Reviewed, UniProtKB/Swiss-Prot P08069 (IGF1R_HUMAN)

Names and origin

Protein names

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:
    1- Recommended name:
            Insulin-like growth factor 1 receptor alpha chain
    2- Recommended name:
            Insulin-like growth factor 1 receptor beta chain

Gene names

Name:

IGF1R

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1367 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This receptor binds insulin-like growth factor 1 (IGF1) with a high affinity and IGF2 with a lower affinity. It has a tyrosine-protein kinase activity, which is necessary for the activation of the IGF1-stimulated downstream signaling cascade. When present in a hybrid receptor with INSR, binds IGF1. Ref.18 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, Ref.20 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. Ref.7 Ref.10 Ref.11 Ref.12 Ref.18 Ref.20
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.12
Cofactor	Manganese.
Enzyme regulation	Autophosphorylation activates the kinase activity. Ref.9
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. Ref.10 Ref.13 Ref.16 Ref.19
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibrobasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Ref.8 Ref.14 Ref.15
Post-translational modification	The cytoplasmic domain of the beta subunit is autophosphorylated on tyrosine residues in response to insulin-like growth factor I (IGF I). Ref.10 Ref.12 Ref.17 Ref.21 Ref.22 Ref.23 Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding.
Involvement in disease	Defects in IGF1R may be a cause in some cases of resistance to insulin-like growth factor 1 (IGF1 resistance) [MIM:270450]. IGF1 resistance is a gowth deficiency disorder characterized by intrauterine growth retardation and poor postnatal growth accompanied with increased plasma IGF1.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. Contains 3 fibronectin type-III domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc immune response Inferred from mutant phenotype. Source: UniProtKB insulin receptor signaling pathway Traceable author statement. Source: ProtInc insulin-like growth factor receptor signaling pathway Ref.12 Inferred from direct assay. Source: UniProtKB phosphoinositide 3-kinase cascade Ref.13 Inferred by curator. Source: UniProtKB phosphoinositide-mediated signaling Inferred from direct assay. Source: UniProtKB positive regulation of DNA replication Ref.18 Inferred from mutant phenotype. Source: UniProtKB positive regulation of cell migration Ref.18 Inferred from mutant phenotype. Source: UniProtKB positive regulation of cell proliferation Traceable author statement. Source: ProtInc protein amino acid autophosphorylation Ref.10 Ref.12 Ref.17 Inferred from direct assay. Source: UniProtKB protein tetramerization Ref.10 Inferred from direct assay. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.12 Inferred by curator. Source: UniProtKB microsome Ref.11 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Inferred from physical interaction. Source: IntAct insulin binding Ref.11 Inferred from physical interaction. Source: UniProtKB insulin receptor binding Ref.11 Inferred from direct assay. Source: UniProtKB insulin receptor substrate binding Ref.13 Inferred from physical interaction. Source: UniProtKB insulin-like growth factor I binding Ref.11 Inferred from physical interaction. Source: UniProtKB insulin-like growth factor receptor activity Ref.12 Inferred from direct assay. Source: UniProtKB manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoinositide 3-kinase binding Ref.13 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-475981,EBI-475981
SLC23A3	Q6PIS1	1	EBI-475981,EBI-2362199
YWHAG	P61981	1	EBI-475981,EBI-359832

