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 31-MAY-2011, entry version 82. DE RecName: Full=Insulin-like receptor; DE Short=IR; DE EC=2.7.10.1; DE AltName: Full=Abnormal dauer formation protein 2; DE Contains: DE RecName: Full=Insulin-like receptor subunit alpha; DE Contains: DE RecName: Full=Insulin-like receptor subunit beta; DE Flags: Precursor; GN Name=daf-2; ORFNames=Y55D5A.5; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Nematoda; Chromadorea; Rhabditida; Rhabditoidea; OC Rhabditidae; Peloderinae; Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF CYS-401; CYS-469; PRO-470; SER-573; RP ASP-648; ASP-1374; PRO-1434 AND PRO-1465. RC STRAIN=Bristol N2; RX MEDLINE=97400619; 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] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE RP SPLICING. RC STRAIN=Bristol N2; RX MEDLINE=99069613; 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] 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] 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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-364; ASN-453; ASN-696; RP ASN-1017 AND ASN-1078, AND 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 [6] 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 [7] 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). CC -!- FUNCTION: An insulin receptor-like protein which regulates CC metabolism, controls longevity and prevents developmental arrest CC at the dauer stage. Binding of INS family members may either CC stimulate, or antagonise, association of the receptor with CC downstream mediators such as pdk-1 and age-1. Required for the CC response to environmental stimuli such as food, pheromone, and CC temperature. Role in immune function and pathogen resistance. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- COFACTOR: Manganese (By similarity). CC -!- ENZYME REGULATION: Autophosphorylation activates the kinase CC activity (By similarity). 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). CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a; CC IsoId=Q968Y9-1; Sequence=Displayed; CC Name=b; CC IsoId=Q968Y9-2; Sequence=VSP_053157, VSP_053158; CC Note=No experimental confirmation available; CC -!- DISRUPTION PHENOTYPE: Accumulation of fat, pigmented intestine, CC increased life span, increased dauer formation and increased CC resistance to pathogens. Severe loss of function mutants display CC recessive early embryonic lethality. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Insulin receptor subfamily. CC -!- SIMILARITY: Contains 3 fibronectin type-III domains. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAK29947.2; Type=Erroneous initiation; CC Sequence=ACH98486.1; Type=Erroneous initiation; 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; AC084196; AAK29947.2; ALT_INIT; Genomic_DNA. DR EMBL; AC084196; ACH98486.1; ALT_INIT; Genomic_DNA. DR PIR; T42047; T42047. DR RefSeq; NP_001122734.1; NM_001129262.2. DR RefSeq; NP_497650.3; NM_065249.3. DR UniGene; Cel.8775; -. DR UniGene; Cel.9674; -. DR HSSP; P08069; 1JQH. DR ProteinModelPortal; Q968Y9; -. DR SMR; Q968Y9; 145-658, 768-815, 1026-1171, 1225-1541. DR STRING; Q968Y9; -. DR EnsemblMetazoa; Y55D5A.5a; Y55D5A.5a; Y55D5A.5. DR GeneID; 175410; -. DR KEGG; cel:Y55D5A.5; -. DR CTD; 175410; -. DR WormBase; Y55D5A.5a; CE27499; WBGene00000898; daf-2. DR WormBase; Y55D5A.5b; CE42198; WBGene00000898; daf-2. DR GeneTree; EMGT00050000002732; -. DR PhylomeDB; Q968Y9; -. DR NextBio; 888038; -. DR ArrayExpress; Q968Y9; -. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:EC. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW. DR GO; GO:0043053; P:dauer entry; IMP:WormBase. DR GO; GO:0043054; P:dauer exit; IMP:WormBase. DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0019915; P:lipid storage; IMP:WormBase. DR GO; GO:0040011; P:locomotion; IMP:WormBase. DR GO; GO:0010553; P:negative regulation of gene-specific transcription from RNA polymerase II promoter; IMP:WormBase. DR GO; GO:0042992; P:negative regulation of transcription factor import into nucleus; IMP:WormBase. DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro. DR GO; GO:0000003; P:reproduction; IMP:WormBase. DR GO; GO:0009408; P:response to heat; IMP:WormBase. