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P06213 (INSR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 204. Feed History...

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

Names and origin

Protein namesRecommended name:
Insulin receptor

Short name=IR
EC=2.7.10.1
Alternative name(s):
CD_antigen=CD220
Gene names
Name:INSR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1382 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor tyrosine kinase which mediates 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.40 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.46 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.40 Ref.44 Ref.46

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.38 Ref.55 Ref.56 Ref.57 Ref.63 Ref.65 Ref.66 Ref.67

Enzyme regulation

Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate 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.38 Ref.39 Ref.41

Subunit structure

Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains carry the insulin-binding regions, 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. 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.11 Ref.25 Ref.26 Ref.27 Ref.29 Ref.30 Ref.31 Ref.34 Ref.36 Ref.37 Ref.39 Ref.41 Ref.43 Ref.44 Ref.59 Ref.63

Subcellular location

Cell 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

Domain

The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2. Ref.50 Ref.61 Ref.69

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.62 Ref.69

Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-999 is required for binding to IRS1, SHC1 and STAT5B. Dephosphorylated by PTPRE at Tyr-999, Tyr-1185, Tyr-1189 and Tyr-1190. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling. Ref.15 Ref.17 Ref.22 Ref.31 Ref.35 Ref.42 Ref.45 Ref.55 Ref.57 Ref.58 Ref.59 Ref.60 Ref.63 Ref.64

Involvement in disease

Rabson-Mendenhall syndrome (RMS) [MIM:262190]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.75 Ref.76 Ref.96 Ref.110 Ref.114 Ref.118

Leprechaunism (LEPRCH) [MIM:246200]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.71 Ref.72 Ref.76 Ref.81 Ref.84 Ref.93 Ref.94 Ref.98 Ref.100 Ref.102 Ref.104 Ref.107 Ref.108 Ref.109 Ref.114 Ref.115 Ref.116

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.82 Ref.85 Ref.101

Familial hyperinsulinemic hypoglycemia 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.117

Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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 processCarbohydrate metabolism
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDiabetes mellitus
Disease mutation
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 9092559. Source: BHF-UCL

activation of MAPK activity

Inferred from mutant phenotype PubMed 17001305. Source: BHF-UCL

activation of protein kinase B activity

Inferred from direct assay PubMed 7556070. Source: BHF-UCL

activation of protein kinase activity

Inferred from mutant phenotype PubMed 9819385. Source: BHF-UCL

carbohydrate metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from direct assay PubMed 8440175. Source: BHF-UCL

exocrine pancreas development

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from mutant phenotype PubMed 7693131. Source: BHF-UCL

heart morphogenesis

Inferred from mutant phenotype PubMed 7693131. Source: BHF-UCL

insulin receptor signaling pathway

Inferred from direct assay PubMed 8440175. Source: UniProtKB

male sex determination

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 8496180. Source: BHF-UCL

positive regulation of DNA replication

Inferred from mutant phenotype Ref.40. Source: BHF-UCL

positive regulation of MAPK cascade

Inferred from mutant phenotype PubMed 11500939. Source: BHF-UCL

positive regulation of cell migration

Inferred from mutant phenotype Ref.40. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from direct assay PubMed 17925406. Source: BHF-UCL

positive regulation of developmental growth

Inferred from mutant phenotype PubMed 7693131. Source: BHF-UCL

positive regulation of glucose import

Inferred from direct assay PubMed 3518947. Source: BHF-UCL

positive regulation of glycogen biosynthetic process

Inferred from direct assay PubMed 17925406. Source: BHF-UCL

positive regulation of glycolytic process

Inferred from mutant phenotype PubMed 7693131. Source: BHF-UCL

positive regulation of mitosis

Inferred from mutant phenotype PubMed 11500939. Source: BHF-UCL

positive regulation of nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 10747347. Source: BHF-UCL

positive regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 11500939. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 7556070. Source: BHF-UCL

positive regulation of respiratory burst

Inferred from direct assay PubMed 9092559. Source: BHF-UCL

protein autophosphorylation

Inferred from mutant phenotype Ref.27. Source: UniProtKB

protein heterotetramerization

Inferred from direct assay PubMed 1898103. Source: UniProtKB

regulation of embryonic development

Inferred from mutant phenotype PubMed 7693131. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 12881524. Source: BHF-UCL

signal transduction by phosphorylation

Inferred from direct assay PubMed 6849137. Source: GOC

transformation of host cell by virus

Inferred from mutant phenotype PubMed 17001305. Source: BHF-UCL

   Cellular_componentcaveola

Inferred from direct assay PubMed 15182363. Source: BHF-UCL

endosome membrane

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

insulin receptor complex

Inferred from mutant phenotype PubMed 15069075. Source: BHF-UCL

integral component of plasma membrane

Inferred from direct assay PubMed 9092559. Source: BHF-UCL

membrane

Inferred from direct assay Ref.24. Source: BHF-UCL

plasma membrane

Inferred by curator PubMed 6849137. Source: BHF-UCL

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from direct assay PubMed 6849137. Source: BHF-UCL

