P08069 (IGF1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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. Insulin-like growth factor 1 receptor alpha chain
2. Insulin-like growth factor 1 receptor beta chain

Gene names

Name:

IGF1R

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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 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.32 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.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.40 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.52 Ref.53
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.40 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53
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.46
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, 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. Dephosphorylated by PTPN1 By similarity. Ref.10 Ref.12 Ref.22 Ref.40 Ref.41 Ref.45 Ref.46 Ref.47 Ref.51 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.
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.54 Ref.55
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.
Sequence caution	The sequence BAG11657.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	axonogenesis Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara establishment of cell polarity Inferred from electronic annotation. Source: Compara exocrine pancreas development Inferred from electronic annotation. Source: Compara 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 male sex determination Inferred from electronic annotation. Source: Compara mammary gland development Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from direct assay Ref.27. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara phosphatidylinositol 3-kinase cascade Inferred by curator Ref.13. 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: Compara 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: Compara positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of steroid hormone biosynthetic process Inferred from electronic annotation. Source: Compara prostate gland epithelium morphogenesis Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay Ref.22Ref.10Ref.12. Source: UniProtKB protein heterooligomerization Inferred from electronic annotation. Source: Compara 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: Compara
Cellular_component	caveola Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred by curator Ref.12. Source: UniProtKB intracellular membrane-bounded organelle Inferred from direct assay Ref.11. Source: BHF-UCL neuron projection Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW insulin binding Inferred from physical interaction Ref.11. Source: BHF-UCL insulin receptor binding Inferred from direct assay 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-475981,EBI-475981
CAMP	P49913	3	EBI-475981,EBI-6378485
SHC1	P29353-2	2	EBI-475981,EBI-1000553

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Ref.1 Ref.8

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

Helical; 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

Modified residue

1161

1

Phosphotyrosine; by autocatalysis Ref.40 Ref.45 Ref.47

Modified residue

1165

1

Phosphotyrosine; by autocatalysis Ref.40 Ref.45 Ref.47

Modified residue

1166

1

Phosphotyrosine; by autocatalysis Ref.40 Ref.45 Ref.47

Modified residue

1339

1

Phosphoserine Ref.36

Glycosylation

51

1

N-linked (GlcNAc...) Ref.39

Glycosylation

102

1

N-linked (GlcNAc...) Potential

Glycosylation

135

1

N-linked (GlcNAc...) Ref.39

Glycosylation

244

1

N-linked (GlcNAc...) Ref.39

Glycosylation

314

1

N-linked (GlcNAc...) Ref.39

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

33 ↔ 52

Ref.39

Disulfide bond

150 ↔ 178

Ref.39

Disulfide bond

182 ↔ 205

Ref.39

Disulfide bond

192 ↔ 211

Ref.39

Disulfide bond

215 ↔ 224

Ref.39

Disulfide bond

219 ↔ 230

Ref.39

Disulfide bond

231 ↔ 239

Ref.39

Disulfide bond

235 ↔ 248

Ref.39

Disulfide bond

251 ↔ 260

Ref.39

Disulfide bond

264 ↔ 276

Ref.39

Disulfide bond

282 ↔ 303

Ref.39

Disulfide bond

307 ↔ 321

Ref.39

Disulfide bond

324 ↔ 328

Ref.39

Disulfide bond

332 ↔ 353

Ref.39

Disulfide bond

455 ↔ 488

Ref.39

Cross-link

1168

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.38

Cross-link

1171

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.38

Natural variations

Natural variant

105

1

V → L in a renal chromophobe sample; somatic mutation. Ref.56

VAR_041424

Natural variant

138

1

R → Q in IGF1RES; has decreased IGF1R function. Ref.54

VAR_034891

Natural variant

145

1

K → N in IGF1RES; has decreased IGF1R function. Ref.54

VAR_034892

Natural variant

388

1

V → M. Ref.49
Corresponds to variant rs45445894 [ dbSNP | Ensembl ].

VAR_018855

Natural variant

437

1

R → H. Ref.56
Corresponds to variant rs34516635 [ dbSNP | Ensembl ].

VAR_034893

Natural variant

511

1

R → Q.
Corresponds to variant rs33958176 [ dbSNP | Ensembl ].

VAR_034894

Natural variant

595

1

R → H. Ref.56
Corresponds to variant rs56248469 [ dbSNP | Ensembl ].

VAR_041425

Natural variant

605

1

R → H. Ref.49
Corresponds to variant rs45553041 [ dbSNP | Ensembl ].

VAR_018856

Natural variant

739

1

R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. Ref.55

VAR_034895

Natural variant

808

1

H → R.
Corresponds to variant rs34061581 [ dbSNP | Ensembl ].

VAR_034896

Natural variant

828

1

A → T.
Corresponds to variant rs35224135 [ dbSNP | Ensembl ].

VAR_034897

Natural variant

857

1

N → S. Ref.56
Corresponds to variant rs45611935 [ dbSNP | Ensembl ].

VAR_041426

Natural variant

1338

1

A → T. Ref.56
Corresponds to variant rs34102392 [ dbSNP | Ensembl ].

