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Protein

Insulin-like growth factor 1 receptor

Gene

IGF1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.
When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation10 Publications

Enzyme regulationi

Activated by autophosphorylation at Tyr-1165, Tyr-1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop.11 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1033ATP1
Active sitei1135Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1005 – 1013ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • insulin binding Source: BHF-UCL
  • insulin-like growth factor-activated receptor activity Source: UniProtKB
  • insulin-like growth factor binding Source: UniProtKB
  • insulin-like growth factor I binding Source: UniProtKB
  • insulin receptor binding Source: BHF-UCL
  • insulin receptor substrate binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  • immune response Source: BHF-UCL
  • inactivation of MAPKK activity Source: UniProtKB
  • insulin-like growth factor receptor signaling pathway Source: UniProtKB
  • insulin receptor signaling pathway Source: ProtInc
  • negative regulation of apoptotic process Source: UniProtKB
  • peptidyl-tyrosine autophosphorylation Source: MGI
  • phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • phosphatidylinositol-mediated signaling Source: BHF-UCL
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: ProtInc
  • positive regulation of DNA replication Source: BHF-UCL
  • protein autophosphorylation Source: UniProtKB
  • protein tetramerization Source: UniProtKB
  • regulation of JNK cascade Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06715-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-2404192. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
R-HSA-2428928. IRS-related events triggered by IGF1R.
R-HSA-2428933. SHC-related events triggered by IGF1R.
SignaLinkiP08069.
SIGNORiP08069.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor 1 receptor (EC:2.7.10.1)
Alternative name(s):
Insulin-like growth factor I receptor
Short name:
IGF-I receptor
CD_antigen: CD221
Cleaved into the following 2 chains:
Gene namesi
Name:IGF1R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:5465. IGF1R.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini741 – 935ExtracellularSequence analysisAdd BLAST195
Transmembranei936 – 959HelicalSequence analysisAdd BLAST24
Topological domaini960 – 1367CytoplasmicSequence analysisAdd BLAST408

GO - Cellular componenti

  • alphav-beta3 integrin-IGF-1-IGF1R complex Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: BHF-UCL
  • membrane Source: BHF-UCL
  • plasma membrane Source: AgBase
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Insulin-like growth factor 1 resistance (IGF1RES)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels.
See also OMIM:270450
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034891138R → Q in IGF1RES; has decreased IGF1R function. 1 PublicationCorresponds to variant rs121912426dbSNPEnsembl.1
Natural variantiVAR_034892145K → N in IGF1RES; has decreased IGF1R function. 1 PublicationCorresponds to variant rs121912427dbSNPEnsembl.1
Natural variantiVAR_076247359N → Y in IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts. 1 Publication1
Natural variantiVAR_034895739R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. 1 PublicationCorresponds to variant rs121912429dbSNPEnsembl.1
Natural variantiVAR_076248865Y → C in IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts. 1 Publication1
Natural variantiVAR_0762491256R → S in IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts. 1 Publication1
Natural variantiVAR_0762501337R → C in IGF1RES; a benign mutation or a rare polymorphism, significant decrease in IGF1-induced DNA synthesis; significant increase in IGF1-induced AKT1 phosphorylation in patient fibroblasts. 1 PublicationCorresponds to variant rs141802822dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi980Y → F: Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1, nor with GRB10. 2 Publications1
Mutagenesisi1033K → A: Kinase inactive. Abolishes tyrosine phosphorylation and abolishes interaction with IRS1, SHC1 and PIK3R1. 1 Publication1
Mutagenesisi1280Y → F: No effect on GRB10-binding. 1 Publication1
Mutagenesisi1281Y → F: No effect on GRB10-binding. 1 Publication1
Mutagenesisi1346Y → F: Loss of GRB10-binding. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3480.
MalaCardsiIGF1R.
MIMi270450. phenotype.
OpenTargetsiENSG00000140443.
Orphaneti73273. Growth delay due to insulin-like growth factor I resistance.
PharmGKBiPA29698.

Chemistry databases

ChEMBLiCHEMBL1957.
DrugBankiDB00047. Insulin Glargine.
DB00046. Insulin Lispro.
DB00030. Insulin Regular.
DB01277. Mecasermin.
GuidetoPHARMACOLOGYi1801.