GTP binding

Inferred from direct assay PubMed 9092559. 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 PubMed 8440175. Source: UniProtKB

insulin receptor substrate binding

Inferred from physical interaction Ref.27Ref.26. Source: UniProtKB

insulin-activated receptor activity

Inferred from direct assay PubMed 8440175. 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.40. Source: BHF-UCL

insulin-like growth factor receptor binding

Inferred from direct assay Ref.24. Source: BHF-UCL

phosphatidylinositol 3-kinase binding

Inferred from physical interaction Ref.27Ref.25. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 7493946. Source: BHF-UCL

protein tyrosine kinase activity

Inferred from mutant phenotype Ref.27. Source: UniProtKB

receptor signaling protein tyrosine kinase activity

Inferred from direct assay PubMed 6849137. 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Ref.2 Ref.11 Ref.12
Chain28 – 758731Insulin receptor subunit alpha
PRO_0000016687
Chain763 – 1382620Insulin receptor subunit beta
PRO_0000016689

Regions

Topological domain28 – 758731Extracellular Probable
Topological domain763 – 956194Extracellular Probable
Transmembrane957 – 97923Helical; Potential
Topological domain980 – 1382403Cytoplasmic Probable
Domain624 – 726103Fibronectin type-III 1
Domain757 – 84286Fibronectin type-III 2
Domain853 – 94795Fibronectin type-III 3
Domain1023 – 1298276Protein kinase
Nucleotide binding1104 – 11107ATP
Nucleotide binding1163 – 11642ATP
Region733 – 7419Insulin-binding
Region9991Important for interaction with IRS1, SHC1 and STAT5B
Region1361 – 13644PIK3R1-binding
Compositional bias28 – 174147Leu-rich
Compositional bias182 – 339158Cys-rich

Sites

Active site11591Proton donor/acceptor Ref.55
Binding site10331ATP
Binding site10571ATP
Binding site11771ATP
Site661Insulin-binding Probable

Amino acid modifications

Modified residue4001Phosphoserine Ref.49
Modified residue4011Phosphotyrosine Ref.49
Modified residue4071Phosphoserine Ref.49
Modified residue9921Phosphotyrosine; by autocatalysis Probable
Modified residue9991Phosphotyrosine; by autocatalysis Probable
Modified residue10111Phosphotyrosine; by autocatalysis Probable
Modified residue11851Phosphotyrosine; by autocatalysis Ref.17 Ref.55 Ref.58 Ref.59 Ref.60 Ref.63 Ref.64
Modified residue11891Phosphotyrosine; by autocatalysis Ref.17 Ref.55 Ref.58 Ref.59 Ref.60 Ref.63 Ref.64
Modified residue11901Phosphotyrosine; by autocatalysis Ref.17 Ref.55 Ref.58 Ref.59 Ref.60 Ref.63 Ref.64
Modified residue13551Phosphotyrosine; by autocatalysis Probable
Modified residue13611Phosphotyrosine; by autocatalysis Probable
Glycosylation431N-linked (GlcNAc...) Ref.2 Ref.62 Ref.69
Glycosylation521N-linked (GlcNAc...) Ref.62 Ref.69
Glycosylation1051N-linked (GlcNAc...) Potential
Glycosylation1381N-linked (GlcNAc...) Ref.62 Ref.69
Glycosylation2421N-linked (GlcNAc...) Ref.51 Ref.62 Ref.69
Glycosylation2821N-linked (GlcNAc...) Ref.62 Ref.69
Glycosylation3221N-linked (GlcNAc...) Potential
Glycosylation3641N-linked (GlcNAc...) Ref.62
Glycosylation4241N-linked (GlcNAc...) Ref.62
Glycosylation4451N-linked (GlcNAc...) Ref.53 Ref.62
Glycosylation5411N-linked (GlcNAc...) Ref.23 Ref.51
Glycosylation6331N-linked (GlcNAc...) Potential
Glycosylation6511N-linked (GlcNAc...) Potential
Glycosylation6981N-linked (GlcNAc...) Potential
Glycosylation7691N-linked (GlcNAc...) Ref.2
Glycosylation7821N-linked (GlcNAc...) Potential
Glycosylation9201N-linked (GlcNAc...) Ref.53
Glycosylation9331N-linked (GlcNAc...) Potential
Disulfide bond35 ↔ 53 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond153 ↔ 182 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond186 ↔ 209 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond196 ↔ 215 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond219 ↔ 228 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond223 ↔ 234 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond235 ↔ 243 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond239 ↔ 252 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond255 ↔ 264 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond268 ↔ 280 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond286 ↔ 311 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond293 ↔ 301 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond315 ↔ 328 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond331 ↔ 335 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond339 ↔ 360 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond462 ↔ 495 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond551Interchain Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond674 ↔ 899 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69
Disulfide bond825 ↔ 834 Ref.23 Ref.61 Ref.62 Ref.68 Ref.69

