P06213 (INSR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin receptor
Short name=IR
EC=2.7.10.1

Alternative name(s):
CD_antigen=CD220

Cleaved into the following 2 chains:

1. Insulin receptor subunit alpha
2. Insulin receptor subunit beta

Gene names

Name:

INSR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1382 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 the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. Ref.38 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.44 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.12 Ref.24 Ref.25 Ref.29 Ref.33 Ref.38 Ref.41 Ref.44
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Activated in response to insulin. Autophosphorylation activates the kinase activity. PTP1B dephosphorylates important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates. Ref.11 Ref.34 Ref.37 Ref.39
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 chains carry the kinase domain. Forms a hybrid receptor with IGF1R, 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 SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 By similarity. Interacts with ARRB2 By similarity. Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with GRB7 By similarity. Interacts with PDPK1. Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-999, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF. Ref.25 Ref.26 Ref.27 Ref.29 Ref.30 Ref.31 Ref.34 Ref.35 Ref.36 Ref.37 Ref.39 Ref.40 Ref.41
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas. Ref.15 Ref.28 Ref.32 Ref.33
Post-translational modification	After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane. Ref.2 Ref.23 Ref.51 Ref.53 Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-999 is required for IRS1-, SHC1-, and STAT5B-binding. Dephosphorylated by PTPRE on Tyr-999, Tyr-1185, Tyr-1189 and Tyr-1190 residues. Dephosphorylated by PTPRF. Ref.15 Ref.17 Ref.22 Ref.29 Ref.31 Ref.41 Ref.42 Ref.43 Ref.46 Ref.48 Ref.49 Ref.50 Ref.52
Involvement in disease	Defects in INSR are the cause of Rabson-Mendenhall syndrome (RMS) [MIM:262190]; also known as Mendenhall syndrome. RMS is a severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive. Ref.63 Ref.64 Ref.84 Ref.98 Ref.102 Ref.106 Defects in INSR are the cause of leprechaunism (LEPRCH) [MIM:246200]; also known as Donohue syndrome. Leprechaunism represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive. Ref.59 Ref.60 Ref.64 Ref.69 Ref.72 Ref.81 Ref.82 Ref.86 Ref.88 Ref.90 Ref.92 Ref.95 Ref.96 Ref.97 Ref.102 Ref.103 Ref.104 Defects in INSR may be associated with noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2. Ref.70 Ref.73 Ref.89 Defects in INSR are the cause of familial hyperinsulinemic hypoglycemia type 5 (HHF5) [MIM:609968]. Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Ref.105 Defects in INSR are the cause of insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]. This syndrome is characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor.
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
Biological process	Carbohydrate metabolism
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Acetylation Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor signaling pathway Inferred from direct assay. Source: BHF-UCL activation of MAPK activity Inferred from mutant phenotype. Source: BHF-UCL activation of protein kinase B activity Inferred from direct assay. Source: BHF-UCL carbohydrate metabolic process Inferred from electronic annotation. Source: UniProtKB-KW fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome glucose homeostasis Inferred from mutant phenotype. Source: BHF-UCL heart morphogenesis Inferred from mutant phenotype. Source: BHF-UCL peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: BHF-UCL positive regulation of DNA replication Inferred from mutant phenotype Ref.38. Source: BHF-UCL positive regulation of MAPKKK cascade Inferred from mutant phenotype. Source: BHF-UCL positive regulation of cell migration Inferred from mutant phenotype Ref.38. Source: BHF-UCL positive regulation of cell proliferation Inferred from direct assay. Source: BHF-UCL positive regulation of developmental growth Inferred from mutant phenotype. Source: BHF-UCL positive regulation of glucose import Inferred from direct assay. Source: BHF-UCL positive regulation of glycogen biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of glycolysis Inferred from mutant phenotype. Source: BHF-UCL positive regulation of mitosis Inferred from mutant phenotype. Source: BHF-UCL positive regulation of nitric oxide biosynthetic process Inferred from mutant phenotype. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from mutant phenotype. Source: BHF-UCL positive regulation of protein phosphorylation Inferred from direct assay. Source: BHF-UCL positive regulation of respiratory burst Inferred from direct assay. Source: BHF-UCL protein autophosphorylation Inferred from mutant phenotype Ref.27. Source: UniProtKB protein heterotetramerization Inferred from direct assay. Source: UniProtKB regulation of embryonic development Inferred from mutant phenotype. Source: BHF-UCL regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: BHF-UCL transformation of host cell by virus Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	caveola Inferred from direct assay. Source: BHF-UCL endosome membrane Traceable author statement. Source: Reactome insulin receptor complex Inferred from mutant phenotype. Source: BHF-UCL microsome Inferred from direct assay Ref.24. Source: BHF-UCL
Molecular function	ATP binding Inferred from direct assay. Source: BHF-UCL GTP binding Inferred from direct assay. Source: BHF-UCL PTB domain binding Inferred from physical interaction Ref.26. Source: UniProtKB SH2 domain binding Inferred from physical interaction Ref.25. Source: UniProtKB insulin binding Inferred from direct assay. Source: UniProtKB insulin receptor substrate binding Inferred from physical interaction Ref.27Ref.26. Source: UniProtKB insulin-activated receptor activity Inferred from direct assay. Source: UniProtKB insulin-like growth factor I binding Inferred from physical interaction Ref.24. Source: BHF-UCL insulin-like growth factor II binding Inferred from physical interaction Ref.38. Source: BHF-UCL insulin-like growth factor receptor binding Inferred from direct assay Ref.24. Source: BHF-UCL metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol 3-kinase binding Inferred from physical interaction Ref.27Ref.25. Source: UniProtKB receptor signaling protein tyrosine kinase activity Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P06213-1)

Also known as: HIR-B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P06213-2)

Also known as: HIR-A;

The sequence of this isoform differs from the canonical sequence as follows:
     745-756: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Ref.2 Ref.11 Ref.12