Polymorphism and mutation databases

BioMutaiIGF1R.
DMDMi124240.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 302 PublicationsAdd BLAST30
ChainiPRO_000001668131 – 736Insulin-like growth factor 1 receptor alpha chainAdd BLAST706
ChainiPRO_0000016682741 – 1367Insulin-like growth factor 1 receptor beta chainAdd BLAST627

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 521 Publication
Glycosylationi51N-linked (GlcNAc...)1 Publication1
Glycosylationi102N-linked (GlcNAc...)Sequence analysis1
Glycosylationi135N-linked (GlcNAc...)1 Publication1
Disulfide bondi150 ↔ 1781 Publication
Disulfide bondi182 ↔ 2051 Publication
Disulfide bondi192 ↔ 2111 Publication
Disulfide bondi215 ↔ 2241 Publication
Disulfide bondi219 ↔ 2301 Publication
Disulfide bondi231 ↔ 2391 Publication
Disulfide bondi235 ↔ 2481 Publication
Glycosylationi244N-linked (GlcNAc...)1 Publication1
Disulfide bondi251 ↔ 2601 Publication
Disulfide bondi264 ↔ 2761 Publication
Disulfide bondi282 ↔ 3031 Publication
Disulfide bondi307 ↔ 3211 Publication
Glycosylationi314N-linked (GlcNAc...)1 Publication1
Disulfide bondi324 ↔ 3281 Publication
Disulfide bondi332 ↔ 3531 Publication
Glycosylationi417N-linked (GlcNAc...)Sequence analysis1
Glycosylationi438N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi455 ↔ 4881 Publication
Glycosylationi534N-linked (GlcNAc...)Sequence analysis1
Glycosylationi607N-linked (GlcNAc...)Sequence analysis1
Glycosylationi622N-linked (GlcNAc...)Sequence analysis1
Glycosylationi640N-linked (GlcNAc...)Sequence analysis1
Glycosylationi747N-linked (GlcNAc...)Sequence analysis1
Glycosylationi756N-linked (GlcNAc...)Sequence analysis1
Glycosylationi764N-linked (GlcNAc...)Sequence analysis1
Glycosylationi900N-linked (GlcNAc...)Sequence analysis1
Glycosylationi913N-linked (GlcNAc...)Sequence analysis1
Modified residuei980Phosphotyrosine1 Publication1
Modified residuei1161Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei1165Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei1166Phosphotyrosine; by autocatalysis3 Publications1
Cross-linki1168Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1171Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei1278Phosphoserine; by GSK3-betaBy similarity1
Modified residuei1282PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282. Dephosphorylated by PTPN1 (By similarity).By similarity
Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation.6 Publications
Sumoylated with SUMO1.1 Publication
Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP08069.
MaxQBiP08069.
PaxDbiP08069.
PeptideAtlasiP08069.
PRIDEiP08069.

PTM databases

iPTMnetiP08069.
PhosphoSitePlusiP08069.

Expressioni

Tissue specificityi

Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney.4 Publications

Gene expression databases

BgeeiENSG00000140443.
CleanExiHS_IGF1R.
ExpressionAtlasiP08069. baseline and differential.
GenevisibleiP08069. HS.

Organism-specific databases

HPAiCAB010268.
HPA045563.

Interactioni

Subunit structurei

Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3. Found in a ternary complex with IGF1 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:19578119, PubMed:22351760).24 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-475981,EBI-475981
ARHGEF12Q9NZN57EBI-475981,EBI-821440
CAMPP499133EBI-475981,EBI-6378485
CrkQ640103EBI-475981,EBI-2906540From a different organism.
CSKP412405EBI-475981,EBI-1380630
CTNNB1P352223EBI-475981,EBI-491549
IGF1P050195EBI-475981,EBI-7902275
INSP013174EBI-475981,EBI-3989070From a different organism.
KCNIP3Q9Y2W75EBI-475981,EBI-751501
LEF1Q9UJU25EBI-475981,EBI-926131
MDM2Q009872EBI-475981,EBI-389668
PIK3R1P279864EBI-475981,EBI-79464
PTPN1P180313EBI-475981,EBI-968788
PTPN11Q061243EBI-475981,EBI-297779
SHC1P29353-22EBI-475981,EBI-1000553
TAGLNQ019952EBI-475981,EBI-1054248

GO - Molecular functioni

  • insulin binding Source: BHF-UCL
  • insulin-like growth factor binding Source: UniProtKB
  • insulin-like growth factor I binding Source: UniProtKB
  • insulin receptor binding Source: BHF-UCL
  • insulin receptor substrate binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109701. 71 interactors.
DIPiDIP-476N.
IntActiP08069. 54 interactors.
MINTiMINT-85902.
STRINGi9606.ENSP00000268035.