Natural variations

Alternative sequence745 – 75612Missing in isoform Short.
VSP_002898
Natural variant21A → 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 variant421N → K in RMS; impairs transport to the plasma membrane and reduces the affinity to bind insulin. Ref.75 Ref.76
VAR_004079
Natural variant551V → A in LEPRCH; Verona-1. Ref.81
VAR_004080
Natural variant581G → R in LEPRCH; Helmond; inhibits processing and transport. Ref.84
Corresponds to variant rs52836744 [ dbSNP | Ensembl ].
VAR_004081
Natural variant861D → G in IRAN type A. Ref.106
VAR_015907
Natural variant891L → P in IRAN type A. Ref.106
VAR_015908
Natural variant1131R → P in LEPRCH; Atlanta-1; abolishes insulin binding. Ref.94 Ref.114
VAR_004082
Natural variant1191A → V in LEPRCH; markedly impairs insulin binding. Ref.114
VAR_015909
Natural variant1201L → Q in LEPRCH; inhibits receptor processing. Ref.116
VAR_031518
Natural variant1461I → M in LEPRCH; mild. Ref.93 Ref.100
VAR_015539
Natural variant1671V → L in IRAN type A. Ref.111
VAR_015910
Natural variant1711Y → H. Ref.1
Corresponds to variant rs1051692 [ dbSNP | Ensembl ].
VAR_058396
Natural variant2201P → L in Ins resistance; severe. Ref.90
VAR_004083
Natural variant2281C → R in a gastric adenocarcinoma sample; somatic mutation. Ref.119
VAR_041429
Natural variant2361H → R in LEPRCH; Winnipeg; in one patient with in RMS heterozygous compound with S-386; may impair receptor processing. Ref.76 Ref.118
VAR_004084
Natural variant2601L → P in LEPRCH; Geldeimalsen. Ref.72
VAR_004085
Natural variant2791R → C in IRAN type A; inhibits receptor internalization. Ref.113
VAR_015540
Natural variant2791R → H in IRAN type A; interferes with receptor processing. Ref.116
VAR_031519
Natural variant2801C → Y in IRAN type A. Ref.112
VAR_015911
Natural variant3011C → Y in LEPRCH. Ref.109
VAR_015912
Natural variant3081Missing in LEPRCH; abolishes insulin binding. Ref.102 Ref.104 Ref.114
VAR_015913
Natural variant3501S → L in RMS and LEPRCH. Ref.96 Ref.116
VAR_015914
Natural variant3621Missing in LEPRCH. Ref.115
VAR_015541
Natural variant3861G → S in RMS; may impair receptor processing. Ref.118
VAR_031520
Natural variant3931G → R in LEPRCH; Verona-1. Ref.81
VAR_004086
Natural variant4091F → V in IRAN type A. Ref.92
VAR_004087
Natural variant4391W → S in LEPRCH; impairs transport of the receptor to the cell surface. Ref.98
VAR_015542
Natural variant4481I → T. Ref.1
Corresponds to variant rs1051691 [ dbSNP | Ensembl ].
VAR_015915
Natural variant4581N → D in LEPRCH; partially inhibits receptor processing and autophosphorylation; strongly impairs ERK phosphorylation; induces wild-type levels of IRS-1 phosphorylation. Ref.116
VAR_031521
Natural variant4871K → E in LEPRCH; ARK-1. Ref.71
Corresponds to variant rs28933083 [ dbSNP | Ensembl ].
VAR_004088
Natural variant4891N → S in IRAN type A. Ref.76
Corresponds to variant rs28933085 [ dbSNP | Ensembl ].
VAR_004089
Natural variant4921Q → K. Ref.1
Corresponds to variant rs1131851 [ dbSNP | Ensembl ].
VAR_015916
Natural variant6951Q → R. Ref.119
Corresponds to variant rs55906835 [ dbSNP | Ensembl ].
