ID INSR_CAEEL Reviewed; 1846 AA. AC Q968Y9; B5QS63; O16131; DT 03-NOV-2009, integrated into UniProtKB/Swiss-Prot. DT 03-NOV-2009, sequence version 2. DT 05-JUN-2019, entry version 156. 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 RP MUTAGENESIS OF CYS-401; CYS-469; PRO-470; SER-573; ASP-648; ASP-1374; RP PRO-1434 AND 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 RT diapause 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 RT investigating 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 RP 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 RT 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; RP ASN-1017 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 RT aging and 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 RT through 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 RT Caenorhabditis elegans DAF-2 insulin/IGF-1 receptor."; RL Genetics 178:931-946(2008). RN [12] 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- RT 1/Nrf and DAF-16/FoxO."; RL Cell Metab. 15:713-724(2012). RN [13] 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 [14] RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-1434 AND RP 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 [15] 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., RA Chamberlain G., Yu F., Sun T., Papanicolaou T., Lam A., Yang X., RA Chin-Sang I.; RT "Insulin activates the insulin receptor to downregulate the PTEN RT tumour suppressor."; RL Oncogene 33:3878-3885(2014). RN [16] 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 RT stem cell proliferation to oocyte needs in C. elegans."; RL Development 142:4230-4241(2015). RN [17] 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 [18] 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., RA 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). CC -!- FUNCTION: Insulin receptor-like tyrosine kinase which regulates CC metabolism, controls longevity and prevents developmental arrest CC at the dauer stage (PubMed:9252323, PubMed:9790527, CC PubMed:11743719, PubMed:24332851, PubMed:28853436, CC PubMed:21334311). Binding of INS family members may either CC 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). Required for the response to CC environmental stimuli such as food, pheromone, and temperature CC (PubMed:24332851). Negatively regulates resistance to UV and CC oxidative stress (PubMed:24332851). Role in immune function and CC pathogen resistance (PubMed:18782349). Negatively regulates CC autophagy (PubMed:22560223). Regulates daf-18/PTEN protein levels CC (PubMed:23995781). {ECO:0000269|PubMed:11274053, CC ECO:0000269|PubMed:11743719, ECO:0000269|PubMed:18782349, CC ECO:0000269|PubMed:21334311, ECO:0000269|PubMed:22278922, CC ECO:0000269|PubMed:22560223, ECO:0000269|PubMed:23995781, CC ECO:0000269|PubMed:24332851, ECO:0000269|PubMed:9252323, CC ECO:0000269|PubMed:9790527}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L- CC tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, CC Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; CC EC=2.7.10.1; Evidence={ECO:0000250|UniProtKB:P06213, CC ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305}; CC -!- ACTIVITY REGULATION: Autophosphorylation activates the kinase CC activity (By similarity). Interaction with shc-1 may inhibit its CC activity (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 CC domain) (PubMed:18832074). Interacts (via kinase domain) with daf- CC 18 (via C-terminus) (PubMed:23995781). CC {ECO:0000250|UniProtKB:P06213, ECO:0000269|PubMed:18832074, CC ECO:0000269|PubMed:23995781}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P06213}; CC Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P06213}. CC -!- DISRUPTION PHENOTYPE: Accumulation of fat, pigmented intestine, CC increased lifespan, increased dauer formation and increased CC resistance to pathogens. Severe loss of function mutants display CC recessive early embryonic lethality (PubMed:9252323, CC PubMed:9790527, PubMed:11274053, PubMed:18782349, CC PubMed:18245374). RNAi-mediated knockdown in germline, hypodermis, CC intestine or in muscles causes increased lifespan CC (PubMed:24332851, PubMed:28853436). RNAi-mediated knockdown in a CC ncl-1 mutant (e1942) background reduces the increased longevity of CC the daf-2 single mutant, and reduces the increased ribosomal CC protein synthesis in the ncl-1 single mutant (e1942) CC (PubMed:28853436). RNAi-mediated knockdown in adults causes an CC increase in lgg-1 positive autophagic vesicles (PubMed:22560223). CC RNAi-mediated knockdown results in an increase in the number of CC muscle arm extensions (PubMed:18436204). 