Chain

28 – 758

731

Insulin receptor subunit alpha

PRO_0000016687

Chain

763 – 1382

620

Insulin receptor subunit beta

PRO_0000016689

Regions

Topological domain

763 – 956

194

Extracellular Potential

Transmembrane

957 – 979

23

Helical; Potential

Topological domain

980 – 1382

403

Cytoplasmic Potential

Domain

622 – 695

74

Fibronectin type-III 1

Domain

757 – 842

86

Fibronectin type-III 2

Domain

850 – 946

97

Fibronectin type-III 3

Domain

1023 – 1298

276

Protein kinase

Nucleotide binding

1029 – 1037

9

ATP By similarity

Region

996 – 999

4

IRS1- and SHC1-binding

Region

1361 – 1364

4

PIK3R1-binding

Compositional bias

182 – 339

158

Cys-rich

Sites

Active site

1159

1

Proton acceptor By similarity

Binding site

1057

1

ATP

Site

996

1

Essential for IRS1-binding and important but not critical for SHC1-binding

Site

997

1

Essential for IRS1-binding and important but not critical for SHC1-binding

Site

999

1

Important for biological activity

Amino acid modifications

Modified residue

400

1

Phosphoserine Ref.50

Modified residue

401

1

Phosphotyrosine Ref.50

Modified residue

407

1

Phosphoserine Ref.50

Modified residue

992

1

Phosphotyrosine; by autocatalysis Probable

Modified residue

999

1

Phosphotyrosine; by autocatalysis

Modified residue

1011

1

Phosphotyrosine; by autocatalysis Probable

Modified residue

1064

1

Phosphoserine Ref.52

Modified residue

1112

1

N6-acetyllysine Ref.54

Modified residue

1185

1

Phosphotyrosine; by autocatalysis Ref.17 Ref.46

Modified residue

1189

1

Phosphotyrosine; by autocatalysis Ref.17 Ref.42 Ref.46 Ref.48

Modified residue

1190

1

Phosphotyrosine; by autocatalysis Ref.17 Ref.46

Modified residue

1348

1

Phosphoserine Ref.52

Modified residue

1354

1

Phosphoserine Ref.49

Modified residue

1355

1

Phosphotyrosine; by autocatalysis

Modified residue

1361

1

Phosphotyrosine; by autocatalysis

Modified residue

1379

1

Phosphoserine Ref.52

Glycosylation

43

1

N-linked (GlcNAc...) Ref.2

Glycosylation

52

1

N-linked (GlcNAc...) Potential

Glycosylation

105

1

N-linked (GlcNAc...) Potential

Glycosylation

138

1

N-linked (GlcNAc...) Potential

Glycosylation

242

1

N-linked (GlcNAc...) Ref.51

Glycosylation

282

1

N-linked (GlcNAc...) Potential

Glycosylation

322

1

N-linked (GlcNAc...) Potential

Glycosylation

364

1

N-linked (GlcNAc...) Potential

Glycosylation

424

1

N-linked (GlcNAc...) Potential

Glycosylation

445

1

N-linked (GlcNAc...) Ref.53

Glycosylation

541

1

N-linked (GlcNAc...) Ref.23 Ref.51

Glycosylation

633

1

N-linked (GlcNAc...) Potential

Glycosylation

651

1

N-linked (GlcNAc...) Potential

Glycosylation

698

1

N-linked (GlcNAc...) Potential

Glycosylation

769

1

N-linked (GlcNAc...) Ref.2

Glycosylation

782

1

N-linked (GlcNAc...) Potential

Glycosylation

920

1

N-linked (GlcNAc...) Ref.53

Glycosylation

933

1

N-linked (GlcNAc...) Potential

Disulfide bond

219 ↔ 228

By similarity

Disulfide bond

223 ↔ 234

By similarity

Disulfide bond

235 ↔ 243

By similarity

Disulfide bond

239 ↔ 252

By similarity

Disulfide bond

255 ↔ 264

By similarity

Disulfide bond

268 ↔ 280

By similarity

Disulfide bond

286 ↔ 293

By similarity

Disulfide bond

301 ↔ 311

By similarity

Disulfide bond

315 ↔ 328

By similarity

Disulfide bond

331 ↔ 335

By similarity

Disulfide bond

462 ↔ 495

Ref.23

Disulfide bond

551

Interchain Ref.23

Natural variations

Alternative sequence

745 – 756

12

Missing in isoform Short.

VSP_002898

Natural variant

2

1

A → G. Ref.1 Ref.2 Ref.4 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Corresponds to variant rs7508518 [ dbSNP | Ensembl ].

VAR_058395

Natural variant

42

1

N → K in RMS; impairs transport to the plasma membrane and reduces the affinity to bind insulin. Ref.63 Ref.64

VAR_004079

Natural variant

55

1

V → A in LEPRCH; Verona-1. Ref.69

VAR_004080

Natural variant

58

1

G → R in LEPRCH; Helmond; inhibits processing and transport. Ref.72
Corresponds to variant rs52836744 [ dbSNP | Ensembl ].

VAR_004081

Natural variant

86

1

D → G in IRAN type A. Ref.94

VAR_015907

Natural variant

89

1

L → P in IRAN type A. Ref.94

VAR_015908

Natural variant

113

1

R → P in LEPRCH; Atlanta-1; abolishes insulin binding. Ref.82 Ref.102

VAR_004082

Natural variant

119

1

A → V in LEPRCH; markedly impairs insulin binding. Ref.102

VAR_015909

Natural variant

120

1

L → Q in LEPRCH; inhibits receptor processing. Ref.104

VAR_031518

Natural variant

146

1

I → M in LEPRCH; mild. Ref.81 Ref.88

VAR_015539

Natural variant

167

1

V → L in IRAN type A. Ref.99

VAR_015910

Natural variant

171

1

Y → H. Ref.1
Corresponds to variant rs1051692 [ dbSNP | Ensembl ].

VAR_058396

Natural variant

220

1

P → L in Ins resistance; severe. Ref.78

VAR_004083

Natural variant

228

1

C → R in a gastric adenocarcinoma sample; somatic mutation. Ref.107

VAR_041429

Natural variant

236

1

H → R in LEPRCH; Winnipeg; in one patient with in RMS heterozygous compound with S-386; may impair receptor processing. Ref.64 Ref.106

VAR_004084

Natural variant

260

1

L → P in LEPRCH; Geldeimalsen. Ref.60

VAR_004085

Natural variant

279

1

R → C in IRAN type A; inhibits receptor internalization. Ref.101

VAR_015540

Natural variant

279

1

R → H in IRAN type A; interferes with receptor processing. Ref.104

VAR_031519

Natural variant

280

1

C → Y in IRAN type A. Ref.100

VAR_015911

Natural variant

301

1

C → Y in LEPRCH. Ref.97

VAR_015912

Natural variant

308

1

Missing in LEPRCH; abolishes insulin binding.

VAR_015913

Natural variant

350

1

S → L in RMS and LEPRCH. Ref.84 Ref.104

VAR_015914

Natural variant

362

1

Missing in LEPRCH.

VAR_015541

Natural variant

386

1

G → S in RMS; may impair receptor processing. Ref.106

VAR_031520

Natural variant

393

1

G → R in LEPRCH; Verona-1. Ref.69

VAR_004086

Natural variant

409

1

F → V in IRAN type A. Ref.80

VAR_004087

Natural variant

439

1

W → S in LEPRCH; impairs transport of the receptor to the cell surface. Ref.86

VAR_015542

Natural variant

448

1

I → T. Ref.1
Corresponds to variant rs1051691 [ dbSNP | Ensembl ].

VAR_015915

Natural variant

458

1

N → D in LEPRCH; partially inhibits receptor processing and autophosphorylation; strongly impairs ERK phosphorylation; induces wild-type levels of IRS-1 phosphorylation. Ref.104

VAR_031521

Natural variant

487

1

K → E in LEPRCH; ARK-1. Ref.59
Corresponds to variant rs28933083 [ dbSNP | Ensembl ].

VAR_004088

Natural variant

489

1

N → S in IRAN type A. Ref.64
Corresponds to variant rs28933085 [ dbSNP | Ensembl ].

VAR_004089

Natural variant

492

1

Q → K. Ref.1
Corresponds to variant rs1131851 [ dbSNP | Ensembl ].

VAR_015916

Natural variant

695

1

Q → R. Ref.107
Corresponds to variant rs55906835 [ dbSNP | Ensembl ].

VAR_041430

Natural variant

762

1

R → S in IRAN type A. Ref.58

VAR_004090

Natural variant

811

1

G → S. Ref.107
Corresponds to variant rs35045353 [ dbSNP | Ensembl ].

VAR_041431

Natural variant

830

1

P → L.
Corresponds to variant rs2162771 [ dbSNP | Ensembl ].

VAR_055986

Natural variant

858

1

T → A in NIDDM. Ref.89

VAR_015917

Natural variant

925

1

I → T in LEPRCH; abolishes insulin binding. Ref.102

VAR_015918

Natural variant

926

1

R → W in LEPRCH; markedly impairs insulin binding. Ref.102

VAR_015919

Natural variant

937

1

T → M in LEPRCH; impaired receptor processing. Ref.95

VAR_015920

Natural variant

997

1

P → T in RMS; reduces insulin binding. Ref.102

VAR_015921

Natural variant

1012

1

V → M Rare polymorphism. Ref.74 Ref.76 Ref.84 Ref.93 Ref.107
Corresponds to variant rs1799816 [ dbSNP | Ensembl ].

VAR_004091

Natural variant

1020

1

R → Q in IRAN type A. Ref.67

VAR_004092

Natural variant

1023

1

I → F. Ref.91

VAR_015922

Natural variant

1035

1

G → V in IRAN type A. Ref.61

VAR_004093

Natural variant

1055

1

A → V in IRAN type A. Ref.99

VAR_015923

Natural variant

1065

1

L → V. Ref.107
Corresponds to variant rs56395521 [ dbSNP | Ensembl ].

VAR_041432

Natural variant

1075

1

A → D in IRAN type A. Ref.75

VAR_004094

Natural variant

1095

1

K → E in a NIDDM subject. Ref.66

VAR_015924

Natural variant

1119

1

R → W in LEPRCH. Ref.96 Ref.104

VAR_015925

Natural variant

1143

1

I → T in RMS; reduces insulin binding. Ref.98 Ref.102

VAR_015926

Natural variant

1158

1

R → Q in NIDDM. Ref.73

VAR_015927

Natural variant

1158

1

R → W in RMS; abolishes insulin binding. Ref.98 Ref.102

VAR_015928

Natural variant

1161

1

A → T in IRAN type A. Ref.62
Corresponds to variant rs28933084 [ dbSNP | Ensembl ].

VAR_004095

Natural variant

1162

1

A → E in IRAN type A; impairs proteolytic processing. Ref.79

VAR_004096

Natural variant

1180

1

M → I in a patient with insulin resistance. Ref.68

VAR_004097

Natural variant

1191

1

R → Q in NIDDM. Ref.70

VAR_004098

Natural variant

1201

1

R → Q in HHF5 and IRAN type A; interferes with kinase activation by insulin. Ref.83 Ref.85 Ref.105
Corresponds to variant rs28933086 [ dbSNP | Ensembl ].