VAR_041430
Natural variant7621R → S in IRAN type A. Ref.70
VAR_004090
Natural variant8111G → S. Ref.119
Corresponds to variant rs35045353 [ dbSNP | Ensembl ].
VAR_041431
Natural variant8301P → L.
Corresponds to variant rs2162771 [ dbSNP | Ensembl ].
VAR_055986
Natural variant8581T → A in NIDDM. Ref.101
Corresponds to variant rs182552223 [ dbSNP | Ensembl ].
VAR_015917
Natural variant9251I → T in LEPRCH; abolishes insulin binding. Ref.114
VAR_015918
Natural variant9261R → W in LEPRCH; markedly impairs insulin binding. Ref.114
VAR_015919
Natural variant9371T → M in LEPRCH; impaired receptor processing. Ref.107
VAR_015920
Natural variant9971P → T in RMS; reduces insulin binding. Ref.114
VAR_015921
Natural variant10121V → M Rare polymorphism. Ref.86 Ref.88 Ref.96 Ref.105 Ref.119
Corresponds to variant rs1799816 [ dbSNP | Ensembl ].
VAR_004091
Natural variant10201R → Q in IRAN type A. Ref.79
VAR_004092
Natural variant10231I → F. Ref.103
VAR_015922
Natural variant10351G → V in IRAN type A. Ref.73
VAR_004093
Natural variant10551A → V in IRAN type A. Ref.111
VAR_015923
Natural variant10651L → V. Ref.119
Corresponds to variant rs56395521 [ dbSNP | Ensembl ].
VAR_041432
Natural variant10751A → D in IRAN type A. Ref.87
VAR_004094
Natural variant10951K → E in a NIDDM subject. Ref.78
VAR_015924
Natural variant11191R → W in LEPRCH. Ref.108 Ref.116
VAR_015925
Natural variant11431I → T in RMS; reduces insulin binding. Ref.110 Ref.114
VAR_015926
Natural variant11581R → Q in NIDDM. Ref.85
VAR_015927
Natural variant11581R → W in RMS; abolishes insulin binding. Ref.110 Ref.114
VAR_015928
Natural variant11611A → T in IRAN type A. Ref.74
Corresponds to variant rs28933084 [ dbSNP | Ensembl ].
VAR_004095
Natural variant11621A → E in IRAN type A; impairs proteolytic processing. Ref.91
VAR_004096
Natural variant11801M → I in a patient with insulin resistance. Ref.80
VAR_004097
Natural variant11911R → Q in NIDDM. Ref.82
VAR_004098
Natural variant12011R → Q in HHF5 and IRAN type A; interferes with kinase activation by insulin. Ref.95 Ref.97 Ref.117
Corresponds to variant rs28933086 [ dbSNP | Ensembl ].
VAR_015929
Natural variant12011R → W in LEPRCH and RMS; reduces insulin binding possibly due to reduced receptor levels on the cell surface. Ref.109 Ref.114
VAR_015930
Natural variant12051P → L in IRAN type A; moderate. Ref.83 Ref.96
VAR_004099
Natural variant12061E → D in IRAN type A; accelerates degradation of the protein and impairs kinase activity. Ref.99
VAR_015931
Natural variant12061E → K in LEPRCH. Ref.108
VAR_015932
Natural variant12201W → L in IRAN type A; accelerates degradation of the protein and impairs kinase activity. Ref.89 Ref.99
Corresponds to variant rs52800171 [ dbSNP | Ensembl ].
VAR_004100
Natural variant12271W → S in IRAN type A. Ref.77
VAR_004101
Natural variant12821T → A. Ref.119
Corresponds to variant rs55875349 [ dbSNP | Ensembl ].
VAR_041433
Natural variant13611Y → C. Ref.101
Corresponds to variant rs13306449 [ dbSNP | Ensembl ].
VAR_015933
Natural variant13781R → Q in IRAN type A. Ref.96
Corresponds to variant rs52826008 [ dbSNP | Ensembl ].
VAR_015934