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:28853436, ECO:0000269|PubMed:9252323, CC 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 PIR; T42047; T42047. DR RefSeq; NP_497650.4; NM_065249.4. DR BioGrid; 40655; 165. DR STRING; 6239.Y55D5A.5a; -. DR iPTMnet; Q968Y9; -. DR EPD; Q968Y9; -. DR PaxDb; Q968Y9; -. DR PeptideAtlas; Q968Y9; -. DR PRIDE; Q968Y9; -. DR EnsemblMetazoa; Y55D5A.5a.1; Y55D5A.5a.1; WBGene00000898. DR EnsemblMetazoa; Y55D5A.5a.2; Y55D5A.5a.2; WBGene00000898. DR GeneID; 175410; -. DR KEGG; cel:CELE_Y55D5A.5; -. DR CTD; 175410; -. DR WormBase; Y55D5A.5a; CE46852; WBGene00000898; daf-2. DR eggNOG; KOG4258; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00940000170078; -. DR HOGENOM; HOG000151241; -. DR InParanoid; Q968Y9; -. DR KO; K04527; -. DR PhylomeDB; Q968Y9; -. DR Reactome; R-CEL-109704; PI3K Cascade. DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling. DR Reactome; R-CEL-1433557; Signaling by SCF-KIT. DR Reactome; R-CEL-1433559; Regulation of KIT signaling. DR Reactome; R-CEL-186763; Downstream signal transduction. DR Reactome; R-CEL-186797; Signaling by PDGF. DR Reactome; R-CEL-5673001; RAF/MAP kinase cascade. DR Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR SignaLink; Q968Y9; -. DR PRO; PR:Q968Y9; -. DR Proteomes; UP000001940; Chromosome III. DR Bgee; WBGene00000898; Expressed in 5 organ(s), highest expression level in material anatomical entity. 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:0005887; C:integral component of plasma membrane; 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:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0044214; C:spanning component of plasma membrane; IDA:WormBase. DR GO; GO:0005524; F:ATP binding; ISS:WormBase. DR GO; GO:0043560; F:insulin receptor substrate binding; IBA:GO_Central. DR GO; GO:0005009; F:insulin-activated receptor activity; ISS:WormBase. 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:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0005975; P:carbohydrate metabolic process; 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: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: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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central. DR GO; GO:0045887; P:positive regulation of synaptic growth at neuromuscular junction; IGI:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; ISS:WormBase. 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 Gene3D; 2.60.40.10; -; 3. DR Gene3D; 3.80.20.20; -; 2. 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 Pfam; PF00757; Furin-like; 1. DR Pfam; PF07714; Pkinase_Tyr; 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; SSF49265; 2. DR SUPFAM; SSF56112; SSF56112; 1. DR SUPFAM; SSF57184; SSF57184; 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 ATP-binding; Carbohydrate metabolism; KW Cleavage on pair of basic residues; Complete proteome; KW Developmental protein; Disulfide bond; Glycoprotein; Immunity; KW Innate immunity; Kinase; Manganese; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; KW Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase. FT SIGNAL 1 ? {ECO:0000255}. FT CHAIN ? 966 Insulin-like receptor subunit alpha. FT {ECO:0000255}. FT /FTId=PRO_0000386619. FT CHAIN 970 1846 Insulin-like receptor subunit beta. FT {ECO:0000255}. FT /FTId=PRO_0000386620. FT TOPO_DOM 970 1183 Extracellular. {ECO:0000255}. FT TRANSMEM 1184 1204 Helical. {ECO:0000255}. FT TOPO_DOM 1205 1846 Cytoplasmic. {ECO:0000255}. FT DOMAIN 775 869 Fibronectin type-III 1. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 969 1067 Fibronectin type-III 2. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1077 1179 Fibronectin type-III 3. