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P08069 (IGF1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 173. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:IGF1R
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1367 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.10 Ref.11 Ref.12 Ref.19 Ref.23 Ref.25 Ref.27 Ref.32

When present in a hybrid receptor with INSR, binds IGF1. Ref.25 shows that hybrid receptors composed of IGF1R and INSR isoform Longare 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 Shortare activated by IGF1, IGF2 and insulin. In contrast, Ref.32 shows that hybrid receptors composed of IGF1R and INSR isoform Longand hybrid receptors composed of IGF1R and INSR isoform Shorthave similar binding characteristics, both bind IGF1 and have a low affinity for insulin. Ref.8 Ref.10 Ref.11 Ref.12 Ref.19 Ref.23 Ref.25 Ref.27 Ref.32

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.12 Ref.41 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.53 Ref.54

Enzyme regulation

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. Ref.29 Ref.41 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54

Subunit structure

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 GNB2L1/RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3. Ref.10 Ref.13 Ref.15 Ref.17 Ref.18 Ref.20 Ref.21 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.47

Subcellular location

Cell membrane; Single-pass type I membrane protein Ref.33.

Tissue specificity

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. Ref.9 Ref.14 Ref.16 Ref.24

Post-translational modification

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. Ref.10 Ref.12 Ref.13 Ref.22 Ref.41 Ref.42 Ref.46 Ref.47 Ref.48 Ref.52

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.

Sumoylated with SUMO1. Ref.37

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.

Involvement in disease

Insulin-like growth factor 1 resistance (IGF1RES) [MIM:270450]: A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.55 Ref.56

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 4 fibronectin type-III domains.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAG11657.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaxonogenesis

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

establishment of cell polarity

Inferred from electronic annotation. Source: Ensembl

exocrine pancreas development

Inferred from electronic annotation. Source: Ensembl

immune response

Inferred from mutant phenotype PubMed 16886151. Source: BHF-UCL

inactivation of MAPKK activity

Inferred from direct assay Ref.27. Source: UniProtKB

insulin receptor signaling pathway

Traceable author statement PubMed 10829031. Source: ProtInc

insulin-like growth factor receptor signaling pathway

Inferred from direct assay Ref.12. Source: UniProtKB

male sex determination

Inferred from electronic annotation. Source: Ensembl

mammary gland development

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from direct assay Ref.27. Source: UniProtKB

negative regulation of muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine autophosphorylation

Inferred from mutant phenotype PubMed 19545541. Source: MGI

phosphatidylinositol 3-kinase signaling

Inferred by curator Ref.13. Source: BHF-UCL

phosphatidylinositol-mediated signaling

Inferred from direct assay PubMed 7692086. Source: BHF-UCL

positive regulation of DNA replication

Inferred from mutant phenotype Ref.25. Source: BHF-UCL

positive regulation of MAPK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from mutant phenotype Ref.25. Source: BHF-UCL

positive regulation of cell proliferation

Traceable author statement PubMed 10749889. Source: ProtInc

positive regulation of cytokinesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of steroid hormone biosynthetic process

Inferred from electronic annotation. Source: Ensembl

prostate gland epithelium morphogenesis

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay Ref.22Ref.10Ref.12. Source: UniProtKB

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein tetramerization

Inferred from direct assay Ref.10. Source: UniProtKB

regulation of JNK cascade

Inferred from direct assay Ref.27. Source: UniProtKB

response to vitamin E

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 3003744. Source: ProtInc

   Cellular_componentcaveola

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred by curator Ref.12. Source: UniProtKB

intracellular membrane-bounded organelle

Inferred from direct assay Ref.11. Source: BHF-UCL

membrane

Inferred from direct assay Ref.11. Source: BHF-UCL

neuron projection

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction PubMed 11448933PubMed 17586502. Source: IntAct