VAR_015929

Natural variant

1201

1

R → W in LEPRCH and RMS; reduces insulin binding possibly due to reduced receptor levels on the cell surface. Ref.97 Ref.102

VAR_015930

Natural variant

1205

1

P → L in IRAN type A; moderate. Ref.71 Ref.84

VAR_004099

Natural variant

1206

1

E → D in IRAN type A; accelerates degradation of the protein and impairs kinase activity. Ref.87

VAR_015931

Natural variant

1206

1

E → K in LEPRCH. Ref.96

VAR_015932

Natural variant

1220

1

W → L in IRAN type A; accelerates degradation of the protein and impairs kinase activity. Ref.77 Ref.87
Corresponds to variant rs52800171 [ dbSNP | Ensembl ].

VAR_004100

Natural variant

1227

1

W → S in IRAN type A. Ref.65

VAR_004101

Natural variant

1282

1

T → A. Ref.107
Corresponds to variant rs55875349 [ dbSNP | Ensembl ].

VAR_041433

Natural variant

1361

1

Y → C. Ref.89
Corresponds to variant rs13306449 [ dbSNP | Ensembl ].

VAR_015933

Natural variant

1378

1

R → Q in IRAN type A. Ref.84
Corresponds to variant rs52826008 [ dbSNP | Ensembl ].

VAR_015934

Experimental info

Mutagenesis

991

1

L → A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. Ref.26

Mutagenesis

992

1

Y → A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. Ref.26

Mutagenesis

996 – 997

2

NP → AA: Abolishes interaction with IRS1. Severely disrupts, but does not abolish interaction with SHC1. Ref.26 Ref.27

Mutagenesis

996

1

N → A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. Ref.26 Ref.27

Mutagenesis

997

1

P → A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. Ref.26 Ref.27

Mutagenesis

998

1

E → A: Does not affect interaction with IRS1, SHC1 or PIK3R1. Ref.27

Mutagenesis

999

1

Y → E: Abolishes interaction with IRS1 and SHC1. Ref.21 Ref.26 Ref.27 Ref.29

Mutagenesis

999

1

Y → F: Has no effect on insulin-stimulated autophosphorylation, but inhibits the biological activity of the receptor. Abolishes interaction with IRS1 and almost completely prevents interaction with SHC1. Has no effect on interaction with PIK3R1. Abolishes interaction with STAT5B. Ref.21 Ref.26 Ref.27 Ref.29

Mutagenesis

1000

1

L → A or R: Severely reduces interaction with SHC1. Has no effect on interaction with IRS1. Ref.26

Mutagenesis

1002

1

A → D: Reduces interaction with IRS1 but has no effect on interaction with SHC1. Ref.26

Mutagenesis

1057

1

K → A: Abolishes the kinase activity and abolishes interaction with IRS1, SHC1, GRB7 and PIK3R1. Ref.20 Ref.27 Ref.35

Mutagenesis

1057

1

K → M or R: Abolishes the kinase activity. Ref.20 Ref.27 Ref.35

Mutagenesis

1189

1

Y → F: Reduced interaction with GRB7. Ref.35

Mutagenesis

1190

1

Y → F: Strongly reduced interaction with GRB7. Ref.35

Sequence conflict

601

1

D → N AA sequence Ref.19

Sequence conflict

830

1

P → E AA sequence Ref.19

Sequence conflict

1278

1

K → N in CAA26096. Ref.2

Secondary structure

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1382

Helix Strand Turn

Details...