Chemistry databases

BindingDBiP08069.

Structurei

Secondary structure

11367
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi37 – 41Combined sources5
Helixi43 – 49Combined sources7
Beta strandi53 – 57Combined sources5
Beta strandi59 – 65Combined sources7
Beta strandi68 – 70Combined sources3
Beta strandi80 – 83Combined sources4
Beta strandi85 – 92Combined sources8
Helixi96 – 98Combined sources3
Beta strandi115 – 121Combined sources7
Beta strandi138 – 144Combined sources7
Helixi157 – 160Combined sources4
Helixi164 – 166Combined sources3
Beta strandi168 – 171Combined sources4
Helixi175 – 178Combined sources4
Turni183 – 188Combined sources6
Beta strandi194 – 199Combined sources6
Beta strandi201 – 203Combined sources3
Beta strandi205 – 209Combined sources5
Helixi217 – 219Combined sources3
Beta strandi235 – 241Combined sources7
Beta strandi247 – 255Combined sources9
Beta strandi257 – 263Combined sources7
Beta strandi269 – 271Combined sources3
Turni272 – 274Combined sources3
Beta strandi275 – 277Combined sources3
Helixi279 – 283Combined sources5
Beta strandi297 – 299Combined sources3
Beta strandi302 – 306Combined sources5
Beta strandi311 – 315Combined sources5
Beta strandi321 – 323Combined sources3
Beta strandi325 – 327Combined sources3
Beta strandi331 – 341Combined sources11
Helixi345 – 347Combined sources3
Turni349 – 352Combined sources4
Beta strandi354 – 362Combined sources9
Helixi375 – 378Combined sources4
Beta strandi383 – 386Combined sources4
Beta strandi388 – 392Combined sources5
Turni415 – 417Combined sources3
Beta strandi418 – 423Combined sources6
Turni434 – 436Combined sources3
Beta strandi440 – 443Combined sources4
Beta strandi445 – 451Combined sources7
Helixi456 – 466Combined sources11
Beta strandi474 – 477Combined sources4
Turni479 – 481Combined sources3
Helixi724 – 730Combined sources7
Beta strandi980 – 982Combined sources3
Helixi983 – 985Combined sources3
Turni990 – 992Combined sources3
Helixi996 – 998Combined sources3
Beta strandi999 – 1007Combined sources9
Beta strandi1009 – 1022Combined sources14
Beta strandi1025 – 1034Combined sources10
Beta strandi1037 – 1039Combined sources3
Helixi1041 – 1053Combined sources13
Helixi1054 – 1056Combined sources3
Beta strandi1065 – 1069Combined sources5
Beta strandi1071 – 1074Combined sources4
Beta strandi1076 – 1080Combined sources5
Helixi1087 – 1100Combined sources14
Helixi1109 – 1128Combined sources20
Helixi1138 – 1140Combined sources3
Beta strandi1141 – 1143Combined sources3
Beta strandi1149 – 1151Combined sources3
Helixi1155 – 1157Combined sources3
Helixi1159 – 1164Combined sources6
Turni1165 – 1167Combined sources3
Helixi1168 – 1170Combined sources3
Beta strandi1171 – 1174Combined sources4
Helixi1176 – 1178Combined sources3
Helixi1181 – 1186Combined sources6
Helixi1191 – 1207Combined sources17
Turni1212 – 1215Combined sources4
Helixi1218 – 1226Combined sources9
Helixi1239 – 1248Combined sources10
Helixi1253 – 1255Combined sources3
Helixi1259 – 1266Combined sources8
Helixi1267 – 1269Combined sources3
Helixi1274 – 1277Combined sources4
Turni1279 – 1281Combined sources3
Turni1283 – 1285Combined sources3
Beta strandi1286 – 1288Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IGRX-ray2.60A31-492[»]
1JQHX-ray2.10A/B/C979-1286[»]
1K3AX-ray2.10A988-1286[»]
1M7NX-ray2.70A/B974-1294[»]
1P4OX-ray1.50A/B974-1294[»]
2OJ9X-ray2.00A982-1286[»]
2ZM3X-ray2.50A/B/C/D981-1286[»]
3D94X-ray2.30A986-1286[»]
3F5PX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T981-1286[»]
3I81X-ray2.08A982-1286[»]
3LVPX-ray3.00A/B/C/D951-1286[»]
3LW0X-ray1.79A/B/C/D983-1286[»]
3NW5X-ray2.14A982-1286[»]
3NW6X-ray2.20A982-1286[»]
3NW7X-ray2.11A982-1286[»]
3O23X-ray2.10A982-1286[»]
3QQUX-ray2.90A/B/C/D988-1286[»]
4D2RX-ray2.10A985-1286[»]
4XSSX-ray3.00F721-736[»]
5FXQX-ray2.30A980-1286[»]
5FXRX-ray2.40A980-1286[»]
5FXSX-ray1.90A980-1286[»]
5HZNX-ray2.20A/B/C/D/E/F/G/H983-1286[»]
ProteinModelPortaliP08069.
SMRiP08069.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08069.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini491 – 609Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST119
Domaini610 – 708Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST99
Domaini735 – 828Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST94
Domaini834 – 927Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST94
Domaini999 – 1274Protein kinasePROSITE-ProRule annotationAdd BLAST276