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Ref.7 Ref.1

Chain

31 – 736

706

Insulin-like growth factor 1 receptor alpha chain

PRO_0000016681

Chain

741 – 1367

627

Insulin-like growth factor 1 receptor beta chain

PRO_0000016682

Regions

Topological domain

741 – 935

195

Extracellular Potential

Transmembrane

936 – 959

24

Potential

Topological domain

960 – 1367

408

Cytoplasmic Potential

Domain

488 – 606

119

Fibronectin type-III 1

Domain

611 – 689

79

Fibronectin type-III 2

Domain

831 – 926

96

Fibronectin type-III 3

Domain

999 – 1274

276

Protein kinase

Nucleotide binding

1005 – 1013

9

ATP By similarity

Motif

977 – 980

4

IRS1- and SHC1-binding

Sites

Active site

1135

1

Proton acceptor By similarity

Binding site

1033

1

ATP

Amino acid modifications

Modified residue

980

1

Phosphotyrosine; by autocatalysis

Modified residue

1161

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

1165

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

1166

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

1339

1

Phosphoserine Ref.22 Ref.23

Modified residue

1365

1

Phosphoserine

Modified residue

1366

1

Phosphothreonine Ref.22

Glycosylation

51

1

N-linked (GlcNAc...) Potential

Glycosylation

102

1

N-linked (GlcNAc...) Potential

Glycosylation

135

1

N-linked (GlcNAc...) Potential

Glycosylation

244

1

N-linked (GlcNAc...) Potential

Glycosylation

314

1

N-linked (GlcNAc...) Potential

Glycosylation

417

1

N-linked (GlcNAc...) Potential

Glycosylation

438

1

N-linked (GlcNAc...) Potential

Glycosylation

534

1

N-linked (GlcNAc...) Potential

Glycosylation

607

1

N-linked (GlcNAc...) Potential

Glycosylation

622

1

N-linked (GlcNAc...) Potential

Glycosylation

640

1

N-linked (GlcNAc...) Potential

Glycosylation

747

1

N-linked (GlcNAc...) Potential

Glycosylation

756

1

N-linked (GlcNAc...) Potential

Glycosylation

764

1

N-linked (GlcNAc...) Potential

Glycosylation

900

1

N-linked (GlcNAc...) Potential

Glycosylation

913

1

N-linked (GlcNAc...) Potential

Disulfide bond

215 ↔ 224

By similarity

Disulfide bond

219 ↔ 230

By similarity

Disulfide bond

231 ↔ 239

By similarity

Disulfide bond

235 ↔ 248

By similarity

Disulfide bond

251 ↔ 260

By similarity

Disulfide bond

264 ↔ 276

By similarity

Disulfide bond

282 ↔ 303

By similarity

Disulfide bond

307 ↔ 321

By similarity

Disulfide bond

324 ↔ 328

By similarity

Natural variations

Natural variant

105

1

V → L in a renal chromophobe sample; somatic mutation. Ref.27

VAR_041424

Natural variant

138

1

R → Q in IGF1 resistance; has decreased IGF1R function. Ref.25

VAR_034891

Natural variant

145

1

K → N in IGF1 resistance; has decreased IGF1R function. Ref.25

VAR_034892

Natural variant

388

1

V → M: dbSNP rs45445894. Ref.4

VAR_018855

Natural variant

437

1

R → H: dbSNP rs34516635. Ref.27

VAR_034893

Natural variant

511

1

R → Q: dbSNP rs33958176.

VAR_034894

Natural variant

595

1

R → H: dbSNP rs56248469. Ref.27

VAR_041425

Natural variant

605

1

R → H: dbSNP rs45553041. Ref.4

VAR_018856

Natural variant

739

1

R → Q in IGF1 resistance; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. Ref.26

VAR_034895

Natural variant

808

1

H → R: dbSNP rs34061581.

VAR_034896

Natural variant

828

1

A → T: dbSNP rs35224135.

VAR_034897

Natural variant

857

1

N → S: dbSNP rs45611935. Ref.27

VAR_041426

Natural variant

1338

1

A → T: dbSNP rs34102392. Ref.27

VAR_041427

Natural variant

1347

1

A → V in a lung squamous cell carcinoma sample; somatic mutation. Ref.27

VAR_041428

Experimental info

Mutagenesis

980

1

Y → F: Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1. Ref.13

Mutagenesis

1033

1

K → A: Kinase inactive. Abolishes tyrosine phosphorylation and abolishes interaction with IRS1, SHC1 and PIK3R1. Ref.13

Sequence conflict

928 – 929

2

TG → R in BAG11657. Ref.3

Secondary structure

1

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1367

Helix Strand Turn

Details...