Beta strand

33 – 42

10

Helix

45 – 50

6

Beta strand

53 – 65

13

Helix

70 – 72

3

Turn

73 – 75

3

Beta strand

83 – 86

4

Beta strand

88 – 93

6

Turn

100 – 102

3

Beta strand

118 – 124

7

Beta strand

141 – 149

9

Helix

160 – 162

3

Beta strand

171 – 175

5

Helix

176 – 178

3

Turn

187 – 192

6

Beta strand

199 – 201

3

Beta strand

204 – 206

3

Beta strand

209 – 211

3

Helix

221 – 223

3

Beta strand

243 – 247

5

Beta strand

251 – 260

10

Beta strand

263 – 267

5

Beta strand

273 – 275

3

Turn

276 – 278

3

Beta strand

279 – 281

3

Helix

283 – 295

13

Beta strand

298 – 300

3

Beta strand

305 – 307

3

Beta strand

310 – 314

5

Beta strand

319 – 321

3

Beta strand

327 – 330

4

Beta strand

332 – 334

3

Beta strand

338 – 348

11

Helix

351 – 355

5

Turn

356 – 359

4

Beta strand

361 – 369

9

Helix

377 – 385

9

Beta strand

390 – 393

4

Beta strand

395 – 399

5

Beta strand

404 – 406

3

Turn

422 – 424

3

Beta strand

425 – 430

6

Turn

441 – 443

3

Beta strand

452 – 458

7

Helix

463 – 472

10

Turn

476 – 478

3

Turn

481 – 483

3

Beta strand

486 – 490

5

Beta strand

513 – 515

3

Beta strand

521 – 523

3

Beta strand

527 – 530

4

Beta strand

534 – 536

3

Turn

539 – 541

3

Beta strand

564 – 567

4

Beta strand

572 – 574

3

Beta strand

577 – 580

4

Beta strand

591 – 595

5

Beta strand

626 – 632

7

Beta strand

634 – 636

3

Beta strand

638 – 643

6

Beta strand

648 – 651

4

Beta strand

653 – 656

4

Beta strand

659 – 662

4

Beta strand

672 – 674

3

Beta strand

805 – 809

5

Beta strand

817 – 820

4

Beta strand

823 – 826

4

Beta strand

828 – 831

4

Beta strand

840 – 843

4

Beta strand

861 – 865

5

Beta strand

881 – 884

4

Beta strand

889 – 893

5

Beta strand

902 – 904

3

Beta strand

918 – 921

4

Beta strand

927 – 929

3

Turn

1014 – 1016

3

Helix

1020 – 1022

3

Beta strand

1023 – 1031

9

Beta strand

1033 – 1043

11

Beta strand

1050 – 1058

9

Helix

1065 – 1078

14

Beta strand

1089 – 1093

5

Beta strand

1095 – 1098

4

Beta strand

1100 – 1104

5

Helix

1111 – 1117

7

Helix

1133 – 1152

20

Helix

1162 – 1164

3

Beta strand

1165 – 1167

3

Beta strand

1173 – 1175

3

Helix

1200 – 1202

3

Helix

1205 – 1210

6

Helix

1215 – 1230

16

Turn

1236 – 1239

4

Helix

1242 – 1250

9

Helix

1263 – 1272

10

Helix

1277 – 1279

3

Helix

1283 – 1290

8

Helix

1291 – 1293

3

Helix

1298 – 1301

4

Helix

1307 – 1309

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long (HIR-B) [UniParc]. Last modified October 5, 2010. Version 4. Checksum: 709A955660739066	FASTA	1,382	156,333
	10 20 30 40 50 60 MATGGRRGAA AAPLLVAVAA LLLGAAGHLY PGEVCPGMDI RNNLTRLHEL ENCSVIEGHL 70 80 90 100 110 120 QILLMFKTRP EDFRDLSFPK LIMITDYLLL FRVYGLESLK DLFPNLTVIR GSRLFFNYAL 130 140 150 160 170 180 VIFEMVHLKE LGLYNLMNIT RGSVRIEKNN ELCYLATIDW SRILDSVEDN YIVLNKDDNE 190 200 210 220 230 240 ECGDICPGTA KGKTNCPATV INGQFVERCW THSHCQKVCP TICKSHGCTA EGLCCHSECL 250 260 270 280 290 300 GNCSQPDDPT KCVACRNFYL DGRCVETCPP PYYHFQDWRC VNFSFCQDLH HKCKNSRRQG 310 320 330 340 350 360 CHQYVIHNNK CIPECPSGYT MNSSNLLCTP CLGPCPKVCH LLEGEKTIDS VTSAQELRGC 370 380 390 400 410 420 TVINGSLIIN IRGGNNLAAE LEANLGLIEE ISGYLKIRRS YALVSLSFFR KLRLIRGETL 430 440 450 460 470 480 EIGNYSFYAL DNQNLRQLWD WSKHNLTITQ GKLFFHYNPK LCLSEIHKME EVSGTKGRQE 490 500 510 520 530 540 RNDIALKTNG DQASCENELL KFSYIRTSFD KILLRWEPYW PPDFRDLLGF MLFYKEAPYQ 550 560 570 580 590 600 NVTEFDGQDA CGSNSWTVVD IDPPLRSNDP KSQNHPGWLM RGLKPWTQYA IFVKTLVTFS 610 620 630 640 650 660 DERRTYGAKS DIIYVQTDAT NPSVPLDPIS VSNSSSQIIL KWKPPSDPNG NITHYLVFWE 670 680 690 700 710 720 RQAEDSELFE LDYCLKGLKL PSRTWSPPFE SEDSQKHNQS EYEDSAGECC SCPKTDSQIL 730 740 750 760 770 780 KELEESSFRK TFEDYLHNVV FVPRKTSSGT GAEDPRPSRK RRSLGDVGNV TVAVPTVAAF 790 800 810 820 830 840 PNTSSTSVPT SPEEHRPFEK VVNKESLVIS GLRHFTGYRI ELQACNQDTP EERCSVAAYV 850 860 870 880 890 900 SARTMPEAKA DDIVGPVTHE IFENNVVHLM WQEPKEPNGL IVLYEVSYRR YGDEELHLCV 910 920 930 940 950 960 SRKHFALERG CRLRGLSPGN YSVRIRATSL AGNGSWTEPT YFYVTDYLDV PSNIAKIIIG 970 980 990 1000 1010 1020 PLIFVFLFSV VIGSIYLFLR KRQPDGPLGP LYASSNPEYL SASDVFPCSV YVPDEWEVSR 1030 1040 1050 1060 1070 1080 EKITLLRELG QGSFGMVYEG NARDIIKGEA ETRVAVKTVN ESASLRERIE FLNEASVMKG 1090 1100 1110 1120 1130 1140 FTCHHVVRLL GVVSKGQPTL VVMELMAHGD LKSYLRSLRP EAENNPGRPP PTLQEMIQMA 1150 1160 1170 1180 1190 1200 AEIADGMAYL NAKKFVHRDL AARNCMVAHD FTVKIGDFGM TRDIYETDYY RKGGKGLLPV 1210 1220 1230 1240 1250 1260 RWMAPESLKD GVFTTSSDMW SFGVVLWEIT SLAEQPYQGL SNEQVLKFVM DGGYLDQPDN 1270 1280 1290 1300 1310 1320 CPERVTDLMR MCWQFNPKMR PTFLEIVNLL KDDLHPSFPE VSFFHSEENK APESEELEME 1330 1340 1350 1360 1370 1380 FEDMENVPLD RSSHCQREEA GGRDGGSSLG FKRSYEEHIP YTHMNGGKKN GRILTLPRSN PS
	Isoform Short (HIR-A) [UniParc]. Checksum: A396F39279C2764D	FASTA	1,370	155,146
	10 20 30 40 50 60 MATGGRRGAA AAPLLVAVAA LLLGAAGHLY PGEVCPGMDI RNNLTRLHEL ENCSVIEGHL 70 80 90 100 110 120 QILLMFKTRP EDFRDLSFPK LIMITDYLLL FRVYGLESLK DLFPNLTVIR GSRLFFNYAL 130 140 150 160 170 180 VIFEMVHLKE LGLYNLMNIT RGSVRIEKNN ELCYLATIDW SRILDSVEDN YIVLNKDDNE 190 200 210 220 230 240 ECGDICPGTA KGKTNCPATV INGQFVERCW THSHCQKVCP TICKSHGCTA EGLCCHSECL 250 260 270 280 290 300 GNCSQPDDPT KCVACRNFYL DGRCVETCPP PYYHFQDWRC VNFSFCQDLH HKCKNSRRQG 310 320 330 340 350 360 CHQYVIHNNK CIPECPSGYT MNSSNLLCTP CLGPCPKVCH LLEGEKTIDS VTSAQELRGC 370 380 390 400 410 420 TVINGSLIIN IRGGNNLAAE LEANLGLIEE ISGYLKIRRS YALVSLSFFR KLRLIRGETL 430 440 450 460 470 480 EIGNYSFYAL DNQNLRQLWD WSKHNLTITQ GKLFFHYNPK LCLSEIHKME EVSGTKGRQE 490 500 510 520 530 540 RNDIALKTNG DQASCENELL KFSYIRTSFD KILLRWEPYW PPDFRDLLGF MLFYKEAPYQ 550 560 570 580 590 600 NVTEFDGQDA CGSNSWTVVD IDPPLRSNDP KSQNHPGWLM RGLKPWTQYA IFVKTLVTFS 610 620 630 640 650 660 DERRTYGAKS DIIYVQTDAT NPSVPLDPIS VSNSSSQIIL KWKPPSDPNG NITHYLVFWE 670 680 690 700 710 720 RQAEDSELFE LDYCLKGLKL PSRTWSPPFE SEDSQKHNQS EYEDSAGECC SCPKTDSQIL 730 740 750 760 770 780 KELEESSFRK TFEDYLHNVV FVPRPSRKRR SLGDVGNVTV AVPTVAAFPN TSSTSVPTSP 790 800 810 820 830 840 EEHRPFEKVV NKESLVISGL RHFTGYRIEL QACNQDTPEE RCSVAAYVSA RTMPEAKADD 850 860 870 880 890 900 IVGPVTHEIF ENNVVHLMWQ EPKEPNGLIV LYEVSYRRYG DEELHLCVSR KHFALERGCR 910 920 930 940 950 960 LRGLSPGNYS VRIRATSLAG NGSWTEPTYF YVTDYLDVPS NIAKIIIGPL IFVFLFSVVI 970 980 990 1000 1010 1020 GSIYLFLRKR QPDGPLGPLY ASSNPEYLSA SDVFPCSVYV PDEWEVSREK ITLLRELGQG 1030 1040 1050 1060 1070 1080 SFGMVYEGNA RDIIKGEAET RVAVKTVNES ASLRERIEFL NEASVMKGFT CHHVVRLLGV 1090 1100 1110 1120 1130 1140 VSKGQPTLVV MELMAHGDLK SYLRSLRPEA ENNPGRPPPT LQEMIQMAAE IADGMAYLNA 1150 1160 1170 1180 1190 1200 KKFVHRDLAA RNCMVAHDFT VKIGDFGMTR DIYETDYYRK GGKGLLPVRW MAPESLKDGV 1210 1220 1230 1240 1250 1260 FTTSSDMWSF GVVLWEITSL AEQPYQGLSN EQVLKFVMDG GYLDQPDNCP ERVTDLMRMC 1270 1280 1290 1300 1310 1320 WQFNPKMRPT FLEIVNLLKD DLHPSFPEVS FFHSEENKAP ESEELEMEFE DMENVPLDRS 1330 1340 1350 1360 1370 SHCQREEAGG RDGGSSLGFK RSYEEHIPYT HMNGGKKNGR ILTLPRSNPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling." Ebina Y., Ellis L., Jarnagin K., Edery M., Graf L., Clauser E., Ou J.-H., Masiarz F., Kan Y.W., Goldfine I.D., Roth R.A., Rutter W.J. Cell 40:747-758(1985) [PubMed: 2859121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANTS GLY-2; HIS-171; THR-448 AND LYS-492.
[2]	"Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes." Ullrich A., Bell J.R., Chen E.Y., Herrera R., Petruzzelli L.M., Dull T.J., Gray A., Coussens L., Liao Y.-C., Tsubokawa M., Mason A., Seeburg P.H., Grunfeld C., Rosen O.M., Ramachandran J. Nature 313:756-761(1985) [PubMed: 2983222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), PROTEIN SEQUENCE OF 28-49 AND 763-782, GLYCOSYLATION AT ASN-43 AND ASN-769, VARIANT GLY-2.
[3]	Chen E.Y. Submitted (JUL-1985) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 899-900.
[4]	"Human insulin-receptor gene. Partial sequence and amplification of exons by polymerase chain reaction." Seino S., Seino M., Bell G.I. Diabetes 39:123-128(1990) [PubMed: 2210055] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-2. Tissue: Fetal liver.
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT), VARIANT GLY-2.
[7]	"Characterization of the promoter region of the human insulin receptor gene. Evidence for promoter activity." Araki E., Shimada F., Uzawa H., Mori M., Ebina Y. J. Biol. Chem. 262:16186-16191(1987) [PubMed: 3680248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, VARIANT GLY-2.
[8]	"Characterization of the promoter region of the human insulin receptor gene." Araki E., Shimada F., Fukushima H., Mori M., Shichiri M., Ebina Y. Diabetes Res. Clin. Pract. 7:S31-S33(1989) [PubMed: 2806055] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, VARIANT GLY-2.