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro. DR InterPro; IPR000494; EGF_rcpt_L. DR InterPro; IPR008957; Fibronectin_III_dom. DR InterPro; IPR003961; FN_III. DR InterPro; IPR006211; Furin-like_Cys-rich_dom. DR InterPro; IPR009030; Growth_fac_rcpt. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR001245; Ser-Thr/Tyr-Pkinase. DR InterPro; IPR020635; Tyr_Pkinase_cat_dom. DR InterPro; IPR008266; Tyr_prot_kinase_AS. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 4. DR Pfam; PF00041; fn3; 1. 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; FN_III-like; 2. DR SUPFAM; SSF57184; Grow_fac_recept; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR PROSITE; PS50853; FN3; 3. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG. 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; 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; Repeat; Signal; KW Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase. FT SIGNAL 1 ? Potential. FT CHAIN ? 966 Insulin-like receptor subunit alpha. FT /FTId=PRO_0000386619. FT CHAIN 970 1846 Insulin-like receptor subunit beta. FT /FTId=PRO_0000386620. FT TOPO_DOM 970 1183 Extracellular (Potential). FT TRANSMEM 1184 1204 Helical; (Potential). FT TOPO_DOM 1205 1846 Cytoplasmic (Potential). FT DOMAIN 776 862 Fibronectin type-III 1. FT DOMAIN 970 1061 Fibronectin type-III 2. FT DOMAIN 1072 1174 Fibronectin type-III 3. FT DOMAIN 1246 1528 Protein kinase. FT NP_BIND 1252 1260 ATP (By similarity). FT ACT_SITE 1388 1388 Proton acceptor (By similarity). FT BINDING 1282 1282 ATP (By similarity). FT CARBOHYD 113 113 N-linked (GlcNAc...) (Potential). FT CARBOHYD 180 180 N-linked (GlcNAc...) (Potential). FT CARBOHYD 364 364 N-linked (GlcNAc...). FT CARBOHYD 453 453 N-linked (GlcNAc...). FT CARBOHYD 518 518 N-linked (GlcNAc...) (Potential). FT CARBOHYD 652 652 N-linked (GlcNAc...) (Potential). FT CARBOHYD 671 671 N-linked (GlcNAc...) (Potential). FT CARBOHYD 696 696 N-linked (GlcNAc...). FT CARBOHYD 1017 1017 N-linked (GlcNAc...). FT CARBOHYD 1047 1047 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1078 1078 N-linked (GlcNAc...). FT CARBOHYD 1087 1087 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1093 1093 N-linked (GlcNAc...) (Potential). FT DISULFID 371 386 By similarity. FT DISULFID 393 401 By similarity. FT DISULFID 397 410 By similarity. FT DISULFID 413 422 By similarity. FT DISULFID 426 438 By similarity. FT DISULFID 469 483 By similarity. FT DISULFID 486 490 By similarity. FT DISULFID 615 646 By similarity. FT DISULFID 706 706 Interchain (By similarity). FT VAR_SEQ 925 1020 DTMRVRRSIEDANRVSEELEKAENLGKAPKTLGGKKPLIHI FT SKKKPSSSSTTSTPAPTIASMYALTRKPTTVPGTRIRLYEI FT YEPLPGSWAINVSA -> CDIKNDPVGCAMLLLPPEIDDSD FT VGDDDEEPGGGSEQQQRILRNSEILKRQKRQILGRSLGGIH FT GIRSIGRKEYEQFADMILYGNLHDLMMSVMHD (in FT isoform b). FT /FTId=VSP_053157. FT VAR_SEQ 1021 1846 Missing (in isoform b). FT /FTId=VSP_053158. FT MUTAGEN 146 146 C->Y: Embronically lethal. FT MUTAGEN 401 401 C->Y: Dauer formation; when associated FT with L-470. FT MUTAGEN 469 469 C->S: Dauer formation above 20 degrees FT Celsius. FT MUTAGEN 470 470 P->L: Dauer formation; when associated FT with Y-401. FT MUTAGEN 573 573 S->L: Dauer formation above 25 degrees FT Celsius. FT MUTAGEN 580 580 A->T: Dauer formation above 26 degrees FT Celsius. FT MUTAGEN 648 648 D->N: Dauer formation above 25 degrees FT Celsius. FT MUTAGEN 1374 1374 D->N: Dauer formation above 20 degrees FT Celsius. FT MUTAGEN 1434 1434 P->L: Dauer formation above 20 degrees FT Celsius. FT MUTAGEN 1465 1465 P->S: Extended lifespan. Accumulates fat FT and undergoes dauer formation above 25 FT degrees Celsius. Pigmented intestine and FT increased resistance to bacterial FT pathogens. FT CONFLICT 838 838 H -> R (in Ref. 1; AAC47715). FT CONFLICT 1313 1313 K -> Q (in Ref. 1; AAC47715). 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 //