insulin binding

Inferred from physical interaction Ref.11. Source: BHF-UCL

insulin receptor binding

Inferred from direct assay Ref.11. Source: BHF-UCL

insulin receptor substrate binding

Inferred from physical interaction Ref.13. Source: UniProtKB

insulin-like growth factor I binding

Inferred from physical interaction Ref.11. Source: BHF-UCL

insulin-like growth factor binding

Inferred from direct assay Ref.10Ref.12. Source: UniProtKB

insulin-like growth factor-activated receptor activity

Inferred from direct assay Ref.12. Source: UniProtKB

phosphatidylinositol 3-kinase binding

Inferred from physical interaction Ref.13. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12482592Ref.27Ref.30Ref.31Ref.13Ref.17. Source: UniProtKB

protein tyrosine kinase activity

Inferred from direct assay Ref.22Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Ref.1 Ref.8
Chain31 – 736706Insulin-like growth factor 1 receptor alpha chain
PRO_0000016681
Chain741 – 1367627Insulin-like growth factor 1 receptor beta chain
PRO_0000016682

Regions

Topological domain741 – 935195Extracellular Potential
Transmembrane936 – 95924Helical; Potential
Topological domain960 – 1367408Cytoplasmic Potential
Domain491 – 609119Fibronectin type-III 1
Domain610 – 70899Fibronectin type-III 2
Domain735 – 82894Fibronectin type-III 3
Domain834 – 92794Fibronectin type-III 4
Domain999 – 1274276Protein kinase
Nucleotide binding1005 – 10139ATP By similarity
Motif977 – 9804IRS1- and SHC1-binding

Sites

Active site11351Proton acceptor By similarity
Binding site10331ATP

Amino acid modifications

Modified residue9801Phosphotyrosine Probable
Modified residue11611Phosphotyrosine; by autocatalysis Ref.41 Ref.46 Ref.48
Modified residue11651Phosphotyrosine; by autocatalysis Ref.41 Ref.46 Ref.48
Modified residue11661Phosphotyrosine; by autocatalysis Ref.41 Ref.46 Ref.48
Modified residue12781Phosphoserine; by GSK3-beta By similarity
Modified residue12821Phosphoserine By similarity
Glycosylation511N-linked (GlcNAc...) Ref.40
Glycosylation1021N-linked (GlcNAc...) Potential
Glycosylation1351N-linked (GlcNAc...) Ref.40
Glycosylation2441N-linked (GlcNAc...) Ref.40
Glycosylation3141N-linked (GlcNAc...) Ref.40
Glycosylation4171N-linked (GlcNAc...) Potential
Glycosylation4381N-linked (GlcNAc...) Potential
Glycosylation5341N-linked (GlcNAc...) Potential
Glycosylation6071N-linked (GlcNAc...) Potential
Glycosylation6221N-linked (GlcNAc...) Potential
Glycosylation6401N-linked (GlcNAc...) Potential
Glycosylation7471N-linked (GlcNAc...) Potential
Glycosylation7561N-linked (GlcNAc...) Potential
Glycosylation7641N-linked (GlcNAc...) Potential
Glycosylation9001N-linked (GlcNAc...) Potential
Glycosylation9131N-linked (GlcNAc...) Potential
Disulfide bond33 ↔ 52 Ref.40
Disulfide bond150 ↔ 178 Ref.40
Disulfide bond182 ↔ 205 Ref.40
Disulfide bond192 ↔ 211 Ref.40
Disulfide bond215 ↔ 224 Ref.40
Disulfide bond219 ↔ 230 Ref.40
Disulfide bond231 ↔ 239 Ref.40
Disulfide bond235 ↔ 248 Ref.40
Disulfide bond251 ↔ 260 Ref.40
Disulfide bond264 ↔ 276 Ref.40
Disulfide bond282 ↔ 303 Ref.40
Disulfide bond307 ↔ 321 Ref.40
Disulfide bond324 ↔ 328 Ref.40
Disulfide bond332 ↔ 353 Ref.40
Disulfide bond455 ↔ 488 Ref.40
Cross-link1168Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.39
Cross-link1171Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.39