[9]	"Characterization of the promoter region and 3' end of the human insulin receptor gene." Tewari D.S., Cook D.M., Taub R. J. Biol. Chem. 264:16238-16245(1989) [PubMed: 2777789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, VARIANT GLY-2.
[10]	"Structural and functional analysis of the insulin receptor promoter." McKeon C., Moncada V., Pham T., Salvatore P., Kadowaki T., Accili D., Taylor S.I. Mol. Endocrinol. 4:647-656(1990) [PubMed: 2280779] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, VARIANT GLY-2. Tissue: Skin fibroblast.
[11]	"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: PROTEIN SEQUENCE OF 28-44; 192-205; 299-314; 610-627 AND 763-780, ENZYME REGULATION, SUBUNIT. Tissue: Placenta.
[12]	"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 28-45 AND 763-782, FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH IGF1R. Tissue: Placenta.
[13]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 538-1382 (ISOFORM SHORT). Tissue: Brain.
[14]	"Alternative splicing of human insulin receptor messenger RNA." Seino S., Bell G.I. Biochem. Biophys. Res. Commun. 159:312-316(1989) [PubMed: 2538124] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 728-772 (ISOFORM LONG), ALTERNATIVE SPLICING.
[15]	"Functionally distinct insulin receptors generated by tissue-specific alternative splicing." Mosthaf L., Grako K., Dull T.J., Coussens L., Ullrich A., McClain D.A. EMBO J. 9:2409-2413(1990) [PubMed: 2369896] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 744-823 (ISOFORM LONG), TISSUE SPECIFICITY, LIGAND-BINDING, AUTOPHOSPHORYLATION.
[16]	"Molecular and clinical characterization of an insertional polymorphism of the insulin-receptor gene." Elbein S.C. Diabetes 38:737-743(1989) [PubMed: 2566545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 895-1085.
[17]	"Studies on the autophosphorylation of the insulin receptor from human placenta. Analysis of the sites phosphorylated by two-dimensional peptide mapping." Tavare J.M., Denton R.M. Biochem. J. 252:607-615(1988) [PubMed: 3166375] [Abstract] Cited for: PROTEIN SEQUENCE OF 927-956; 981-1019; 1182-1194 AND 1352-1369, AUTOPHOSPHORYLATION. Tissue: Placenta.
[18]	"Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor." Taira M., Taira M., Hashimoto N., Shimada F., Suzuki Y., Kanatsuka A., Nakamura F., Ebina Y., Tatibana M., Makino H. Science 245:63-66(1989) [PubMed: 2544997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1006-1123.
[19]	"Partial amino acid sequence analyses of human placental insulin receptor." Fujita-Yamaguchi Y., Hawke D., Shively J.E., Choi S. Protein Seq. Data Anal. 1:3-6(1987) [PubMed: 3447155] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[20]	"Replacement of lysine residue 1030 in the putative ATP-binding region of the insulin receptor abolishes insulin- and antibody-stimulated glucose uptake and receptor kinase activity." Ebina Y., Araki E., Taira M., Shimada F., Mori M., Craik C.S., Siddle K., Pierce S.B., Roth R.A., Rutter W.J. Proc. Natl. Acad. Sci. U.S.A. 84:704-708(1987) [PubMed: 3101064] [Abstract] Cited for: MUTAGENESIS OF LYS-1057.
[21]	"Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity." White M.F., Livingston J.N., Backer J.M., Lauris V., Dull T.J., Ullrich A., Kahn C.R. Cell 54:641-649(1988) [PubMed: 2842060] [Abstract] Cited for: MUTAGENESIS OF TYR-999.
[22]	"Analysis of the order of autophosphorylation of human insulin receptor tyrosines 1158, 1162 and 1163." Dickens M., Tavare J.M. Biochem. Biophys. Res. Commun. 186:244-250(1992) [PubMed: 1321605] [Abstract] Cited for: AUTOPHOSPHORYLATION.
[23]	"Identification of a disulfide bridge connecting the alpha-subunits of the extracellular domain of the insulin receptor." Schaeffer L., Ljungqvist L. Biochem. Biophys. Res. Commun. 189:650-653(1992) [PubMed: 1472036] [Abstract] Cited for: DISULFIDE BONDS, GLYCOSYLATION AT ASN-541.
[24]	"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 IGF1R.
[25]	"Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor." Van Horn D.J., Myers M.G. Jr., Backer J.M. J. Biol. Chem. 269:29-32(1994) [PubMed: 8276809] [Abstract] Cited for: FUNCTION, INTERACTION WITH PIK3R1.
[26]	"Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains." He W., O'Neill T.J., Gustafson T.A. J. Biol. Chem. 270:23258-23262(1995) [PubMed: 7559478] [Abstract] Cited for: INTERACTION WITH IRS1 AND SHC1, MUTAGENESIS OF LEU-991; TYR-992; ASN-996; 996-ASN-PRO-997; PRO-997; TYR-999; LEU-1000 AND ALA-1002.
[27]	"Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain." Gustafson T.A., He W., Craparo A., Schaub C.D., O'Neill T.J. Mol. Cell. Biol. 15:2500-2508(1995) [PubMed: 7537849] [Abstract] Cited for: INTERACTION WITH IRS1; SHC1 AND PIK3R1, MUTAGENESIS OF ASN-996; PRO-997; GLU-998; TYR-999 AND LYS-1057.
[28]	"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 IGF1R, TISSUE SPECIFICITY.
[29]	"Identification of Stat 5B as a substrate of the insulin receptor." Sawka-Verhelle D., Filloux C., Tartare-Deckert S., Mothe I., Van Obberghen E. Eur. J. Biochem. 250:411-417(1997) [PubMed: 9428692] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STAT5B, MUTAGENESIS OF TYR-999, INTERACTION WITH STAT5B; IRS1 AND IRS2.
[30]	"Functional association between the insulin receptor and the transmembrane protein-tyrosine phosphatase LAR in intact cells." Ahmad F., Goldstein B.J. J. Biol. Chem. 272:448-457(1997) [PubMed: 8995282] [Abstract] Cited for: INTERACTION WITH PTPRF.
[31]	"Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and is tyrosine-phosphorylated in the presence of insulin." Bandyopadhyay D., Kusari A., Kenner K.A., Liu F., Chernoff J., Gustafson T.A., Kusari J. J. Biol. Chem. 272:1639-1645(1997) [PubMed: 8999839] [Abstract] Cited for: INTERACTION WITH PTPRE, DEPHOSPHORYLATION BY PTPRE.
[32]	"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 IGF1R, TISSUE SPECIFICITY.
[33]	"Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells." Frasca F., Pandini G., Scalia P., Sciacca L., Mineo R., Costantino A., Goldfine I.D., Belfiore A., Vigneri R. Mol. Cell. Biol. 19:3278-3288(1999) [PubMed: 10207053] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION AS RECEPTOR FOR IGFII (ISOFORM SHORT).
[34]	"Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit." Maddux B.A., Goldfine I.D. Diabetes 49:13-19(2000) [PubMed: 10615944] [Abstract] Cited for: INTERACTION WITH ENPP1, ENZYME REGULATION.
[35]	"Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2." Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F. Oncogene 19:2052-2059(2000) [PubMed: 10803466] [Abstract] Cited for: INTERACTION WITH GRB7, MUTAGENESIS OF LYS-1057; TYR-1189 AND TYR-1190.
[36]	"Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B." Lin W.-H., Huang C.-J., Liu M.-W., Chang H.-M., Chen Y.-J., Tai T.-Y., Chuang L.-M. Genomics 74:12-20(2001) [PubMed: 11374898] [Abstract] Cited for: INTERACTION WITH SORBS1.
[37]	"Inhibition of insulin receptor catalytic activity by the molecular adapter Grb14." Bereziat V., Kasus-Jacobi A., Perdereau D., Cariou B., Girard J., Burnol A.F. J. Biol. Chem. 277:4845-4852(2002) [PubMed: 11726652] [Abstract] Cited for: INTERACTION WITH GRB14, ENZYME REGULATION.
[38]	"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 IGF1R.
[39]	"Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor." Wick K.R., Werner E.D., Langlais P., Ramos F.J., Dong L.Q., Shoelson S.E., Liu F. J. Biol. Chem. 278:8460-8467(2003) [PubMed: 12493740] [Abstract] Cited for: INTERACTION WITH GRB10, ENZYME REGULATION.
[40]	"Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans." Banks A.S., Li J., McKeag L., Hribal M.L., Kashiwada M., Accili D., Rothman P.B. J. Clin. Invest. 115:2462-2471(2005) [PubMed: 16127460] [Abstract] Cited for: INTERACTION WITH SOCS7.
[41]	"Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling." Fiory F., Alberobello A.T., Miele C., Oriente F., Esposito I., Corbo V., Ruvo M., Tizzano B., Rasmussen T.E., Gammeltoft S., Formisano P., Beguinot F. Mol. Cell. Biol. 25:10803-10814(2005) [PubMed: 16314505] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF PDPK1, INTERACTION WITH PDPK1.
[42]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1189, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[43]	"Receptor-type protein tyrosine phosphatase epsilon (PTPepsilonM) is a negative regulator of insulin signaling in primary hepatocytes and liver." Nakagawa Y., Aoki N., Aoyama K., Shimizu H., Shimano H., Yamada N., Miyazaki H. Zool. Sci. 22:169-175(2005) [PubMed: 15738637] [Abstract] Cited for: DEPHOSPHORYLATION BY PTPRE.
[44]	"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 IGF1R.