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi977 – 980IRS1- and SHC1-binding4

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
Contains 4 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4258. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000038045.
HOVERGENiHBG006134.
InParanoidiP08069.
KOiK05087.
OMAiGYLYRHN.
OrthoDBiEOG091G00GE.
PhylomeDBiP08069.
TreeFamiTF351636.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProiIPR003961. FN3_dom.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000620. Insulin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
SSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS50853. FN3. 4 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08069-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE
60 70 80 90 100
NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF
110 120 130 140 150
PNLTVIRGWK LFYNYALVIF EMTNLKDIGL YNLRNITRGA IRIEKNADLC
160 170 180 190 200
YLSTVDWSLI LDAVSNNYIV GNKPPKECGD LCPGTMEEKP MCEKTTINNE
210 220 230 240 250
YNYRCWTTNR CQKMCPSTCG KRACTENNEC CHPECLGSCS APDNDTACVA
260 270 280 290 300
CRHYYYAGVC VPACPPNTYR FEGWRCVDRD FCANILSAES SDSEGFVIHD
310 320 330 340 350
GECMQECPSG FIRNGSQSMY CIPCEGPCPK VCEEEKKTKT IDSVTSAQML
360 370 380 390 400
QGCTIFKGNL LINIRRGNNI ASELENFMGL IEVVTGYVKI RHSHALVSLS
410 420 430 440 450
FLKNLRLILG EEQLEGNYSF YVLDNQNLQQ LWDWDHRNLT IKAGKMYFAF
460 470 480 490 500
NPKLCVSEIY RMEEVTGTKG RQSKGDINTR NNGERASCES DVLHFTSTTT
510 520 530 540 550
SKNRIIITWH RYRPPDYRDL ISFTVYYKEA PFKNVTEYDG QDACGSNSWN
560 570 580 590 600
MVDVDLPPNK DVEPGILLHG LKPWTQYAVY VKAVTLTMVE NDHIRGAKSE
610 620 630 640 650
ILYIRTNASV PSIPLDVLSA SNSSSQLIVK WNPPSLPNGN LSYYIVRWQR
660 670 680 690 700
QPQDGYLYRH NYCSKDKIPI RKYADGTIDI EEVTENPKTE VCGGEKGPCC
710 720 730 740 750
ACPKTEAEKQ AEKEEAEYRK VFENFLHNSI FVPRPERKRR DVMQVANTTM
760 770 780 790 800
SSRSRNTTAA DTYNITDPEE LETEYPFFES RVDNKERTVI SNLRPFTLYR
810 820 830 840 850
IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW EPRPENSIFL
860 870 880 890 900
KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN
910 920 930 940 950
YTARIQATSL SGNGSWTDPV FFYVQAKTGY ENFIHLIIAL PVAVLLIVGG
960 970 980 990 1000
LVIMLYVFHR KRNNSRLGNG VLYASVNPEY FSAADVYVPD EWEVAREKIT
1010 1020 1030 1040 1050
MSRELGQGSF GMVYEGVAKG VVKDEPETRV AIKTVNEAAS MRERIEFLNE
1060 1070 1080 1090 1100
ASVMKEFNCH HVVRLLGVVS QGQPTLVIME LMTRGDLKSY LRSLRPEMEN
1110 1120 1130 1140 1150
NPVLAPPSLS KMIQMAGEIA DGMAYLNANK FVHRDLAARN CMVAEDFTVK
1160 1170 1180 1190 1200
IGDFGMTRDI YETDYYRKGG KGLLPVRWMS PESLKDGVFT TYSDVWSFGV
1210 1220 1230 1240 1250
VLWEIATLAE QPYQGLSNEQ VLRFVMEGGL LDKPDNCPDM LFELMRMCWQ
1260 1270 1280 1290 1300
YNPKMRPSFL EIISSIKEEM EPGFREVSFY YSEENKLPEP EELDLEPENM
1310 1320 1330 1340 1350
ESVPLDPSAS SSSLPLPDRH SGHKAENGPG PGVLVLRASF DERQPYAHMN
1360
GGRKNERALP LPQSSTC
Length:1,367
Mass (Da):154,793
Last modified:August 1, 1988 - v1
Checksum:iAE8A735F87F745C8
GO