Natural variations

Natural variant1051V → L in a renal chromophobe sample; somatic mutation. Ref.57
VAR_041424
Natural variant1381R → Q in IGF1RES; has decreased IGF1R function. Ref.55
VAR_034891
Natural variant1451K → N in IGF1RES; has decreased IGF1R function. Ref.55
VAR_034892
Natural variant3881V → M. Ref.4
Corresponds to variant rs45445894 [ dbSNP | Ensembl ].
VAR_018855
Natural variant4371R → H. Ref.57
Corresponds to variant rs34516635 [ dbSNP | Ensembl ].
VAR_034893
Natural variant5111R → Q.
Corresponds to variant rs33958176 [ dbSNP | Ensembl ].
VAR_034894
Natural variant5951R → H. Ref.57
Corresponds to variant rs56248469 [ dbSNP | Ensembl ].
VAR_041425
Natural variant6051R → H. Ref.4
Corresponds to variant rs45553041 [ dbSNP | Ensembl ].
VAR_018856
Natural variant7391R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. Ref.56
VAR_034895
Natural variant8081H → R.
Corresponds to variant rs34061581 [ dbSNP | Ensembl ].
VAR_034896
Natural variant8281A → T.
Corresponds to variant rs35224135 [ dbSNP | Ensembl ].
VAR_034897
Natural variant8571N → S. Ref.57
Corresponds to variant rs45611935 [ dbSNP | Ensembl ].
VAR_041426
Natural variant13381A → T. Ref.57
Corresponds to variant rs34102392 [ dbSNP | Ensembl ].
VAR_041427
Natural variant13471A → V in a lung squamous cell carcinoma sample; somatic mutation. Ref.57
VAR_041428

Experimental info

Mutagenesis9801Y → F: Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1, nor with GRB10. Ref.13 Ref.20
Mutagenesis10331K → A: Kinase inactive. Abolishes tyrosine phosphorylation and abolishes interaction with IRS1, SHC1 and PIK3R1. Ref.13
Mutagenesis12801Y → F: No effect on GRB10-binding. Ref.20
Mutagenesis12811Y → F: No effect on GRB10-binding. Ref.20
Mutagenesis13461Y → F: Loss of GRB10-binding. Ref.20
Sequence conflict928 – 9292TG → R in BAG11657. Ref.3

Secondary structure

........................................................................................................................................................ 1367
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08069 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: AE8A735F87F745C8

FASTA1,367154,793
        10         20         30         40         50         60 
MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGYLH 

        70         80         90        100        110        120 
ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF 

       130        140        150        160        170        180 
EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTVDWSLI LDAVSNNYIV GNKPPKECGD 

       190        200        210        220        230        240 
LCPGTMEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSTCG KRACTENNEC CHPECLGSCS 

       250        260        270        280        290        300 
APDNDTACVA CRHYYYAGVC VPACPPNTYR FEGWRCVDRD FCANILSAES SDSEGFVIHD 

       310        320        330        340        350        360 
GECMQECPSG FIRNGSQSMY CIPCEGPCPK VCEEEKKTKT IDSVTSAQML QGCTIFKGNL 

       370        380        390        400        410        420 
LINIRRGNNI ASELENFMGL IEVVTGYVKI RHSHALVSLS FLKNLRLILG EEQLEGNYSF 

       430        440        450        460        470        480 
YVLDNQNLQQ LWDWDHRNLT IKAGKMYFAF NPKLCVSEIY RMEEVTGTKG RQSKGDINTR 

       490        500        510        520        530        540 
NNGERASCES DVLHFTSTTT SKNRIIITWH RYRPPDYRDL ISFTVYYKEA PFKNVTEYDG 