[45]	"Critical nodes in signalling pathways: insights into insulin action." Taniguchi C.M., Emanuelli B., Kahn C.R. Nat. Rev. Mol. Cell Biol. 7:85-96(2006) [PubMed: 16493415] [Abstract] Cited for: REVIEW ON SIGNALING PATHWAYS.
[46]	"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-1185; TYR-1189 AND TYR-1190, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[47]	"Regulation of insulin receptor function." Youngren J.F. Cell. Mol. Life Sci. 64:873-891(2007) [PubMed: 17347799] [Abstract] Cited for: REVIEW ON REGULATION OF INSR FUNCTION.
[48]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1189, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[49]	"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 SER-1354, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[50]	"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-400; TYR-401 AND SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[51]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242 AND ASN-541, MASS SPECTROMETRY. Tissue: Liver.
[52]	"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 SER-1064; SER-1348 AND SER-1379, MASS SPECTROMETRY.
[53]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-445 AND ASN-920, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[54]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1112, MASS SPECTROMETRY.
[55]	"Crystal structure of the tyrosine kinase domain of the human insulin receptor." Hubbard S.R., Wei L., Ellis L., Hendrickson W.A. Nature 372:746-754(1994) [PubMed: 7997262] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1005-1310.
[56]	"Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog." Hubbard S.R. EMBO J. 16:5572-5581(1997) [PubMed: 9312016] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1005-1310.
[57]	"Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor." Hu J., Liu J., Ghirlando R., Saltiel A.R., Hubbard S.R. Mol. Cell 12:1379-1389(2003) [PubMed: 14690593] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH SH2B2.
[58]	"Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing." Yoshimasa Y., Seino S., Whittaker J., Kakehi T., Kosaki A., Kuzuya H., Imura H., Bell G.I., Steiner D.F. Science 240:784-787(1988) [PubMed: 3283938] [Abstract] Cited for: VARIANT IRAN TYPE A SER-762.
[59]	"Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance." Kadowaki T., Bevins C., Cama A., Ojamaa K., Marcus-Samuels B., Kadowaki H., Beitz L., McKeon C., Taylor S.I. Science 240:787-790(1988) [PubMed: 2834824] [Abstract] Cited for: VARIANT LEPRCH GLU-487.
[60]	"A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance." Klinkhamer M.P., Groen N.A., van der Zon G.C.M., Lindhout D., Sandkuyl L.A., Krans H.M.J., Moeller W., Maassen J.A. EMBO J. 8:2503-2507(1989) [PubMed: 2479553] [Abstract] Cited for: VARIANT LEPRCH PRO-260.
[61]	"Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor." Odawara M., Kadowaki T., Yamamoto R., Shibasaki Y., Tobe K., Accili D., Bevins C., Mikami Y., Matsuura N., Akanuma Y., Takaku F., Taylor S.I., Kasuga M. Science 245:66-68(1989) [PubMed: 2544998] [Abstract] Cited for: VARIANT IRAN TYPE A VAL-1035.
[62]	"A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance." Moller D.E., Yokota A., White M.F., Pazianos A.G., Flier J.S. J. Biol. Chem. 265:14979-14985(1990) [PubMed: 2168397] [Abstract] Cited for: VARIANT IRAN TYPE A THR-1161.
[63]	"Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding." Kadowaki T., Kadowaki H., Accili D., Taylor S.I. J. Biol. Chem. 265:19143-19150(1990) [PubMed: 2121734] [Abstract] Cited for: CHARACTERIZATION OF VARIANT RMS LYS-42.
[64]	"Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance." Kadowaki T., Kadowaki H., Rechler M.M., Serrano-Rios M., Roth J., Gorden P., Taylor S.I. J. Clin. Invest. 86:254-264(1990) [PubMed: 2365819] [Abstract] Cited for: VARIANT RMS LYS-42, VARIANT LEPRCH ARG-236, VARIANT IRAN TYPE A SER-489.
[65]	"Functional properties of a naturally occurring Trp1200-->Ser1200 mutation of the insulin receptor." Moller D.E., Yokota A., Ginsberg-Fellner F., Flier J.S. Mol. Endocrinol. 4:1183-1191(1990) [PubMed: 1963473] [Abstract] Cited for: VARIANT IRAN TYPE A SER-1227.
[66]	"Detection of mutations in insulin-receptor gene in NIDDM patients by analysis of single-stranded conformation polymorphisms." O'Rahilly S., Choi W.H., Patel P., Turner R.C., Flier J.S., Moller D.E. Diabetes 40:777-782(1991) [PubMed: 2040394] [Abstract] Cited for: VARIANT GLU-1095.
[67]	"Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles." Kusari J., Takata Y., Hatada E., Freidenberg G., Kolterman O., Olefsky J.M. J. Biol. Chem. 266:5260-5267(1991) [PubMed: 2002058] [Abstract] Cited for: VARIANT IRAN TYPE A GLN-1020.
[68]	"A mutation in the tyrosine kinase domain of the insulin receptor associated with insulin resistance in an obese woman." Cama A., de la Luz Sierra M., Ottini L., Kadowaki T., Gorden P., Imperato-Mcginley J., Taylor S.I. J. Clin. Endocrinol. Metab. 73:894-901(1991) [PubMed: 1890161] [Abstract] Cited for: VARIANT INS RESISTANCE ILE-1180.
[69]	"Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis." Barbetti F., Gejman P.V., Taylor S.I., Raben N., Cama A., Bonora E., Pizzo P., Moghetti P., Muggeo M., Roth J. Diabetes 41:408-415(1992) [PubMed: 1607067] [Abstract] Cited for: VARIANTS LEPRCH ALA-55 AND ARG-393.
[70]	"NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene." Cocozza S., Porcellini A., Riccardi G., Monticelli A., Condorelli G., Ferrara A., Pianese L., Miele C., Capaldo B., Beguinot F., Varrone S. Diabetes 41:521-526(1992) [PubMed: 1607076] [Abstract] Cited for: VARIANT NIDDM GLN-1191.
[71]	"Detection of mutations in the insulin receptor gene in patients with insulin resistance by analysis of single-stranded conformational polymorphisms." Kim H., Kadowaki H., Sakura H., Odawara M., Momomura K., Takahashi Y., Miyazaki Y., Ohtani T., Akanuma Y., Yazaki Y., Kasuga M., Taylor S.I., Kadowaki T. Diabetologia 35:261-266(1992) [PubMed: 1563582] [Abstract] Cited for: VARIANT IRAN TYPE A LEU-1205.
[72]	"An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport." van der Vorm E.R., van der Zon G.C.M., Moeller W., Krans H.M.J., Lindhout D., Maassen J.A. J. Biol. Chem. 267:66-71(1992) [PubMed: 1730625] [Abstract] Cited for: VARIANT LEPRCH ARG-58.
[73]	"Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes." Kasuga M., Kishimoto M., Hashiramoto M., Yonezawa K., Kazumi T., Hagino H., Shii K. Nihon Geka Gakkai Zasshi 93:968-971(1992) [PubMed: 1470163] [Abstract] Cited for: VARIANT NIDDM GLN-1158.
[74]	"Methionine for valine substitution in exon 17 of the insulin receptor gene in a pedigree with familial NIDDM." Elbein S.C., Sorensen L.K., Schumacher M.C. Diabetes 42:429-434(1993) [PubMed: 8432414] [Abstract] Cited for: VARIANT MET-1012.
[75]	"Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance." Haruta T., Takata Y., Iwanishi M., Maegawa H., Imamura T., Egawa K., Itazu T., Kobayashi M. Diabetes 42:1837-1844(1993) [PubMed: 8243830] [Abstract] Cited for: VARIANT IRAN TYPE A ASP-1075.
[76]	"Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli type, express normal insulin receptors." van der Vorm E.R., Kuipers A., Bonenkamp J.W., Kleijer W.J., van Maldergem L., Herwig J., Maassen J.A. Diabetologia 36:172-174(1993) [PubMed: 8458533] [Abstract] Cited for: VARIANT MET-1012.
[77]	"A mutation (Trp1193-->Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance." Iwanishi M., Haruta T., Takata Y., Ishibashi O., Sasaoka T., Egawa K., Imamura T., Naitou K., Itazu T., Kobayashi M. Diabetologia 36:414-422(1993) [PubMed: 8390949] [Abstract] Cited for: VARIANT INS RESISTANCE LEU-1220.
[78]	"Substitution of Leu for Pro-193 in the insulin receptor in a patient with a genetic form of severe insulin resistance." Carrera P., Cordera R., Ferrari M., Cremonesi L., Taramelli R., Andraghetti G., Carducci C., Dozio N., Pozza G., Taylor S.I., Micossi P., Barbetti F. Hum. Mol. Genet. 2:1437-1441(1993) [PubMed: 8242067] [Abstract] Cited for: VARIANT INS RESISTANCE LEU-220.
[79]	"Substitution of glutamic acid for alanine 1135 in the putative 'catalytic loop' of the tyrosine kinase domain of the human insulin receptor. A mutation that impairs proteolytic processing into subunits and inhibits receptor tyrosine kinase activity." Cama A., de la Luz Sierra M., Quon M.J., Ottini L., Gorden P., Taylor S.I. J. Biol. Chem. 268:8060-8069(1993) [PubMed: 8096518] [Abstract] Cited for: CHARACTERIZATION OF VARIANT IRAN TYPE A GLU-1162.
[80]	"Antibodies to the extracellular receptor domain restore the hormone-insensitive kinase and conformation of the mutant insulin receptor valine 382." Lebrun C., Baron V., Kaliman P., Gautier N., Dolais-Kitabgi J., Taylor S.I., Accili D., van Obberghen E. J. Biol. Chem. 268:11272-11277(1993) [PubMed: 8388389] [Abstract] Cited for: VARIANT IRAN TYPE A VAL-409.
