKRQILGRSLGGIHGIRSIGRKEYEQFADMIL (in isoform c)"
FT /id="VSP_061883"
FT MUTAGEN 146
FT /note="C->Y: Embronically lethal."
FT /evidence="ECO:0000269|PubMed:18245374"
FT MUTAGEN 383
FT /note="G->E: In m41; temperature-sensitive. No visible
FT change in dauer formation and adult lifepspan at 15 degrees
FT Celsius, but undergoes dauer formation at 25 degrees
FT Celsius and has increased lifespan. Slight decrease in NaCl
FT avoidance behavior after exposure to NaCl under starvation
FT conditions. Normal number of muscle membrane extensions."
FT /evidence="ECO:0000269|PubMed:11743719,
FT ECO:0000269|PubMed:16950159, ECO:0000269|PubMed:18436204"
FT MUTAGEN 401
FT /note="C->Y: Dauer formation; when associated with L-470."
FT /evidence="ECO:0000269|PubMed:9252323"
FT MUTAGEN 469
FT /note="C->S: Dauer formation above 20 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:9252323"
FT MUTAGEN 470
FT /note="P->L: Dauer formation; when associated with Y-401."
FT /evidence="ECO:0000269|PubMed:9252323"
FT MUTAGEN 547
FT /note="G->S: In m596; increases the number of muscle
FT membrane extensions during larval development."
FT /evidence="ECO:0000269|PubMed:18436204"
FT MUTAGEN 573
FT /note="S->L: In e1368; dauer formation above 25 degrees
FT Celsius. Enhances dauer formation in a tatn-1 RNAi mutant
FT background."
FT /evidence="ECO:0000269|PubMed:24385923,
FT ECO:0000269|PubMed:9252323"
FT MUTAGEN 580
FT /note="A->T: Dauer formation above 26 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:11274053"
FT MUTAGEN 648
FT /note="D->N: Dauer formation above 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:9252323"
FT MUTAGEN 1045
FT /note="C->Y: In m577; normal number of muscle membrane
FT extensions."
FT /evidence="ECO:0000269|PubMed:18436204"
FT MUTAGEN 1374
FT /note="D->N: In sa219; dauer formation above 20 degrees
FT Celsius. Normal NaCl avoidance behavior after exposure to
FT NaCl under starvation conditions."
FT /evidence="ECO:0000269|PubMed:16950159,
FT ECO:0000269|PubMed:9252323"
FT MUTAGEN 1434
FT /note="P->L: In e1391; dauer formation above 20 degrees
FT Celsius and increased lifespan. Increases the number of
FT muscle membrane extensions during larval development."
FT /evidence="ECO:0000269|PubMed:18436204,
FT ECO:0000269|PubMed:24332851, ECO:0000269|PubMed:9252323"
FT MUTAGEN 1465
FT /note="P->S: In e1370; extended lifespan. Accumulates fat
FT and undergoes dauer formation with a developmentally
FT arrested germline at 25 degrees Celsius and above.
FT Pigmented intestine and increased resistance to bacterial
FT pathogens, UV, high temperature and paraquat treatment. At
FT 22 degrees Celsius, under constant darkness conditions only
FT 41% of animals enter the dauer diapause phase, while under
FT constant white light exposure, 100% of animals enter the
FT dauer diapause phase and lifepan increases. Under standard
FT day light conditions 87% of animals lived longer as
FT compared to wild-type. Reduced number of germline
FT progenitors during larval development and proliferation of
FT germline stem cells. Fails to avoid NaCl after exposure to
FT NaCl under starvation conditions. Increases the number of
FT muscle membrane extensions during larval development.
FT Overextension of PML neuron axons. Reduces nucleoli size in
FT hypodermal and pharyngeal muscle cells. Enhances the
FT defective seam cell development and delayed terminal
FT differentiation phenotype of the sea-2 bp283 mutant."