       550        560        570        580        590        600 
QDACGSNSWN MVDVDLPPNK DVEPGILLHG LKPWTQYAVY VKAVTLTMVE NDHIRGAKSE 

       610        620        630        640        650        660 
ILYIRTNASV PSIPLDVLSA SNSSSQLIVK WNPPSLPNGN LSYYIVRWQR QPQDGYLYRH 

       670        680        690        700        710        720 
NYCSKDKIPI RKYADGTIDI EEVTENPKTE VCGGEKGPCC ACPKTEAEKQ AEKEEAEYRK 

       730        740        750        760        770        780 
VFENFLHNSI FVPRPERKRR DVMQVANTTM SSRSRNTTAA DTYNITDPEE LETEYPFFES 

       790        800        810        820        830        840 
RVDNKERTVI SNLRPFTLYR IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW 

       850        860        870        880        890        900 
EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN 

       910        920        930        940        950        960 
YTARIQATSL SGNGSWTDPV FFYVQAKTGY ENFIHLIIAL PVAVLLIVGG LVIMLYVFHR 

       970        980        990       1000       1010       1020 
KRNNSRLGNG VLYASVNPEY FSAADVYVPD EWEVAREKIT MSRELGQGSF GMVYEGVAKG 

      1030       1040       1050       1060       1070       1080 
VVKDEPETRV AIKTVNEAAS MRERIEFLNE ASVMKEFNCH HVVRLLGVVS QGQPTLVIME 

      1090       1100       1110       1120       1130       1140 
LMTRGDLKSY LRSLRPEMEN NPVLAPPSLS KMIQMAGEIA DGMAYLNANK FVHRDLAARN 

      1150       1160       1170       1180       1190       1200 
CMVAEDFTVK IGDFGMTRDI YETDYYRKGG KGLLPVRWMS PESLKDGVFT TYSDVWSFGV 

      1210       1220       1230       1240       1250       1260 
VLWEIATLAE QPYQGLSNEQ VLRFVMEGGL LDKPDNCPDM LFELMRMCWQ YNPKMRPSFL 

      1270       1280       1290       1300       1310       1320 
EIISSIKEEM EPGFREVSFY YSEENKLPEP EELDLEPENM ESVPLDPSAS SSSLPLPDRH 