[81]	"A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents." Al-Gazali L.I., Khalil M., Devadas K. J. Med. Genet. 30:470-475(1993) [PubMed: 8326490] [Abstract] Cited for: VARIANT LEPRCH MET-146.
[82]	"Activation of glucose transport by a natural mutation in the human insulin receptor." Longo N., Langley S.D., Griffin L.D., Elsas L.J. Proc. Natl. Acad. Sci. U.S.A. 90:60-64(1993) [PubMed: 8419945] [Abstract] Cited for: VARIANT LEPRCH PRO-113.
[83]	"Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance." Moller D.E., Cohen O., Yamaguchi Y., Assiz R., Grigorescu F., Eberle A., Morrow L.A., Moses A.C., Flier J.S. Diabetes 43:247-255(1994) [PubMed: 8288049] [Abstract] Cited for: VARIANT IRAN TYPE A GLN-1201.
[84]	"Molecular scanning of the insulin receptor gene in syndromes of insulin resistance." Krook A., Kumar S., Laing I., Boulton A.J., Wass J.A., O'Rahilly S. Diabetes 43:357-368(1994) [PubMed: 8314008] [Abstract] Cited for: VARIANT RMS SYNDROME LEU-350, VARIANTS IRAN TYPE A LEU-1205 AND GLN-1378, VARIANT MET-1012.
[85]	"Functional properties of a heterozygous mutation (Arg1174-->Gln) in the tyrosine kinase domain of the insulin receptor from a type A insulin resistant patient." Moritz W., Froesch E.R., Boeni-Schnetzler M. FEBS Lett. 351:276-280(1994) [PubMed: 8082780] [Abstract] Cited for: CHARACTERIZATION OF VARIANT IRAN TYPE A GLN-1201.
[86]	"A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding." van der Vorm E.R., Kuipers A., Kielkopf-Renner S., Krans H.M.J., Moller W., Maassen J.A. J. Biol. Chem. 269:14297-14302(1994) [PubMed: 8188715] [Abstract] Cited for: VARIANT LEPRCH SER-439.
[87]	"Two naturally occurring mutations in the kinase domain of insulin receptor accelerate degradation of the insulin receptor and impair the kinase activity." Imamura T., Takata Y., Sasaoka T., Takada Y., Morioka H., Haruta T., Sawa T., Iwanishi M., Hu Y.G., Suzuki Y., Hamada J., Kobayashi M. J. Biol. Chem. 269:31019-31027(1994) [PubMed: 7983039] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS IRAN TYPE A ASP-1206 AND LEU-1220.
[88]	"Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance." Hone J., Accili D., al-Gazali L.I., Lestringant G., Orban T., Taylor S.I. J. Med. Genet. 31:715-716(1994) [PubMed: 7815442] [Abstract] Cited for: VARIANT LEPRCH MET-146.
[89]	"Frequency of mutations of insulin receptor gene in Japanese patients with NIDDM." Kan M., Kanai F., Iida M., Jinnouchi H., Todaka M., Imanaka T., Ito K., Nishioka Y., Ohnishi T., Kamohara S., Hayashi H., Murakami T., Kagawa S., Sano H., Hashimoto N., Yoshida S., Makino H., Ebina Y. Diabetes 44:1081-1086(1995) [PubMed: 7657032] [Abstract] Cited for: VARIANT NIDDM ALA-858, VARIANT CYS-1361.
[90]	"Two mutations in the insulin receptor gene of a patient with leprechaunism: application to prenatal diagnosis." Longo N., Langley S.D., Griffin L.D., Elsas L.J. J. Clin. Endocrinol. Metab. 80:1496-1501(1995) [PubMed: 7538143] [Abstract] Cited for: VARIANT LEPRCH ASN-308 DEL.
[91]	"In-frame exon 2 deletion in insulin receptor RNA in a family with extreme insulin resistance in association with defective insulin binding: a case report." Moritz W., Boeni-Schnetzler M., Stevens W., Froesch E.R., Levy J.R. Eur. J. Endocrinol. 135:357-363(1996) [PubMed: 8890729] [Abstract] Cited for: VARIANT PHE-1023.
[92]	"Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization." Desbois-Mouthon C., Sert-Langeron C., Magre J., Oreal E., Blivet M.J., Flori E., Besmond C., Capeau J., Caron M. J. Clin. Endocrinol. Metab. 81:719-727(1996) [PubMed: 8636294] [Abstract] Cited for: VARIANT LEPRCH ASN-308 DEL.
[93]	"The Val985Met insulin-receptor variant in the Danish Caucasian population: lack of associations with non-insulin-dependent diabetes mellitus or insulin resistance." Hansen L., Hansen T., Clausen J.O., Echwald S.M., Urhammer S.A., Rasmussen S.K., Pedersen O. Am. J. Hum. Genet. 60:1532-1535(1997) [PubMed: 9199575] [Abstract] Cited for: VARIANT MET-1012.
[94]	"Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in type A syndrome of extreme insulin resistance." Rouard M., Macari F., Bouix O., Lautier C., Brun J.F., Lefebvre P., Renard E., Bringer J., Jaffiol C., Grigorescu F. Biochem. Biophys. Res. Commun. 234:764-768(1997) [PubMed: 9175790] [Abstract] Cited for: VARIANTS IRAN TYPE A GLY-86 AND PRO-89.
[95]	"Four mutant alleles of the insulin receptor gene associated with genetic syndromes of extreme insulin resistance." Kadowaki H., Takahashi Y., Ando A., Momomura K., Kaburagi Y., Quin J.D., MacCuish A.C., Koda N., Fukushima Y., Taylor S.I., Akanuma Y., Yazaki Y., Kadowaki T. Biochem. Biophys. Res. Commun. 237:516-520(1997) [PubMed: 9299395] [Abstract] Cited for: CHARACTERIZATION OF VARIANT LEPRCH MET-937.
[96]	"Molecular analysis of the insulin receptor gene for prenatal diagnosis of leprechaunism in two families." Desbois-Mouthon C., Girodon E., Ghanem N., Caron M., Pennerath A., Conteville P., Magre J., Besmond C., Goossens M., Capeau J., Amselem S. Prenat. Diagn. 17:657-663(1997) [PubMed: 9249867] [Abstract] Cited for: VARIANTS LEPRCH TRP-1119 AND LYS-1206.
[97]	"Multiple molecular mechanisms of insulin receptor dysfunction in a patient with Donohue syndrome." Whitehead J.P., Soos M.A., Jackson R., Tasic V., Kocova M., O'Rahilly S. Diabetes 47:1362-1364(1998) [PubMed: 9703342] [Abstract] Cited for: VARIANTS LEPRCH TYR-301 AND TRP-1201.
[98]	"Progressive decline in insulin levels in Rabson-Mendenhall syndrome." Longo N., Wang Y., Pasquali M. J. Clin. Endocrinol. Metab. 84:2623-2629(1999) [PubMed: 10443650] [Abstract] Cited for: VARIANTS RMS THR-1143 AND TRP-1158.
[99]	"Identification of three novel mutations in the insulin receptor gene in type A insulin resistant patients." Rique S., Nogues C., Ibanez L., Marcos M.V., Ferragut J., Carrascosa A., Potau N. Clin. Genet. 57:67-69(2000) [PubMed: 10733238] [Abstract] Cited for: VARIANTS IRAN TYPE A LEU-167 AND VAL-1055.
[100]	"Identification of novel C253Y missense and Y864X nonsense mutations in the insulin receptor gene in type A insulin-resistant patients." Osawa H., Nishimiya T., Ochi M., Niiya T., Onuma H., Kitamuro F., Kaino Y., Kida K., Makino H. Clin. Genet. 59:194-197(2001) [PubMed: 11260230] [Abstract] Cited for: VARIANT IRAN TYPE A TYR-280.
[101]	"An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events." Hamer I., Foti M., Emkey R., Cordier-Bussat M., Philippe J., De Meyts P., Maeder C., Kahn C.R., Carpentier J.-L. Diabetologia 45:657-667(2002) [PubMed: 12107746] [Abstract] Cited for: VARIANT IRAN TYPE A CYS-279.
[102]	"Genotype-phenotype correlation in inherited severe insulin resistance." Longo N., Wang Y., Smith S.A., Langley S.D., DiMeglio L.A., Giannella-Neto D. Hum. Mol. Genet. 11:1465-1475(2002) [PubMed: 12023989] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS LEPRCH PRO-113; VAL-119; ASN-308 DEL; THR-925 AND TRP-926, VARIANTS RMS THR-997; THR-1143; TRP-1158 AND TRP-1201.
[103]	"Deletion of V335 from the L2 domain of the insulin receptor results in a conformationally abnormal receptor that is unable to bind insulin and causes Donohue's syndrome in a human subject." George S., Johansen A., Soos M.A., Mortensen H., Gammeltoft S., Saudek V., Siddle K., Hansen L., O'Rahilly S. Endocrinology 144:631-637(2003) [PubMed: 12538626] [Abstract] Cited for: VARIANT LEPRCH VAL-362 DEL.
[104]	"Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance." Maassen J.A., Tobias E.S., Kayserilli H., Tukel T., Yuksel-Apak M., D'Haens E., Kleijer W.J., Fery F., van der Zon G.C.M. J. Clin. Endocrinol. Metab. 88:4251-4257(2003) [PubMed: 12970295] [Abstract] Cited for: VARIANT IRAN TYPE A HIS-279, VARIANTS LEPRCH GLN-120; LEU-350; ASP-458 AND TRP-1119, CHARACTERIZATION OF VARIANT IRAN TYPE A HIS-279, CHARACTERIZATION OF VARIANTS LEPRCH GLN-120 AND ASP-458.
[105]	"A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene." Hoejlund K., Hansen T., Lajer M., Henriksen J.E., Levin K., Lindholm J., Pedersen O., Bech-Nielsen H. Diabetes 53:1592-1598(2004) [PubMed: 15161766] [Abstract] Cited for: VARIANT HHF5 GLN-1201.
[106]	"Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome." Tuthill A., Semple R.K., Day R., Soos M.A., Sweeney E., Seymour P.J., Didi M., O'Rahilly S. Clin. Endocrinol. (Oxf.) 66:21-26(2007) [PubMed: 17201797] [Abstract] Cited for: VARIANTS RMS ARG-236 AND SER-386, CHARACTERIZATION OF VARIANTS RMS ARG-236 AND SER-386.
[107]	"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] ARG-228; ARG-695; SER-811; MET-1012; VAL-1065 AND ALA-1282.
+	Additional computationally mapped references.