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1246 1528 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 1252 1260 ATP. {ECO:0000250|UniProtKB:P28523, FT ECO:0000255|PROSITE-ProRule:PRU00159}. FT ACT_SITE 1388 1388 Proton acceptor. FT {ECO:0000250|UniProtKB:P28523, FT ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028}. FT BINDING 1282 1282 ATP. {ECO:0000250|UniProtKB:P28523, FT ECO:0000255|PROSITE-ProRule:PRU00159}. FT CARBOHYD 113 113 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 180 180 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 364 364 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:17761667}. FT CARBOHYD 453 453 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:17761667}. FT CARBOHYD 518 518 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 652 652 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 671 671 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 696 696 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:17761667}. FT CARBOHYD 1017 1017 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:17761667}. FT CARBOHYD 1047 1047 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1078 1078 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:17761667}. FT CARBOHYD 1087 1087 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 1093 1093 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 371 386 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 393 401 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 397 410 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 413 422 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 426 438 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 469 483 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 486 490 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 615 646 {ECO:0000250|UniProtKB:P06213}. FT DISULFID 706 706 Interchain. FT {ECO:0000250|UniProtKB:P06213}. FT MUTAGEN 146 146 C->Y: Embronically lethal. FT {ECO:0000269|PubMed:18245374}. FT MUTAGEN 383 383 G->E: In m41; temperature-sensitive. No FT visible change in dauer formation and FT adult lifepspan at 15 degrees Celsius, FT but undergoes dauer formation at 25 FT degrees Celsius and has increased FT lifespan. Slight decrease in NaCl FT avoidance behavior after exposure to NaCl FT under starvation conditions. Normal FT number of muscle membrane extensions. FT {ECO:0000269|PubMed:11743719, FT ECO:0000269|PubMed:16950159, FT ECO:0000269|PubMed:18436204}. FT MUTAGEN 401 401 C->Y: Dauer formation; when associated FT with L-470. {ECO:0000269|PubMed:9252323}. FT MUTAGEN 469 469 C->S: Dauer formation above 20 degrees FT Celsius. {ECO:0000269|PubMed:9252323}. FT MUTAGEN 470 470 P->L: Dauer formation; when associated FT with Y-401. {ECO:0000269|PubMed:9252323}. FT MUTAGEN 547 547 G->S: In m596; increases the number of FT muscle membrane extensions during larval FT development. FT {ECO:0000269|PubMed:18436204}. FT MUTAGEN 573 573 S->L: Dauer formation above 25 degrees FT Celsius. {ECO:0000269|PubMed:9252323}. FT MUTAGEN 580 580 A->T: Dauer formation above 26 degrees FT Celsius. {ECO:0000269|PubMed:11274053}. FT MUTAGEN 648 648 D->N: Dauer formation above 25 degrees FT Celsius. {ECO:0000269|PubMed:9252323}. FT MUTAGEN 1045 1045 C->Y: In m577; normal number of muscle FT membrane extensions. FT {ECO:0000269|PubMed:18436204}. FT MUTAGEN 1374 1374 D->N: In sa219; dauer formation above 20 FT degrees Celsius. Normal NaCl avoidance FT behavior after exposure to NaCl under FT starvation conditions. FT {ECO:0000269|PubMed:16950159, FT ECO:0000269|PubMed:9252323}. FT MUTAGEN 1434 1434 P->L: In e1391; dauer formation above 20 FT degrees Celsius and increased lifespan. FT Increases the number of muscle membrane FT extensions during larval development. FT {ECO:0000269|PubMed:18436204, FT ECO:0000269|PubMed:24332851, FT ECO:0000269|PubMed:9252323}. FT MUTAGEN 1465 1465 P->S: In e1370; extended lifespan. FT Accumulates fat and undergoes dauer FT formation above 25 degrees Celsius. FT Pigmented intestine and increased FT resistance to bacterial pathogens, UV, FT high temperature and paraquat treatment. FT Reduced number of germline progenitors FT during larval development and FT proliferation of germline stem cells. FT Fails to avoid NaCl after exposure to FT NaCl under starvation conditions. FT Increases the number of muscle membrane FT extensions during larval development. FT Overextension of PML neuron axons. FT Reduces nucleoli size in hypodermal and FT pharyngeal muscle cells. FT {ECO:0000269|PubMed:11274053, FT ECO:0000269|PubMed:16950159, FT ECO:0000269|PubMed:18245374, FT ECO:0000269|PubMed:18436204, FT ECO:0000269|PubMed:18782349, FT ECO:0000269|PubMed:21334311, FT ECO:0000269|PubMed:22278922, FT ECO:0000269|PubMed:23995781, FT ECO:0000269|PubMed:24332851, FT ECO:0000269|PubMed:26552888, FT ECO:0000269|PubMed:28853436, FT ECO:0000269|PubMed:9252323, FT ECO:0000269|PubMed:9790527}. FT CONFLICT 838 838 H -> R (in Ref. 1; AAC47715). FT {ECO:0000305}. FT CONFLICT 1313 1313 K -> Q (in Ref. 1; AAC47715). FT {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 //