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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 //