FT /evidence="ECO:0000269|PubMed:11274053,
FT ECO:0000269|PubMed:16950159, ECO:0000269|PubMed:18245374,
FT ECO:0000269|PubMed:18436204, ECO:0000269|PubMed:18782349,
FT ECO:0000269|PubMed:21334311, ECO:0000269|PubMed:21471153,
FT ECO:0000269|PubMed:22278922, ECO:0000269|PubMed:22916022,
FT ECO:0000269|PubMed:23995781, ECO:0000269|PubMed:24332851,
FT ECO:0000269|PubMed:26552888, ECO:0000269|PubMed:28853436,
FT ECO:0000269|PubMed:29500338, ECO:0000269|PubMed:9252323,
FT ECO:0000269|PubMed:9790527"
FT CONFLICT 838
FT /note="H -> R (in Ref. 1; AAC47715)"
FT /evidence="ECO:0000305"
FT CONFLICT 1313
FT /note="K -> Q (in Ref. 1; AAC47715)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1846 AA; 207124 MW; 230B28322FF0F126 CRC64;
MTRMNIVRCR RRHKILENLE EENLGPSCSS TTSTTAATEA LGTTTEDMRL KQQRSSSRAT
EHDIVDGNHH DDEHITMRRL RLVKNSRTRR RTTPDSSMDC YEENPPSQKT SINYSWISKK
SSMTSLMLLL LFAFVQPCAS IVEKRCGPID IRNRPWDIKP QWSKLGDPNE KDLAGQRMVN
CTVVEGSLTI SFVLKHKTKA QEEMHRSLQP RYSQDEFITF PHLREITGTL LVFETEGLVD
LRKIFPNLRV IGGRSLIQHY ALIIYRNPDL EIGLDKLSVI RNGGVRIIDN RKLCYTKTID
WKHLITSSIN DVVVDNAAEY AVTETGLMCP RGACEEDKGE SKCHYLEEKN QEQGVERVQS
CWSNTTCQKS CAYDRLLPTK EIGPGCDANG DRCHDQCVGG CERVNDATAC HACKNVYHKG
KCIEKCDAHL YLLLQRRCVT REQCLQLNPV LSNKTVPIKA TAGLCSDKCP DGYQINPDDH
RECRKCVGKC EIVCEINHVI DTFPKAQAIR LCNIIDGNLT IEIRGKQDSG MASELKDIFA
NIHTITGYLL VRQSSPFISL NMFRNLRRIE AKSLFRNLYA ITVFENPNLK KLFDSTTDLT
LDRGTVSIAN NKMLCFKYIK QLMSKLNIPL DPIDQSEGTN GEKAICEDMA INVSITAVNA
DSVFFSWPSF NITDIDQRKF LGYELFFKEV PRIDENMTIE EDRSACVDSW QSVFKQYYET
SNGEPTPDIF MDIGPRERIR PNTLYAYYVA TQMVLHAGAK NGVSKIGFVR TSYYTPDPPT
LALAQVDSDA IHITWEAPLQ PNGDLTHYTI MWRENEVSPY EEAEKFCTDA STPANRQHTK
DPKETIVADK PVDIPSSRTV APTLLTMMGH EDQQKTCAAT PGCCSCSAIE ESSEQNKKKR
PDPMSAIESS AFENKLLDEV LMPRDTMRVR RSIEDANRVS EELEKAENLG KAPKTLGGKK
PLIHISKKKP SSSSTTSTPA PTIASMYALT RKPTTVPGTR IRLYEIYEPL PGSWAINVSA
LALDNSYVIR NLKHYTLYAI SLSACQNMTV PGASCSISHR AGALKRTKHI TDIDKVLNET
IEWRFMNNSQ QVNVTWDPPT EVNGGIFGYV VKLKSKVDGS IVMTRCVGAK RGYSTRNQGV
LFQNLADGRY FVSVTATSVH GAGPEAESSD PIVVMTPGFF TVEIILGMLL VFLILMSIAG
CIIYYYIQVR YGKKVKALSD FMQLNPEYCV DNKYNADDWE LRQDDVVLGQ QCGEGSFGKV
YLGTGNNVVS LMGDRFGPCA IKINVDDPAS TENLNYLMEA NIMKNFKTNF IVKLYGVIST
VQPAMVVMEM MDLGNLRDYL RSKREDEVFN ETDCNFFDII PRDKFHEWAA QICDGMAYLE
SLKFCHRDLA ARNCMINRDE TVKIGDFGMA RDLFYHDYYK PSGKRMMPVR WMSPESLKDG
KFDSKSDVWS FGVVLYEMVT LGAQPYIGLS NDEVLNYIGM ARKVIKKPEC CENYWYKVMK
MCWRYSPRDR PTFLQLVHLL AAEASPEFRD LSFVLTDNQM ILDDSEALDL DDIDDTDMND
QVVEVAPDVE NVEVQSDSER RNTDSIPLKQ FKTIPPINAT TSHSTISIDE TPMKAKQREG
SLDEEYALMN HSGGPSDAEV RTYAGDGDYV ERDVRENDVP TRRNTGASTS SYTGGGPYCL
TNRGGSNERG AGFGEAVRLT DGVGSGHLND DDYVEKEISS MDTRRSTGAS SSSYGVPQTN
WSGNRGATYY TSKAQQAATA AAAAAAALQQ QQNGGRGDRL TQLPGTGHLQ STRGGQDGDY
IETEPKNYRN NGSPSRNGNS RDIFNGRSAF GENEHLIEDN EHHPLV
//