      1330       1340       1350       1360 
SGHKAENGPG PGVLVLRASF DERQPYAHMN GGRKNERALP LPQSSTC 

« Hide

References

« Hide 'large scale' references
[1]"Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity."
Ullrich A., Gray A., Tam A.W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Bon T.L., Kathuria S., Chen E., Jacobs S., Francke U., Ramachandran J., Fujita-Yamaguchi Y.
EMBO J. 5:2503-2512(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-56; 446-453; 503-524; 561-579; 668-672 AND 721-729.
Tissue: Placenta.
[2]"Insulin-like growth factor I receptor gene structure."
Abbot A.M., Bueno R., Pedrini M.T., Murray J.M., Smith R.J.
J. Biol. Chem. 267:10759-10763(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Nagase T., Kikuno R.F., Yamakawa H., Ohara O.
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal brain.
[4]NIEHS SNPs program
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-388 AND HIS-605.
[5]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Analysis of the human type I insulin-like growth factor receptor promoter region."
Cooke D.W., Bankert L.A., Roberts C.T. Jr., Leroith D., Casella S.J.
Biochem. Biophys. Res. Commun. 177:1113-1120(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
[8]"Characterization of human placental insulin-like growth factor-I/insulin hybrid receptors by protein microsequencing and purification."
Kasuya J., Paz I.B., Maddux B.A., Goldfine I.D., Hefta S.A., Fujita-Yamaguchi Y.
Biochemistry 32:13531-13536(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 31-45 AND 741-750, FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
Tissue: Placenta.
[9]"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes."
Lee S.-T., Strunk K.M., Spritz R.A.
Oncogene 8:3403-3410(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1137-1193, TISSUE SPECIFICITY.
Tissue: Melanocyte.
[10]"Interaction of the alpha beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation."
Tollefsen S.E., Stoszek R.M., Thompson K.
Biochemistry 30:48-54(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, AUTOPHOSPHORYLATION.
[11]"Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity."
Soos M.A., Field C.E., Siddle K.
Biochem. J. 290:419-426(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
[12]"Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3)."
Kato H., Faria T.N., Stannard B., Roberts C.T. Jr., LeRoith D.
J. Biol. Chem. 268:2655-2661(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION.
[13]"Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor."
Craparo A., O'Neill T.J., Gustafson T.A.
J. Biol. Chem. 270:15639-15643(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IRS1; SHC1 AND PIK3R1, MUTAGENESIS OF TYR-980 AND LYS-1033, PHOSPHORYLATION AT TYR-980.
[14]"Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting."
Bailyes E.M., Nave B.T., Soos M.A., Orr S.R., Hayward A.C., Siddle K.
Biochem. J. 327:209-215(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FORMATION OF A HYBRID RECEPTOR WITH INSR, TISSUE SPECIFICITY.
[15]"14-3-3 proteins interact with the insulin-like growth factor receptor but not the insulin receptor."
Furlanetto R.W., Dey B.R., Lopaczynski W., Nissley S.P.
Biochem. J. 327:765-771(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH 14-3-3 PROTEINS.
[16]"Distribution of insulin/insulin-like growth factor-I hybrid receptors in human tissues."
Federici M., Porzio O., Zucaro L., Fusco A., Borboni P., Lauro D., Sesti G.
Mol. Cell. Endocrinol. 129:121-126(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FORMATION OF A HYBRID RECEPTOR WITH INSR, TISSUE SPECIFICITY.
[17]"Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor."
Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.
J. Biol. Chem. 273:24095-24101(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SOCS1 AND SOCS2.
[18]"beta-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor."
Lin F.-T., Daaka Y., Lefkowitz R.J.
J. Biol. Chem. 273:31640-31643(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[19]"The IGF-I receptor in cancer research."
Baserga R.
Exp. Cell Res. 253:1-6(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CANCER.
[20]"Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis."
Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., Swamy O.R., Leone M.E., Riedel H.
Mol. Cell. Biol. 19:6217-6228(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB10, MUTAGENESIS OF TYR-980; TYR-1280; TYR-1281 AND TYR-1346.
[21]"Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor."
Dey B.R., Furlanetto R.W., Nissley P.
Biochem. Biophys. Res. Commun. 278:38-43(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SOCS3.
[22]"Autophosphorylation of the insulin-like growth factor I receptor cytoplasmic domain."
Lopaczynski W., Terry C., Nissley P.
Biochem. Biophys. Res. Commun. 279:955-960(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION.
[23]"Mechanism of STAT3 activation by insulin-like growth factor I receptor."
Zong C.S., Chan J., Levy D.E., Horvath C., Sadowski H.B., Wang L.H.
J. Biol. Chem. 275:15099-15105(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF STAT3.
[24]"Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease."