Web resources

Wikipedia

Insulin receptor entry

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M10051 mRNA. Translation: AAA59174.1.
X02160 mRNA. Translation: CAA26096.1.
M32972 , M23100, M32823, M32824, M32825, M32826, M32827, M32828, M32829, M32830, M32831, M32832, M32833, M32834, M32835, M32836, M32837, M32838, M32839, M32840, M32841, M32842 Genomic DNA. Translation: AAA59452.1.
AC010311 Genomic DNA. No translation available.
AC010526 Genomic DNA. No translation available.
AC010606 Genomic DNA. No translation available.
AC125387 Genomic DNA. No translation available.
BC117172 mRNA. Translation: AAI17173.1.
J03466 Genomic DNA. Translation: AAA59175.1.
J05043 Genomic DNA. Translation: AAA59190.1.
M76592 Genomic DNA. Translation: AAC37604.1.
AB208861 mRNA. Translation: BAD92098.1.
M24555 mRNA. Translation: AAA59178.1.
M29929 Genomic DNA. Translation: AAA59176.1.
M29930 Genomic DNA. Translation: AAA59177.1.
M27197, M27195 Genomic DNA. Translation: AAA86791.1.

IPI

IPI00025803.
IPI00220325.

PIR

INHUR. A37348.

RefSeq

NP_000199.2. NM_000208.2.
NP_001073285.1. NM_001079817.1.

UniGene

Hs.465744.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GAG	X-ray	2.70	A	1005-1310	[»]
1I44	X-ray	2.40	A	1005-1310	[»]
1IR3	X-ray	1.90	A	1005-1310	[»]
1IRK	X-ray	2.10	A	1005-1310	[»]
1P14	X-ray	1.90	A	1005-1298	[»]
1RQQ	X-ray	2.60	A/B	1005-1310	[»]
2AUH	X-ray	3.20	A	1005-1310	[»]
2B4S	X-ray	2.30	B/D	1005-1310	[»]
2DTG	X-ray	3.80	E	28-943	[»]
2HR7	X-ray	2.32	A/B	28-512	[»]
2Z8C	X-ray	3.25	A	1009-1310	[»]
3BU3	X-ray	1.65	A	1005-1310	[»]
3BU5	X-ray	2.10	A	1005-1310	[»]
3BU6	X-ray	1.95	A	1005-1310	[»]
3EKK	X-ray	2.10	A	1005-1310	[»]
3EKN	X-ray	2.20	A	1005-1310	[»]
3ETA	X-ray	2.60	A/B	1017-1322	[»]
3LOH	X-ray	3.80	E	28-956	[»]

ProteinModelPortal

P06213.

SMR

P06213. Positions 31-948, 1009-1310.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-480N.
DIP-6025N.

IntAct

P06213. 22 interactions.

MINT

MINT-1516246.

STRING

P06213.

PTM databases

PhosphoSite

P06213.

Polymorphism databases

DMDM

308153655.

Proteomic databases

PRIDE

P06213.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302850; ENSP00000303830; ENSG00000171105.

GeneID

3643.

KEGG

hsa:3643.

UCSC

uc002mgd.1. human.

Organism-specific databases

CTD

3643.

GeneCards

GC19M007067.

H-InvDB

HIX0040111.

HGNC

HGNC:6091. INSR.

HPA

CAB013113.

MIM

125853. phenotype.
147670. gene.
246200. phenotype.
262190. phenotype.
609968. phenotype.
610549. phenotype.

neXtProt

NX_P06213.

Orphanet

657. Congenital isolated hyperinsulinism.
263458. Hyperinsulinism due to INSR deficiency.
2297. Insulin-resistance syndrome type A.
508. Leprechaunism.
769. Rabson-Mendenhall syndrome.

PharmGKB

PA202.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17961.

HOGENOM

HBG316019.

HOVERGEN

HBG006134.

InParanoid

P06213.

OMA

THYLVYW.

PhylomeDB

P06213.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

insulin_pathway. Insulin Pathway.
insulin_glucose_pathway. Insulin-mediated glucose transport.
mtor_4pathway. mTOR signaling pathway.
ptp1bpathway. Signaling events mediated by PTP1B.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P06213.

Bgee

P06213.

CleanEx

HS_INSR.

Genevestigator

P06213.

GermOnline

ENSG00000171105. Homo sapiens.

Family and domain databases

InterPro

IPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
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.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]

KO

K04527.

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. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 2 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

DrugBank

DB00047. Insulin Glargine recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.

SOURCE

Search...

Entry information

Entry name

INSR_HUMAN

Accession

Primary (citable) accession number: P06213
Secondary accession number(s): Q17RW0 , Q59H98, Q9UCB7, Q9UCB8, Q9UCB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	October 5, 2010
Last modified:	January 25, 2012
This is version 176 of the entry and version 4 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.