IGF1R_XENLA
ID IGF1R_XENLA Reviewed; 1358 AA.
AC O73798;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Insulin-like growth factor 1 receptor;
DE Short=xIGF-1R;
DE Short=xIGFR;
DE EC=2.7.10.1;
DE Contains:
DE RecName: Full=Insulin-like growth factor 1 receptor alpha chain;
DE Contains:
DE RecName: Full=Insulin-like growth factor 1 receptor beta chain;
DE Flags: Precursor;
GN Name=igf1r;
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:AAC12942.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL
RP STAGE, AND AUTOPHOSPHORYLATION.
RC TISSUE=Oocyte {ECO:0000269|PubMed:9492024};
RX PubMed=9492024; DOI=10.1210/endo.139.3.5824;
RA Zhu L., Ohan N., Agazie Y., Cummings C., Farah S., Liu X.J.;
RT "Molecular cloning and characterization of Xenopus insulin-like growth
RT factor-1 receptor: its role in mediating insulin-induced Xenopus oocyte
RT maturation and expression during embryogenesis.";
RL Endocrinology 139:949-954(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, 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 [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=11709186; DOI=10.1016/s1534-5807(01)00069-7;
RA Pera E.M., Wessely O., Li S.-Y., De Robertis E.M.;
RT "Neural and head induction by insulin-like growth factor signals.";
RL Dev. Cell 1:655-665(2001).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11944947; DOI=10.1006/dbio.2002.0605;
RA Richard-Parpaillon L., Heligon C., Chesnel F., Boujard D., Philpott A.;
RT "The IGF pathway regulates head formation by inhibiting Wnt signaling in
RT Xenopus.";
RL Dev. Biol. 244:407-417(2002).
CC -!- FUNCTION: This receptor binds insulin-like growth factor 1 (IGF1) with
CC a high affinity and IGF2 with a lower affinity. It has a tyrosine-
CC protein kinase activity, which is necessary for the activation of the
CC IGF1-stimulated downstream signaling cascade. Plays a role in oocyte
CC maturation. Promotes head development by inhibiting Wnt signaling
CC during embryogenesis. {ECO:0000269|PubMed:11944947,
CC ECO:0000269|PubMed:1847619, ECO:0000269|PubMed:9492024}.
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 ECO:0000269|PubMed:9492024};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Autophosphorylation activates the kinase activity.
CC {ECO:0000250|UniProtKB:P08069}.
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 chain carries the kinase domain (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O73798; Q5HZ83: gipc2.S; NbExp=2; IntAct=EBI-8068109, EBI-8068143;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1847619};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:1847619}.
CC Note=Expressed at the oocyte surface.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Shows
CC biphasic expression during early development. Expressed ubiquitously in
CC fertilized eggs and throughout the midblastula transition. Expression
CC then decreases at mid-gastrulation. Shortly after gastrulation,
CC expression is seen throughout the dorsal side of the embryo with
CC expression strongest in the anterior and absent ventrally. Expression
CC increases along the dorsal midline at early neurulation and is seen in
CC the head region as neurulation progresses, particularly in the area of
CC the cement gland primordium. Also present in the anterior mesoderm but
CC is absent from the neural tube and the most ventral part of the embryo.
CC Remains expressed throughout early embryogenesis. By the tailbud
CC stages, expression is anterior, in the head and the most rostral part
CC of the neural tube. {ECO:0000269|PubMed:11709186,
CC ECO:0000269|PubMed:11944947, ECO:0000269|PubMed:9492024}.
CC -!- PTM: The cytoplasmic domain of the beta subunit is autophosphorylated
CC on Tyr residues in response to low concentrations of insulin-like
CC growth factor (IGF 1) and higher concentrations of insulin.
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; AF055980; AAC12942.1; -; mRNA.
DR RefSeq; NP_001081734.1; NM_001088265.1.
DR AlphaFoldDB; O73798; -.
DR SMR; O73798; -.
DR IntAct; O73798; 1.
DR MINT; O73798; -.
DR GeneID; 398022; -.
DR KEGG; xla:398022; -.
DR CTD; 398022; -.
DR Xenbase; XB-GENE-865040; igf1r.S.
DR OrthoDB; 223327at2759; -.
DR Proteomes; UP000186698; Chromosome 3S.
DR Bgee; 398022; Expressed in ovary and 16 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IC:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISS:UniProtKB.
DR GO; GO:0005520; F:insulin-like growth factor binding; IDA:UniProtKB.