Hellawell G.O., Turner G.D., Davies D.R., Poulsom R., Brewster S.F., Macaulay V.M.
Cancer Res. 62:2942-2950(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[25]"Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved."
Pandini G., Frasca F., Mineo R., Sciacca L., Vigneri R., Belfiore A.
J. Biol. Chem. 277:39684-39695(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
[26]"RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix."
Hermanto U., Zong C.S., Li W., Wang L.H.
Mol. Cell. Biol. 22:2345-2365(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNB2L1.
[27]"Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1)."
Galvan V., Logvinova A., Sperandio S., Ichijo H., Bredesen D.E.
J. Biol. Chem. 278:13325-13332(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K5.
[28]"Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor."
Girnita L., Girnita A., Larsson O.
Proc. Natl. Acad. Sci. U.S.A. 100:8247-8252(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY MDM2, INTERACTION WITH MDM2.
[29]"Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth."
Girnita A., Girnita L., del Prete F., Bartolazzi A., Larsson O., Axelson M.
Cancer Res. 64:236-242(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[30]"{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase."
Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., Lefkowitz R.J., Larsson O.
J. Biol. Chem. 280:24412-24419(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[31]"JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3."
Yadav A., Kalita A., Dhillon S., Banerjee K.
J. Biol. Chem. 280:31830-31840(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STAT3.
[32]"Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant."
Slaaby R., Schaeffer L., Lautrup-Larsen I., Andersen A.S., Shaw A.C., Mathiasen I.S., Brandt J.
J. Biol. Chem. 281:25869-25874(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
[33]"The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis."
McElroy B., Powell J.C., McCarthy J.V.
Biochem. Biophys. Res. Commun. 358:1136-1141(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[34]"The insulin-like growth factor 1 receptor in cancer: old focus, new future."
Hartog H., Wesseling J., Boezen H.M., van der Graaf W.T.
Eur. J. Cancer 43:1895-1904(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON IGF1R IN CANCER.
[35]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[36]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[37]"Development and validation of a method for profiling post-translational modification activities using protein microarrays."
Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., Spruck C.
PLoS ONE 5:E11332-E11332(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION.
[38]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[39]"Polyubiquitination of insulin-like growth factor I receptor (IGF-IR) activation loop promotes antibody-induced receptor internalization and down-regulation."
Mao Y., Shang Y., Pham V.C., Ernst J.A., Lill J.R., Scales S.J., Zha J.
J. Biol. Chem. 286:41852-41861(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-1168 AND LYS-1171.
[40]"Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor."
Garrett T.P., McKern N.M., Lou M., Frenkel M.J., Bentley J.D., Lovrecz G.O., Elleman T.C., Cosgrove L.J., Ward C.W.
Nature 394:395-399(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 31-492, DISULFIDE BONDS, GLYCOSYLATION AT ASN-51; ASN-135; ASN-244 AND ASN-314.
[41]"Structure and autoregulation of the insulin-like growth factor 1 receptor kinase."
Favelyukis S., Till J.H., Hubbard S.R., Miller W.T.
Nat. Struct. Biol. 8:1058-1063(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 988-1286 IN COMPLEX WITH AMP-PCP AND PEPTIDE SUBSTRATE, CATALYTIC ACTIVITY, ACTIVE SITE, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
[42]"Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation."
Pautsch A., Zoephel A., Ahorn H., Spevak W., Hauptmann R., Nar H.
Structure 9:955-965(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 981-1286 IN COMPLEX WITH ANP, AUTOPHOSPHORYLATION, ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY.
[43]"Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity."
Munshi S., Kornienko M., Hall D.L., Reid J.C., Waxman L., Stirdivant S.M., Darke P.L., Kuo L.C.
J. Biol. Chem. 277:38797-38802(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 974-1294.
[44]"Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 A resolution."
Munshi S., Hall D.L., Kornienko M., Darke P.L., Kuo L.C.
Acta Crystallogr. D 59:1725-1730(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 974-1294.
[45]"Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)."
Velaparthi U., Wittman M., Liu P., Stoffan K., Zimmermann K., Sang X., Carboni J., Li A., Attar R., Gottardis M., Greer A., Chang C.Y., Jacobsen B.L., Sack J.S., Sun Y., Langley D.R., Balasubramanian B., Vyas D.
Bioorg. Med. Chem. Lett. 17:2317-2321(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 982-1286 IN COMPLEX WITH BENZIMIDAZOLE PYRIDINONE INHIBITOR, CATALYTIC ACTIVITY, ENZYME REGULATION.
[46]"Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment."
Mayer S.C., Banker A.L., Boschelli F., Di L., Johnson M., Kenny C.H., Krishnamurthy G., Kutterer K., Moy F., Petusky S., Ravi M., Tkach D., Tsou H.R., Xu W.
