INSR_XENLA
ID INSR_XENLA Reviewed; 1362 AA.
AC Q9PVZ4; Q99084;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Insulin receptor;
DE Short=IR;
DE EC=2.7.10.1;
DE AltName: Full=XTK-1b;
DE AltName: Full=Xe-InsR;
DE Contains:
DE RecName: Full=Insulin receptor subunit alpha;
DE Contains:
DE RecName: Full=Insulin receptor subunit beta;
DE Flags: Precursor;
GN Name=insr;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAB46565.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Oocyte {ECO:0000269|PubMed:10446274};
RX PubMed=10446274; DOI=10.1016/s0925-4773(99)00102-1;
RA Groigno L., Richard-Parpaillon L., Boujard D.;
RT "Expression pattern of insulin receptor mRNA during Xenopus laevis
RT embryogenesis.";
RL Mech. Dev. 86:151-154(1999).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAA50006.1, ECO:0000312|PIR:B41122}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1023-1178, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Embryo {ECO:0000269|PubMed:1648732};
RX PubMed=1648732; DOI=10.1073/pnas.88.14.6214;
RA Scavo L.M., Shuldiner A.R., Serrano J., Dashner R., Roth J., de Pablo F.;
RT "Genes encoding receptors for insulin and insulin-like growth factor I are
RT expressed in Xenopus oocytes and embryos.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:6214-6218(1991).
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND AUTOPHOSPHORYLATION.
RX PubMed=1847619; DOI=10.1042/bj2730673;
RA Hainaut P., Kowalski A., Giorgetti S., Baron V., Van Obberghen E.;
RT "Insulin and insulin-like-growth-factor-I (IGF-I) receptors in Xenopus
RT laevis oocytes. Comparison with insulin receptors from liver and muscle.";
RL Biochem. J. 273:673-678(1991).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=7595277; DOI=10.1002/jez.1402730206;
RA Cowan B.J., Foty R.A., Liversage R.A.;
RT "Insulin receptors in Xenopus laevis liver and forelimb regenerates and the
RT effects of local insulin deprivation on regeneration.";
RL J. Exp. Zool. 273:130-141(1995).
CC -!- FUNCTION: Receptor tyrosine kinase which mediates actions of insulin.
CC May be required for forelimb regeneration. {ECO:0000269|PubMed:1847619,
CC ECO:0000269|PubMed:7595277}.
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:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Autophosphorylation activates the kinase activity.
CC {ECO:0000250|UniProtKB:P06213}.
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). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1648732,
CC ECO:0000269|PubMed:7595277}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:1648732, ECO:0000269|PubMed:7595277}.
CC -!- TISSUE SPECIFICITY: Localized mainly to the envelope in oocytes.
CC Localized to the animal hemisphere during early embryonic cleavage.
CC Expressed during organogenesis in regions of ecto- and mesodermic
CC origins. Expressed in the entire encephalon, the otic and optic
CC vesicles, the gills, the somites and the pronephric tubules of the
CC embryo. Also found in adult liver, muscle and regenerated forelimbs.
CC {ECO:0000269|PubMed:10446274, ECO:0000269|PubMed:1847619,
CC ECO:0000269|PubMed:7595277}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Weakly
CC expressed in embryos through gastrulation and neurulation. Expressed in
CC the tailbud stage and in older tadpoles. {ECO:0000269|PubMed:10446274,
CC ECO:0000269|PubMed:1648732}.
CC -!- PTM: Autophosphorylated on tyrosine residues in response to insulin.
CC {ECO:0000269|PubMed:1847619, ECO:0000269|PubMed:7595277}.
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; AJ132556; CAB46565.1; -; mRNA.
DR EMBL; M64660; AAA50006.1; -; mRNA.
DR PIR; B41122; B41122.
DR RefSeq; NP_001081702.1; NM_001088233.1.
DR PRIDE; Q9PVZ4; -.
DR GeneID; 398006; -.
DR KEGG; xla:398006; -.
DR CTD; 398006; -.
DR Xenbase; XB-GENE-920741; insr.L.
DR OrthoDB; 223327at2759; -.
DR Proteomes; UP000186698; Chromosome 1L.
DR Bgee; 398006; Expressed in blastula and 17 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043559; F:insulin binding; IDA:UniProtKB.
DR GO; GO:0005009; F:insulin receptor activity; IDA:UniProtKB.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISS:UniProtKB.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0051425; F:PTB domain binding; IPI:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR CDD; cd00063; FN3; 3.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.60.40.10; -; 4.