DR GO; GO:0005010; F:insulin-like growth factor receptor activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0005198; F:structural molecule activity; ISS:UniProtKB.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; IEP: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; -; 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; 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; 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; 1.
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; Manganese;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..730
FT /note="Insulin-like growth factor 1 receptor alpha chain"
FT /evidence="ECO:0000303|PubMed:9492024"
FT /id="PRO_0000045749"
FT CHAIN 735..1358
FT /note="Insulin-like growth factor 1 receptor beta chain"
FT /evidence="ECO:0000303|PubMed:9492024"
FT /id="PRO_0000045750"
FT TOPO_DOM 735..934
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 935..955
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 956..1358
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 483..603
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 604..702
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 727..818
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 829..924
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 995..1270
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 670..691
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1336..1358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1131
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P08069,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10028"
FT BINDING 1001..1009
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08069,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1029
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08069,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 976
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1157
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1161
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1162
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 634
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 669
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 741
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 750
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 758
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 895
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 908
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 212..221
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 216..227
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 228..236
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 232..245
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 248..257
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 261..273
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 279..299
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 303..317
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT DISULFID 320..324
FT /evidence="ECO:0000250|UniProtKB:P08069"
SQ SEQUENCE 1358 AA; 153864 MW; 2E4E1F8EA6696776 CRC64;
MKAELVPVCT AWILGLLLCL GPAAAKVCGP NMDIRNDVSE LKQLRDCVVI EGYLQILLIS
NAKAEDFRNL RFPNLTVITD YLLLFRVSGL VSLSNLFPNL TVIRGRVLFY NYALVIFEMT
DLKEIGLYNL RNITRGAVRI EKNSELCYVS TVDWSLVLDA VYNNYIVGNK PPKECVDLCP
GAREKMQICE KSSINNEFAD RCWSDEHCQK VCPSVCGKRA CSDNNECCHP ECLGSCTAPD
NDTACVACHH YFYEGRCVPT CPSNTYKFEG WRCITREVCA KMHIWIHSTI PFIIHKGECV
YECPSGYMLN KSQSMTCSPC EGPCPKICEE KMKTIDSVTS AQMLEGCTVL KGNLQLNIRK
GQNIAAELEN FLGLIETVTG YVKIRHSHAL VSLSFLKSLR YILGEEQMPG NYSFYVFDNN
NLQQLWDWSK HNLTIKEGKI RFAFNSKLCA SEIYRMEEVT GTKGRQAEED ISLSTNGNMA
SCESHVLNFT SRSKIKNRIK LTWERYRPPD YRDLISFTVY YKEAPFRNVT EYDGQDACGS
NSWNMVDVDL PASKESDPGI LLQGLKPWTQ YAIYVKAITL TMLENRHIHG AKSKIIYMRT
DAAVPSIPQD MISASNSSSQ LVVKWNPPSL PNGNLSYYIV RWQQQPQDRH LYQYNYCFKD
KVPNRKYANG TIDTEGGTEP TKPEGSVGEK GHYCACPKTE AEEKAEKDEA EYRKVFENFL
HNSIFVPRPN RRRRDVLAVG NSTVTSYEKN STTEDFSNFS DSERDDIEYP FYETKVDYKW
ERTVISNLQP FTLYRIDIHS CNHEAEKLGC SASNFVFART MPAAGADDIP GIVNTKEEDD
GVIFLGWPEP LRPNGLILMY EIEYKHQGEV HRECVSRQDY RKNGGIKLVR LPPGNYSAQV
QAISLYGNGS WTEMVSFCVK LKPDVRNNIL QMVVAIPLAL SFLLVGIISI VCFVFKKRNS
NRLGNGVLYA SVNPEYFSAA EMYVPDKWEV PREKITMNRE LGQGSFGMVY EGIAKGVVKD
EAETKVAIKT VNEAASMRER IEFLNEASVM KEFNCHHVVR LLGVVSQGQP TLVIMELMTR
GDLKSYLRSL RPDTESNSGQ PTPSLKKMIQ MAGEIADGMS YLNANKFVHR DLAARNCMVT
EDFTVKIGDF GMTRDIYETD YYRKGGKGLL PVRWMSPESL KDGVFTTNSD VWSFGVVLWE
IATLAEQPYQ GMSNEQVLRF VMEGGLLEKP DNCPDMLFEL MRMCWQFNPK MRPSFLEIIS
SIKDELDPGF KEVSFFYSEE NKPPDTEELD LEAENMESIP LDPSCALQNS EHHAGHKSEN
GPGVVVLRAS FDERQPYAHM NGGRKNERAL PLPQSSAC