Bioorg. Med. Chem. Lett. 18:3641-3645(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 981-1286, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
[47]"Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor."
Wu J., Li W., Craddock B.P., Foreman K.W., Mulvihill M.J., Ji Q.S., Miller W.T., Hubbard S.R.
EMBO J. 27:1985-1994(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 986-1286 IN COMPLEX WITH INHIBITOR PQIP, SUBUNIT, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, ACTIVE SITE, ENZYME REGULATION.
[48]"Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment."
Miller L.M., Mayer S.C., Berger D.M., Boschelli D.H., Boschelli F., Di L., Du X., Dutia M., Floyd M.B., Johnson M., Kenny C.H., Krishnamurthy G., Moy F., Petusky S., Tkach D., Torres N., Wu B., Xu W.
Bioorg. Med. Chem. Lett. 19:62-66(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 981-1286 IN COMPLEX WITH 3-CYANOQUINOLINE INHIBITOR, CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
[49]"Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development."
Wittman M.D., Carboni J.M., Yang Z., Lee F.Y., Antman M., Attar R., Balimane P., Chang C., Chen C., Discenza L., Frennesson D., Gottardis M.M., Greer A., Hurlburt W., Johnson W., Langley D.R., Li A., Li J. expand/collapse author list , Liu P., Mastalerz H., Mathur A., Menard K., Patel K., Sack J., Sang X., Saulnier M., Smith D., Stefanski K., Trainor G., Velaparthi U., Zhang G., Zimmermann K., Vyas D.M.
J. Med. Chem. 52:7360-7363(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 982-1286 IN COMPLEX WITH BMS-754807, CATALYTIC ACTIVITY, ENZYME REGULATION.
[50]"Allosteric IGF-1R Inhibitors."
Heinrich T., Graedler U., Boettcher H., Blaukat A., Shutes A.
ACS Med. Chem. Lett. 1:199-203(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 983-1286 IN COMPLEX WITH MSC1609119A-1, CATALYTIC ACTIVITY, ENZYME REGULATION.
[51]"Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase."
Sampognaro A.J., Wittman M.D., Carboni J.M., Chang C., Greer A.F., Hurlburt W.W., Sack J.S., Vyas D.M.
Bioorg. Med. Chem. Lett. 20:5027-5030(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 982-1286 IN COMPLEXES WITH INHIBITORS, CATALYTIC ACTIVITY, ENZYME REGULATION.
[52]"Design of potent IGF1-R inhibitors related to bis-azaindoles."
Nemecek C., Metz W.A., Wentzler S., Ding F.X., Venot C., Souaille C., Dagallier A., Maignan S., Guilloteau J.P., Bernard F., Henry A., Grapinet S., Lesuisse D.
Chem. Biol. Drug Des. 76:100-106(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 951-1286 IN COMPLEX WITH BIS-AZAINDOLE INHIBITOR, AUTOPHOSPHORYLATION, ENZYME REGULATION.
[53]"Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors."
Lesuisse D., Mauger J., Nemecek C., Maignan S., Boiziau J., Harlow G., Hittinger A., Ruf S., Strobel H., Nair A., Ritter K., Malleron J.L., Dagallier A., El-Ahmad Y., Guilloteau J.P., Guizani H., Bouchard H., Venot C.
Bioorg. Med. Chem. Lett. 21:2224-2228(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 982-1286 IN COMPLEX WITH HYDANTOIN DERIVATIVE, CATALYTIC ACTIVITY, ENZYME REGULATION.
[54]"Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors."
Buchanan J.L., Newcomb J.R., Carney D.P., Chaffee S.C., Chai L., Cupples R., Epstein L.F., Gallant P., Gu Y., Harmange J.C., Hodge K., Houk B.E., Huang X., Jona J., Joseph S., Jun H.T., Kumar R., Li C. expand/collapse author list , Lu J., Menges T., Morrison M.J., Novak P.M., van der Plas S., Radinsky R., Rose P.E., Sawant S., Sun J.R., Surapaneni S., Turci S.M., Xu K., Yanez E., Zhao H., Zhu X.
Bioorg. Med. Chem. Lett. 21:2394-2399(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 988-1286 IN COMPLEX WITH 2,4-BIS-ARYLAMINO-1,3-PYRIMIDINE INHIBITOR, CATALYTIC ACTIVITY, ENZYME REGULATION.
[55]"IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation."
The intrauterine growth retardation (IUGR) study group
Abuzzahab M.J., Schneider A., Goddard A., Grigorescu F., Lautier C., Keller E., Kiess W., Klammt J., Kratzsch J., Osgood D., Pfaeffle R., Raile K., Seidel B., Smith R.J., Chernausek S.D.
N. Engl. J. Med. 349:2211-2222(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IGF1RES GLN-138 AND ASN-145, CHARACTERIZATION OF VARIANTS IGF1RES GLN-138 AND ASN-145.
[56]"Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation."
Kawashima Y., Kanzaki S., Yang F., Kinoshita T., Hanaki K., Nagaishi J., Ohtsuka Y., Hisatome I., Ninomoya H., Nanba E., Fukushima T., Takahashi S.
J. Clin. Endocrinol. Metab. 90:4679-4687(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IGF1RES GLN-739, CHARACTERIZATION OF VARIANT IGF1RES GLN-739.
[57]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-105; HIS-437; HIS-595; SER-857; THR-1338 AND VAL-1347.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10378.1.
PIRIGHUR1. A25690.
RefSeqNP_000866.1. NM_000875.4.
NP_001278787.1. NM_001291858.1.
UniGeneHs.643120.
Hs.714012.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP08069.
SMRP08069. Positions 30-924, 957-1317.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109701. 50 interactions.
DIPDIP-476N.
IntActP08069. 39 interactions.
MINTMINT-85902.
STRING9606.ENSP00000268035.