VAR_041427

Natural variant

1347

1

A → V in a lung squamous cell carcinoma sample; somatic mutation. Ref.56

VAR_041428

Experimental info

Mutagenesis

980

1

Y → F: Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1, nor with GRB10. Ref.13 Ref.20

Mutagenesis

1033

1

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

Mutagenesis

1280

1

Y → F: No effect on GRB10-binding. Ref.20

Mutagenesis

1281

1

Y → F: No effect on GRB10-binding. Ref.20

Mutagenesis

1346

1

Y → F: Loss of GRB10-binding. Ref.20

Sequence conflict

928 – 929

2

TG → R in BAG11657. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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

Helix

983 – 985

3

Turn

990 – 992

3

Helix

996 – 998

3

Beta strand

999 – 1007

9

Beta strand

1009 – 1022

14

Beta strand

1025 – 1034

10

Beta strand

1037 – 1039

3

Helix

1041 – 1053

13

Helix

1054 – 1056

3

Beta strand

1065 – 1069

5

Beta strand

1071 – 1074

4

Beta strand

1076 – 1080

5

Helix

1087 – 1100

14

Helix

1109 – 1128

20

Helix

1138 – 1140

3

Beta strand

1141 – 1143

3

Beta strand

1149 – 1151

3

Helix

1155 – 1157

3

Helix

1159 – 1164

6

Helix

1168 – 1170

3

Beta strand

1171 – 1174

4

Helix

1176 – 1178

3

Helix

1181 – 1186

6

Helix

1191 – 1207

17

Turn

1212 – 1215

4

Helix

1218 – 1226

9

Helix

1239 – 1248

10

Helix

1253 – 1255

3

Helix

1259 – 1266

8

Helix

1267 – 1269

3

Helix

1274 – 1277

4

Turn

1279 – 1281

3

Turn

1283 – 1285

3

Sequences

	Sequence		Length	Mass (Da)
	P08069 [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] [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. , 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.
[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 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.
[34]	"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.
[35]	"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] [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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1339, MASS SPECTROMETRY.
[37]	"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.
[38]	"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.
[39]	"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.
[40]	"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, MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
[41]	"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, MASS SPECTROMETRY.
[42]	"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.
[43]	"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.
[44]	"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.
[45]	"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.
[46]	"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.
[47]	"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.
[48]	"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. , 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.
[49]	"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.
[50]	"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.
[51]	"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.
[52]	"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.
[53]	"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. , 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.
[54]	"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.
[55]	"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.
[56]	"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] [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.

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.
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.

IPI

IPI00027232.

PIR

IGHUR1. A25690.

RefSeq

NP_000866.1. NM_000875.3.

UniGene

Hs.643120.
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	[»]
3LVP	X-ray	3.00	A/B/C/D	951-1286	[»]
3LW0	X-ray	1.79	A/B/C/D	983-1286	[»]
3NW5	X-ray	2.14	A	982-1286	[»]
3NW6	X-ray	2.20	A	982-1286	[»]
3NW7	X-ray	2.11	A	982-1286	[»]
3O23	X-ray	2.10	A	982-1286	[»]
3QQU	X-ray	2.90	A/B/C/D	988-1286	[»]

ProteinModelPortal

P08069.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-476N.

IntAct

P08069. 21 interactions.

MINT

MINT-85902.

STRING

9606.ENSP00000268035.

PTM databases

PhosphoSite

P08069.

Polymorphism databases

DMDM

124240.

Proteomic databases

PaxDb

P08069.

PeptideAtlas

P08069.

PRIDE

P08069.

Protocols and materials databases

DNASU

3480.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000268035; ENSP00000268035; ENSG00000140443.

GeneID

3480.

KEGG

hsa:3480.

UCSC

uc002bul.3. human.

Organism-specific databases

CTD

3480.

GeneCards

GC15P099192.

HGNC

HGNC:5465. IGF1R.

HPA

CAB010268.

MIM

147370. gene.
270450. phenotype.

neXtProt

NX_P08069.

Orphanet

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

PharmGKB

PA29698.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000038045.

HOVERGEN

HBG006134.

InParanoid

P08069.

KO

K05087.

OMA

RCQKMCP.

OrthoDB

EOG4Z62MR.

PhylomeDB

P08069.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

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

Reactome

REACT_111102. Signal Transduction.

SignaLink

P08069.

Gene expression databases

ArrayExpress

P08069.

Bgee

P08069.

CleanEx

HS_IGF1R.

Genevestigator

P08069.

GermOnline

ENSG00000140443. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 4 hits.
3.80.20.20. 2 hits.

InterPro

IPR000494. 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_cat_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]

Pfam

PF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]

PIRSF

PIRSF000620. Insulin_receptor. 1 hit.

PRINTS

PR00109. TYRKINASE.

SMART

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

SUPFAM

SSF49265. FN_III-like. 3 hits.
SSF57184. Grow_fac_recept. 1 hit.
SSF56112. Kinase_like. 1 hit.

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

BindingDB

P08069.

ChEMBL

CHEMBL1957.

ChiTaRS

IGF1R. human.

DrugBank

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

EvolutionaryTrace

P08069.

GenomeRNAi

3480.

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:	May 29, 2013
This is version 161 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.