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; IPR040969; Insulin_TMD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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 InterPro; IPR016246; Tyr_kinase_insulin-like_rcpt.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF17870; Insulin_TMD; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000620; Insulin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00261; FU; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; SSF49265; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cleavage on pair of basic residues;
KW Developmental protein; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..37
FT /evidence="ECO:0000255"
FT CHAIN 38..754
FT /note="Insulin receptor subunit alpha"
FT /evidence="ECO:0000305"
FT /id="PRO_0000045751"
FT CHAIN 759..1362
FT /note="Insulin receptor subunit beta"
FT /evidence="ECO:0000305"
FT /id="PRO_0000045752"
FT TOPO_DOM 759..951
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 952..972
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 973..1362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 508..629
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 633..730
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 849..944
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1012..1287
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 38..184
FT /note="Leucine-rich region"
FT /evidence="ECO:0000250"
FT REGION 741..749
FT /note="Insulin-binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 1148
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 1022
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1046
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P06213,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1093..1099
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1152..1153
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1166
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 76
FT /note="Insulin-binding"
FT /evidence="ECO:0000250"
FT MOD_RES 993
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1174
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1178
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1179
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1335
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1341
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 642
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 660
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 707
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 779
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 917
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 930
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..63
FT /evidence="ECO:0000250"
FT DISULFID 163..192
FT /evidence="ECO:0000250"
FT DISULFID 196..219
FT /evidence="ECO:0000250"
FT DISULFID 206..225
FT /evidence="ECO:0000250"
FT DISULFID 229..238
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 233..244
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 245..253
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 249..262
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 265..274
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 278..290
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 296..321
FT /evidence="ECO:0000250"
FT DISULFID 303..311
FT /evidence="ECO:0000250"
FT DISULFID 325..338
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 341..345
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 349..370
FT /evidence="ECO:0000250"
FT DISULFID 472..505
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 561
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P06213"
FT DISULFID 683..896
FT /evidence="ECO:0000250"
FT DISULFID 822..830
FT /evidence="ECO:0000250"
SQ SEQUENCE 1362 AA; 153757 MW; 7B8BF2FB7EFDA01B CRC64;
MGQGVLRGEG HPNNNPNSKV GWKSLVGIIT IFMLILCDQS DGKICYSMDI RNNISQFSML
EDCTVIEGHL QILLMFTSKP ENFRGLRFPK LTTITDYLLL FRVYGLESLK DLFPNLTVIR
GTRLFFNYAL VIFEMVHXKE IGLYNLMNIT RGSVRIEKNN ELCYLSTIDW SIILDSVEDN
YIELNRDNKE ECGDVCPGTV KGKSKCKHTL VNGALVERCW TQDHCQKVCP SDCKGSGCLP
DGQCCHPECL GSCRKPNDPS ECTACRHFQN EGVCVTACPK GSYQFQGWRC IDFNTCQELN
SRCQNSRDNS CPPYVIHKGE CMPDCPSGYI ANSTTRTCTP CAGPCPKVCT IFQNVKTIDS
VTSAQELRGC TVINGSLIIN LRGGNNIATE LEANLGLIEE ISGYLKIRRS YALVSLSFFR
KLRLIRGEVL EAGNYSFYAL DNPSLRQLWD WHKHNLTIIH GKLFFHHNPR LCLSQIHQME
EVTGTKGRQD KNDIATKTNG DQASCEDNLL TFNFIKTSHD MVLLRWDAYW PPDYRDLLGF
MVHYKEAPFQ NVTEFDGQDA CGSNSWTVVD MDAPERSADG KTQSPGCLLR SLKPWTQYAV
FVKTLVSGSD EGRTYGAKSK IIYIRTNETI PSVPLDPFSV SNSTSQIILK WKPPSEPNGN
VTHYLVYWQE QPEDSDLYEV DYCNKGLKLP SRTWTPPTEI DENGNENQTE HTSVNKCCPC
PKTEFQIQKE QDESAFRKTF ENYLHNEVFI PRPVRKRRDL FGVANGTLPD PVTAPPLFNV
SSTRAPDEPE PKIYSQKVWF KESVLISGLK HFTGYRIEIH ACNHELSMGC SVAAYVNART
MPEATADKVV GPITYEYVEP NIIHLKWQEP KDPNGLIVLY EVHYSRVGGI EEVITCVSQK
QYNTDKGGKL RVLTPGNYSV KIRATSLAGN GSWTEQAYFQ VPDHPHSNIV KIITGPIIAV
FLLLIVLVYC VVQKKKDAEG PAGPLYTSSN PEYLSASEVY IPDEWEVPRD KINLLRELGQ
GSFGMVYEGI AKDIIKGEPE VRVAVKTVNE SASLRERIEF LNEASVMKAF NCHHVVRLLG
VVSKGQPTLV IMELMAHGDL KSYLRSLRPD AENNPGRLAP TLKEIIQMAA EISDGMAYLN
AKKFVHRDLA ARNCMVADDY AVKIGDFGMT RDIYETDYYR KGGKGLLPVR WMSPESLKDG
VFTAFSDVWS FGVVLWEITS LAEQPYQGLS NEQVLKFVMD GGSLDHPENC PPRLHSLMQM
CWQYNPKMRP TFLEIIDMLK DDLRPSFQDV SFYYSDENKP PETDDLEIDF ENMESTPLDP
SSCSLRDQSS RTNIYEEHIP YTHMNGGRKN GRILSLPRSS PS