Sequence cautioni

The sequence BAG11657 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti928 – 929TG → R in BAG11657 (Ref. 3) Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041424105V → L in a renal chromophobe sample; somatic mutation. 1 Publication1
Natural variantiVAR_034891138R → Q in IGF1RES; has decreased IGF1R function. 1 PublicationCorresponds to variant rs121912426dbSNPEnsembl.1
Natural variantiVAR_034892145K → N in IGF1RES; has decreased IGF1R function. 1 PublicationCorresponds to variant rs121912427dbSNPEnsembl.1
Natural variantiVAR_076247359N → Y in IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts. 1 Publication1
Natural variantiVAR_018855388V → M.1 PublicationCorresponds to variant rs45445894dbSNPEnsembl.1
Natural variantiVAR_034893437R → H.1 PublicationCorresponds to variant rs34516635dbSNPEnsembl.1
Natural variantiVAR_034894511R → Q.Corresponds to variant rs33958176dbSNPEnsembl.1
Natural variantiVAR_041425595R → H.1 PublicationCorresponds to variant rs56248469dbSNPEnsembl.1
Natural variantiVAR_018856605R → H.1 PublicationCorresponds to variant rs45553041dbSNPEnsembl.1
Natural variantiVAR_034895739R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. 1 PublicationCorresponds to variant rs121912429dbSNPEnsembl.1
Natural variantiVAR_034896808H → R.Corresponds to variant rs34061581dbSNPEnsembl.1
Natural variantiVAR_034897828A → T.Corresponds to variant rs35224135dbSNPEnsembl.1
Natural variantiVAR_041426857N → S.1 PublicationCorresponds to variant rs45611935dbSNPEnsembl.1
Natural variantiVAR_076248865Y → C in IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts. 1 Publication1
Natural variantiVAR_0762491256R → S in IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts. 1 Publication1
Natural variantiVAR_0762501337R → C in IGF1RES; a benign mutation or a rare polymorphism, significant decrease in IGF1-induced DNA synthesis; significant increase in IGF1-induced AKT1 phosphorylation in patient fibroblasts. 1 PublicationCorresponds to variant rs141802822dbSNPEnsembl.1
Natural variantiVAR_0414271338A → T.1 PublicationCorresponds to variant rs34102392dbSNPEnsembl.1
Natural variantiVAR_0414281347A → V in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04434 mRNA. Translation: CAA28030.1.
AB425196 mRNA. Translation: BAG11657.1. Different initiation.
AY332722 Genomic DNA. Translation: AAP81165.1.
AC055807 Genomic DNA. No translation available.
AC069029 Genomic DNA. No translation available.
AC118658 Genomic DNA. No translation available.
AC118660 Genomic DNA. No translation available.
BC113610 mRNA. Translation: AAI13611.1.
BC113612 mRNA. Translation: AAI13613.1.
M69229 Genomic DNA. Translation: AAB59399.1.
CCDSiCCDS10378.1.
PIRiA25690. IGHUR1.
RefSeqiNP_000866.1. NM_000875.4.
NP_001278787.1. NM_001291858.1.
UniGeneiHs.643120.
Hs.714012.