Chemistry

BindingDBP08069.
ChEMBLCHEMBL1957.
DrugBankDB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.
DB01277. Mecasermin.
GuidetoPHARMACOLOGY1801.

PTM databases

PhosphoSiteP08069.

Polymorphism databases

DMDM124240.

Proteomic databases

MaxQBP08069.
PaxDbP08069.
PeptideAtlasP08069.
PRIDEP08069.

Protocols and materials databases

DNASU3480.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268035; ENSP00000268035; ENSG00000140443.
GeneID3480.
KEGGhsa:3480.
UCSCuc002bul.3. human.

Organism-specific databases

CTD3480.
GeneCardsGC15P099192.
HGNCHGNC:5465. IGF1R.
HPACAB010268.
MIM147370. gene.
270450. phenotype.
neXtProtNX_P08069.
Orphanet73273. Growth delay due to insulin-like growth factor I resistance.
PharmGKBPA29698.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000038045.
HOVERGENHBG006134.
InParanoidP08069.
KOK05087.
OMANRCQKMC.
OrthoDBEOG73RB9N.
PhylomeDBP08069.
TreeFamTF351636.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkP08069.

Gene expression databases

ArrayExpressP08069.
BgeeP08069.
CleanExHS_IGF1R.
GenevestigatorP08069.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProIPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
PfamPF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFPIRSF000620. Insulin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS50853. 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]
ProtoNetSearch...

Other

ChiTaRSIGF1R. human.
EvolutionaryTraceP08069.
GeneWikiInsulin-like_growth_factor_1_receptor.
GenomeRNAi3480.
NextBio13682.
PROP08069.
SOURCESearch...

Entry information

Entry nameIGF1R_HUMAN
AccessionPrimary (citable) accession number: P08069
Secondary accession number(s): B1B5Y2, Q14CV2, Q9UCC0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: July 9, 2014
This is version 173 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries