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Protein

Insulin-like growth factor 1 receptor

Gene

IGF1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000140443.13
HGNCiHGNC:5465 IGF1R
MIMi147370 gene
neXtProtiNX_P08069

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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 dbSNP:rs121912426EnsemblClinVar.1
Natural variantiVAR_034892145K → N in IGF1RES; has decreased IGF1R function. 1 PublicationCorresponds to variant dbSNP:rs121912427EnsemblClinVar.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 dbSNP:rs121912429EnsemblClinVar.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 dbSNP:rs141802822EnsemblClinVar.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
DrugBankiDB07474 3-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONE
DB05023 ATL1101
DB05759 IMC-A12
DB05900 INSM-18
DB00047 Insulin Glargine
DB00030 Insulin Human
DB00046 Insulin Lispro
DB00071 Insulin Pork
DB01277 Mecasermin
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB05897 rhIGFBP-3
DB05184 XL228
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...) asparagine1 Publication1
Glycosylationi102N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi135N-linked (GlcNAc...) asparagine1 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...) asparagine1 Publication1
Disulfide bondi251 ↔ 2601 Publication
Disulfide bondi264 ↔ 2761 Publication
Disulfide bondi282 ↔ 3031 Publication
Disulfide bondi307 ↔ 3211 Publication
Glycosylationi314N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi324 ↔ 3281 Publication
Disulfide bondi332 ↔ 3531 Publication
Glycosylationi417N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi438N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi455 ↔ 4881 Publication
Glycosylationi534N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi607N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi622N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi640N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi747N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi756N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi764N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi900N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi913N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi52065

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 Expressed in 233 organ(s), highest expression level in caput epididymis
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). Interacts (nascent precursor form) with ZFAND2B (PubMed:26692333).25 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109701, 101 interactors
CORUMiP08069
DIPiDIP-476N
IntActiP08069, 55 interactors
MINTiP08069
STRINGi9606.ENSP00000268035

Chemistry databases

BindingDBiP08069

Structurei

Secondary structure

11367
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
cd00064 FU, 1 hit
Gene3Di2.60.40.10, 2 hits
3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
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
PfamiView protein in Pfam
PF00757 Furin-like, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PIRSFiPIRSF000620 Insulin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 3 hits
SM00261 FU, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF49265 SSF49265, 4 hits
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS50853 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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J5X1C9J5X1_HUMAN
Tyrosine-protein kinase receptor
IGF1R
1,366Annotation score:
H0YMJ5H0YMJ5_HUMAN
Insulin-like growth factor 1 recept...
IGF1R
190Annotation score:
H0YLE7H0YLE7_HUMAN
Insulin-like growth factor 1 recept...
IGF1R
103Annotation score:
H0YNR0H0YNR0_HUMAN
Insulin-like growth factor 1 recept...
IGF1R
212Annotation score:
H3BSZ8H3BSZ8_HUMAN
Insulin-like growth factor 1 recept...
IGF1R
90Annotation score:

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 dbSNP:rs121912426EnsemblClinVar.1
Natural variantiVAR_034892145K → N in IGF1RES; has decreased IGF1R function. 1 PublicationCorresponds to variant dbSNP:rs121912427EnsemblClinVar.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 → M1 PublicationCorresponds to variant dbSNP:rs45445894Ensembl.1
Natural variantiVAR_034893437R → H1 PublicationCorresponds to variant dbSNP:rs34516635EnsemblClinVar.1
Natural variantiVAR_034894511R → Q. Corresponds to variant dbSNP:rs33958176EnsemblClinVar.1
Natural variantiVAR_041425595R → H1 PublicationCorresponds to variant dbSNP:rs56248469EnsemblClinVar.1
Natural variantiVAR_018856605R → H1 PublicationCorresponds to variant dbSNP:rs45553041Ensembl.1
Natural variantiVAR_034895739R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. 1 PublicationCorresponds to variant dbSNP:rs121912429EnsemblClinVar.1
Natural variantiVAR_034896808H → R. Corresponds to variant dbSNP:rs34061581Ensembl.1
Natural variantiVAR_034897828A → T. Corresponds to variant dbSNP:rs35224135Ensembl.1
Natural variantiVAR_041426857N → S1 PublicationCorresponds to variant dbSNP:rs45611935EnsemblClinVar.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 dbSNP:rs141802822EnsemblClinVar.1
Natural variantiVAR_0414271338A → T1 PublicationCorresponds to variant dbSNP:rs34102392Ensembl.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

Similar proteinsi

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[»]
5U8QX-ray3.27A31-935[»]
5U8RX-ray3.00A31-935[»]
ProteinModelPortaliP08069
SMRiP08069
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109701, 101 interactors
CORUMiP08069
DIPiDIP-476N
IntActiP08069, 55 interactors
MINTiP08069
STRINGi9606.ENSP00000268035

Chemistry databases

BindingDBiP08069
ChEMBLiCHEMBL1957
DrugBankiDB07474 3-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONE
DB05023 ATL1101
DB05759 IMC-A12
DB05900 INSM-18
DB00047 Insulin Glargine
DB00030 Insulin Human
DB00046 Insulin Lispro
DB00071 Insulin Pork
DB01277 Mecasermin
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB05897 rhIGFBP-3
DB05184 XL228
GuidetoPHARMACOLOGYi1801

PTM databases

iPTMnetiP08069
PhosphoSitePlusiP08069

Polymorphism and mutation databases

BioMutaiIGF1R
DMDMi124240

Proteomic databases

EPDiP08069
MaxQBiP08069
PaxDbiP08069
PeptideAtlasiP08069
PRIDEiP08069
ProteomicsDBi52065

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
EuPathDBiHostDB:ENSG00000140443.13
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

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
PROiPR:P08069
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140443 Expressed in 233 organ(s), highest expression level in caput epididymis
CleanExiHS_IGF1R
ExpressionAtlasiP08069 baseline and differential
GenevisibleiP08069 HS

Family and domain databases

CDDicd00063 FN3, 3 hits
cd00064 FU, 1 hit
Gene3Di2.60.40.10, 2 hits
3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
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
PfamiView protein in Pfam
PF00757 Furin-like, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PIRSFiPIRSF000620 Insulin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 3 hits
SM00261 FU, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF49265 SSF49265, 4 hits
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS50853 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
ProtoNetiSearch...

Entry informationi

Entry nameiIGF1R_HUMAN
AccessioniPrimary (citable) accession number: P08069
Secondary accession number(s): B1B5Y2, Q14CV2, Q9UCC0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: September 12, 2018
This is version 217 of the entry and version 1 of the sequence. See 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 chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  8. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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Main funding by: National Institutes of Health

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