Beta strand

37 – 41

5

Helix

43 – 49

7

Beta strand

53 – 57

5

Beta strand

59 – 65

7

Beta strand

68 – 70

3

Beta strand

80 – 83

4

Beta strand

85 – 92

8

Helix

96 – 98

3

Beta strand

115 – 121

7

Beta strand

138 – 144

7

Helix

157 – 160

4

Helix

164 – 166

3

Beta strand

168 – 171

4

Helix

175 – 178

4

Turn

183 – 188

6

Beta strand

194 – 199

6

Beta strand

201 – 203

3

Beta strand

205 – 209

5

Helix

217 – 219

3

Beta strand

235 – 241

7

Beta strand

247 – 255

9

Beta strand

257 – 263

7

Beta strand

269 – 271

3

Turn

272 – 274

3

Beta strand

275 – 277

3

Helix

279 – 283

5

Beta strand

297 – 299

3

Beta strand

302 – 306

5

Beta strand

311 – 315

5

Beta strand

321 – 323

3

Beta strand

325 – 327

3

Beta strand

331 – 341

11

Helix

345 – 347

3

Turn

349 – 352

4

Beta strand

354 – 362

9

Helix

375 – 378

4

Beta strand

383 – 386

4

Beta strand

388 – 392

5

Turn

415 – 417

3

Beta strand

418 – 423

6

Turn

434 – 436

3

Beta strand

440 – 443

4

Beta strand

445 – 451

7

Helix

456 – 466

11

Beta strand

474 – 477

4

Turn

479 – 481

3

Beta strand

980 – 982

3

Beta strand

998 – 1007

10

Beta strand

1009 – 1022

14

Beta strand

1025 – 1034

10

Helix

1041 – 1051

11

Helix

1052 – 1056

5

Beta strand

1065 – 1069

5

Beta strand

1071 – 1074

4

Beta strand

1076 – 1080

5

Helix

1087 – 1094

8

Helix

1109 – 1128

20

Helix

1138 – 1140

3

Beta strand

1141 – 1143

3

Beta strand

1149 – 1151

3

Helix

1176 – 1178

3

Helix

1181 – 1186

6

Helix

1191 – 1206

16

Turn

1212 – 1215

4

Helix

1218 – 1226

9

Helix

1239 – 1248

10

Helix

1253 – 1255

3

Helix

1259 – 1264

6

Helix

1267 – 1269

3

Helix

1274 – 1277

4

Sequences

	Sequence		Length	Mass (Da)
	P08069-1 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: AE8A735F87F745C8	FASTA	1,367	154,793
	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

References

	« Hide 'large scale' referencesShow '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: 2877871] [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: 1316909] [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]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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: 1711844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
[7]	"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: 8257688] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-45 AND 741-750, FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR. Tissue: Placenta.
[8]	"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: 8247543] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1137-1193, TISSUE SPECIFICITY. Tissue: Melanocyte.
[9]	"Substructural analysis of the insulin receptor by microsequence analyses of limited tryptic fragments isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence or presence of dithiothreitol." Xu Q.-Y., Paxton R.J., Fujita-Yamaguchi Y. J. Biol. Chem. 265:18673-18681(1990) [PubMed: 2211730] [Abstract] Cited for: ENZYME REGULATION, BINDING OF MANGANESE. Tissue: Placenta.
[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: 1846292] [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: 8452530] [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: 7679099] [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: 7541045] [Abstract] Cited for: INTERACTION WITH IRS1; SHC1 AND PIK3R1, MUTAGENESIS OF TYR-980 AND LYS-1033.
[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: 9355755] [Abstract] Cited for: FORMATION OF A HYBRID RECEPTOR WITH INSR, TISSUE SPECIFICITY.
[15]	"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: 9202395] [Abstract] Cited for: FORMATION OF A HYBRID RECEPTOR WITH INSR, TISSUE SPECIFICITY.
[16]	"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: 9822622] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[17]	"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: 11162456] [Abstract] Cited for: AUTOPHOSPHORYLATION.
[18]	"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: 12138094] [Abstract] Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
[19]	"{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: 15878855] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[20]	"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: 16831875] [Abstract] Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
[21]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1161; TYR-1165 AND TYR-1166, MASS SPECTROMETRY. Tissue: Lung.
[22]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1161; TYR-1165; SER-1339 AND THR-1366, MASS SPECTROMETRY.
[23]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1339, MASS SPECTROMETRY.
[24]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1165; SER-1339; SER-1365 AND THR-1366, MASS SPECTROMETRY.
[25]	"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: 14657428] [Abstract] Cited for: VARIANTS IGF1 RESISTANCE GLN-138 AND ASN-145, CHARACTERIZATION OF VARIANTS IGF1 RESISTANCE GLN-138 AND ASN-145.
[26]	"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: 15928254] [Abstract] Cited for: VARIANT IGF1 RESISTANCE GLN-739, CHARACTERIZATION OF VARIANT IGF1 RESISTANCE GLN-739.
[27]	"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. , 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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-105; HIS-437; HIS-595; SER-857; THR-1338 AND VAL-1347.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Wikipedia

