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INSR_CAEEL
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   03-AUG-2022, entry version 171.
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, 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   [17]
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   [18]
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   [19]
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   [20]
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   [21]
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). Binding of INS family members may either stimulate,
CC       or antagonize, association of the receptor with downstream mediators
CC       such as pdk-1 and age-1 (PubMed:11274053). Required for germline
CC       progenitor proliferation during larval development (PubMed:22278922).
CC       Required 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:23995781,
CC       ECO:0000269|PubMed:24332851, ECO:0000269|PubMed:24385923,
CC       ECO:0000269|PubMed:29500338, ECO:0000269|PubMed:9252323,
CC       ECO:0000269|PubMed:9790527}.
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   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P06213}; Single-
CC       pass type I membrane protein {ECO:0000250|UniProtKB:P06213}.
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   PIR; T42047; T42047.
DR   RefSeq; NP_497650.4; NM_065249.4.
DR   AlphaFoldDB; Q968Y9; -.
DR   SMR; Q968Y9; -.
DR   BioGRID; 40655; 168.
DR   STRING; 6239.Y55D5A.5a; -.
DR   TCDB; 8.A.23.1.30; the basigin (basigin) family.
DR   iPTMnet; Q968Y9; -.
DR   EPD; Q968Y9; -.
DR   PaxDb; Q968Y9; -.
DR   PeptideAtlas; Q968Y9; -.
DR   EnsemblMetazoa; Y55D5A.5a.1; Y55D5A.5a.1; 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   GeneTree; ENSGT00940000170078; -.
DR   HOGENOM; CLU_000288_166_3_1; -.
DR   InParanoid; Q968Y9; -.
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 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: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: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: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: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:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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 assembly 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   CDD; cd00064; FU; 1.
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; IPR006212; Furin_repeat.
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; 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; 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; 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   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 above 25 degrees Celsius.
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:23995781,
FT                   ECO:0000269|PubMed:24332851, ECO:0000269|PubMed:26552888,
FT                   ECO:0000269|PubMed:28853436, ECO:0000269|PubMed:29500338,
FT                   ECO:0000269|PubMed:9252323, 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
 
 
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