Genome annotation databases

EnsembliENST00000268035; ENSP00000268035; ENSG00000140443.
GeneIDi3480.
KEGGihsa:3480.
UCSCiuc002bul.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Wikipedia

IGF-1 receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04434 mRNA. Translation: CAA28030.1.
AB425196 mRNA. Translation: BAG11657.1. Different initiation.
AY332722 Genomic DNA. Translation: AAP81165.1.
AC055807 Genomic DNA. No translation available.
AC069029 Genomic DNA. No translation available.
AC118658 Genomic DNA. No translation available.
AC118660 Genomic DNA. No translation available.
BC113610 mRNA. Translation: AAI13611.1.
BC113612 mRNA. Translation: AAI13613.1.
M69229 Genomic DNA. Translation: AAB59399.1.
CCDSiCCDS10378.1.
PIRiA25690. IGHUR1.
RefSeqiNP_000866.1. NM_000875.4.
NP_001278787.1. NM_001291858.1.
UniGeneiHs.643120.
Hs.714012.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IGRX-ray2.60A31-492[»]
1JQHX-ray2.10A/B/C979-1286[»]
1K3AX-ray2.10A988-1286[»]
1M7NX-ray2.70A/B974-1294[»]
1P4OX-ray1.50A/B974-1294[»]
2OJ9X-ray2.00A982-1286[»]
2ZM3X-ray2.50A/B/C/D981-1286[»]
3D94X-ray2.30A986-1286[»]
3F5PX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T981-1286[»]
3I81X-ray2.08A982-1286[»]
3LVPX-ray3.00A/B/C/D951-1286[»]
3LW0X-ray1.79A/B/C/D983-1286[»]
3NW5X-ray2.14A982-1286[»]
3NW6X-ray2.20A982-1286[»]
3NW7X-ray2.11A982-1286[»]
3O23X-ray2.10A982-1286[»]
3QQUX-ray2.90A/B/C/D988-1286[»]
4D2RX-ray2.10A985-1286[»]
4XSSX-ray3.00F721-736[»]
5FXQX-ray2.30A980-1286[»]
5FXRX-ray2.40A980-1286[»]
5FXSX-ray1.90A980-1286[»]
5HZNX-ray2.20A/B/C/D/E/F/G/H983-1286[»]
ProteinModelPortaliP08069.
SMRiP08069.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109701. 71 interactors.
DIPiDIP-476N.
IntActiP08069. 54 interactors.
MINTiMINT-85902.
STRINGi9606.ENSP00000268035.

Chemistry databases

BindingDBiP08069.
ChEMBLiCHEMBL1957.
DrugBankiDB00047. Insulin Glargine.
DB00046. Insulin Lispro.
DB00030. Insulin Regular.
DB01277. Mecasermin.
GuidetoPHARMACOLOGYi1801.

PTM databases

iPTMnetiP08069.
PhosphoSitePlusiP08069.

Polymorphism and mutation databases

BioMutaiIGF1R.
DMDMi124240.

Proteomic databases

EPDiP08069.
MaxQBiP08069.
PaxDbiP08069.
PeptideAtlasiP08069.
PRIDEiP08069.

Protocols and materials databases

DNASUi3480.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000268035; ENSP00000268035; ENSG00000140443.
GeneIDi3480.
KEGGihsa:3480.
UCSCiuc002bul.4. human.

Organism-specific databases

CTDi3480.
DisGeNETi3480.
GeneCardsiIGF1R.
HGNCiHGNC:5465. IGF1R.
HPAiCAB010268.
HPA045563.
MalaCardsiIGF1R.
MIMi147370. gene.
270450. phenotype.
neXtProtiNX_P08069.
OpenTargetsiENSG00000140443.
Orphaneti73273. Growth delay due to insulin-like growth factor I resistance.
PharmGKBiPA29698.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4258. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000038045.
HOVERGENiHBG006134.
InParanoidiP08069.
KOiK05087.
OMAiGYLYRHN.
OrthoDBiEOG091G00GE.
PhylomeDBiP08069.
TreeFamiTF351636.

Enzyme and pathway databases

BioCyciZFISH:HS06715-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-2404192. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
R-HSA-2428928. IRS-related events triggered by IGF1R.
R-HSA-2428933. SHC-related events triggered by IGF1R.
SignaLinkiP08069.
SIGNORiP08069.

Miscellaneous databases

ChiTaRSiIGF1R. human.
EvolutionaryTraceiP08069.
GeneWikiiInsulin-like_growth_factor_1_receptor.
GenomeRNAii3480.
PROiP08069.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140443.
CleanExiHS_IGF1R.
ExpressionAtlasiP08069. baseline and differential.
GenevisibleiP08069. HS.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProiIPR003961. FN3_dom.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000620. Insulin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
SSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS50853. FN3. 4 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIGF1R_HUMAN
AccessioniPrimary (citable) accession number: P08069
Secondary accession number(s): B1B5Y2, Q14CV2, Q9UCC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: November 30, 2016
This is version 200 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.