IGF-1 receptor entry

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.
BC113610 mRNA. Translation: AAI13611.1.
BC113612 mRNA. Translation: AAI13613.1.
M69229 Genomic DNA. Translation: AAB59399.1.

IPI

IPI00027232.

PIR

IGHUR1. A25690.

RefSeq

NP_000866.1.

UniGene

Hs.643120
Hs.653608
Hs.714012

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IGR	X-ray	2.60	A	31-492	[»]
1JQH	X-ray	2.10	A/B/C	981-1286	[»]
1K3A	X-ray	2.10	A	988-1286	[»]
1M7N	X-ray	2.70	A/B	974-1294	[»]
1P4O	X-ray	1.50	A/B	974-1294	[»]
2OJ9	X-ray	2.00	A	982-1286	[»]
2ZM3	X-ray	2.50	A/B/C/D	981-1286	[»]
3D94	X-ray	2.30	A	986-1286	[»]
3F5P	X-ray	2.90	A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T	981-1286	[»]
3I81	X-ray	2.08	A	982-1286	[»]

SMR

P08069. Positions 29-926.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-476N.

IntAct

P08069. 12 interactions.

STRING

P08069.

PTM databases

PhosphoSite

P08069.

Proteomic databases

PeptideAtlas

P08069.

PRIDE

P08069.

Genome annotation databases

Ensembl

ENST00000268035; ENSP00000268035; ENSG00000140443; Homo sapiens. [Genome view]

GeneID

3480.

KEGG

hsa:3480.

UCSC

uc002bul.1. human.

Organism-specific databases

CTD

3480.

GeneCards

GC15P097010.

H-InvDB

HIX0038072.

HGNC

HGNC:5465. IGF1R.

HPA

CAB010268.

MIM

147370. gene.
270450. phenotype.

Orphanet

73273. Growth delay due to insulin-like growth factor I resistance.

PharmGKB

PA29698.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04495.

HOGENOM

HBG316019.

HOVERGEN

P08069.

InParanoid

P08069.

OMA

TTINNEY.

OrthoDB

EOG986BZ0.

PhylomeDB

P08069.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

igf1_pathway. IGF1 pathway.
avb3_integrin_pathway. Integrins in angiogenesis.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.

Gene expression databases

ArrayExpress

P08069.

Bgee

P08069.

CleanEx

HS_IGF1R.

Genevestigator

P08069.

GermOnline

ENSG00000140443. Homo sapiens.

Family and domain databases

InterPro

IPR000494. EGF_rcpt_L.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR020714. Tyr_kinase_insulin_GF_rcpt.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR002011. Tyr_prot_kinase_rcpt_2_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 1 hit.

PANTHER

PTHR23256:SF178. Tyr_kinase_insulin_GF_rcpt. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

PF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]

PIRSF

PIRSF000620. Insulin_receptor. 1 hit.

SMART

SM00060. FN3. 3 hits.
SM00261. FU. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS50853. FN3. 3 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]

ProtoNet

Search...

Other Resources

DrugBank

DB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.
DB01277. Mecasermin.

NextBio

13682.

SOURCE

Search...

Entry information

Entry name

IGF1R_HUMAN

Accession

Primary (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:	February 9, 2010
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.