Experimental info

Mutagenesis9911L → A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. Ref.26
Mutagenesis9921Y → A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. Ref.26
Mutagenesis996 – 9972NP → AA: Abolishes interaction with IRS1. Severely disrupts, but does not abolish interaction with SHC1. Ref.26 Ref.27
Mutagenesis9961N → A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. Ref.26 Ref.27
Mutagenesis9971P → A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. Ref.26 Ref.27
Mutagenesis9981E → A: Does not affect interaction with IRS1, SHC1 or PIK3R1. Ref.27
Mutagenesis9991Y → E: Abolishes interaction with IRS1 and SHC1. Ref.21 Ref.26 Ref.27 Ref.29
Mutagenesis9991Y → 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
Mutagenesis10001L → A or R: Severely reduces interaction with SHC1. Has no effect on interaction with IRS1. Ref.26
Mutagenesis10021A → D: Reduces interaction with IRS1 but has no effect on interaction with SHC1. Ref.26
Mutagenesis10111Y → A: Increases kinase activity. Ref.57
Mutagenesis10571K → A: Abolishes the kinase activity and abolishes interaction with IRS1, SHC1, GRB7 and PIK3R1. Ref.20 Ref.27 Ref.36
Mutagenesis10571K → M or R: Abolishes the kinase activity. Ref.20 Ref.27 Ref.36
Mutagenesis11591D → N: Loss of kinase activity. Ref.38
Mutagenesis11631R → Q: Loss of kinase activity. Ref.38
Mutagenesis11891Y → F: Reduced interaction with GRB7. Ref.36
Mutagenesis11901Y → F: Strongly reduced interaction with GRB7. Ref.36
Sequence conflict6011D → N AA sequence Ref.19
Sequence conflict8301P → E AA sequence Ref.19
Sequence conflict12781K → N in CAA26096. Ref.2

Secondary structure

.............................................................................................................................................................. 1382
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long (HIR-B) [UniParc].

Last modified October 5, 2010. Version 4.
Checksum: 709A955660739066

FASTA1,382156,333
        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 

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Isoform Short (HIR-A) [UniParc].

Checksum: A396F39279C2764D
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FASTA1,370155,146

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [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] (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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 927-956; 981-1019; 1182-1194 AND 1352-1369, PHOSPHORYLATION AT TYR-999; TYR-1355 AND TYR-1361.
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ENPP1, ENZYME REGULATION.
[35]"Identification of tyrosine phosphatases that dephosphorylate the insulin receptor. A brute force approach based on 'substrate-trapping' mutants."
Waelchli S., Curchod M.L., Gobert R.P., Arkinstall S., Hooft van Huijsduijnen R.
J. Biol. Chem. 275:9792-9796(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN1 AND PTPN2.
[36]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB7, MUTAGENESIS OF LYS-1057; TYR-1189 AND TYR-1190.
[37]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SORBS1.
[38]"Multiple activation loop conformations and their regulatory properties in the insulin receptor's kinase domain."
Ablooglu A.J., Frankel M., Rusinova E., Ross J.B., Kohanski R.A.
J. Biol. Chem. 276:46933-46940(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-1159 AND ARG-1163, ENZYME REGULATION.
[39]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB14, ENZYME REGULATION.
[40]"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 IGF1R.
[41]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB10, ENZYME REGULATION.
[42]"Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP."
Galic S., Klingler-Hoffmann M., Fodero-Tavoletti M.T., Puryer M.A., Meng T.C., Tonks N.K., Tiganis T.
Mol. Cell. Biol. 23:2096-2108(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN2.
[43]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SOCS7.
[44]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PDPK1, INTERACTION WITH PDPK1.
[45]"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] [Europe PMC] [Abstract]
Cited for: DEPHOSPHORYLATION BY PTPRE.
[46]"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 IGF1R.
[47]"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] [Europe PMC] [Abstract]
Cited for: REVIEW ON SIGNALING PATHWAYS.
[48]"Regulation of insulin receptor function."
Youngren J.F.
Cell. Mol. Life Sci. 64:873-891(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON REGULATION OF INSR FUNCTION.
[49]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400; TYR-401 AND SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[50]"A thermodynamic study of ligand binding to the first three domains of the human insulin receptor: relationship between the receptor alpha-chain C-terminal peptide and the site 1 insulin mimetic peptides."
Menting J.G., Ward C.W., Margetts M.B., Lawrence M.C.
Biochemistry 48:5492-5500(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, INSULIN-BINDING SITE.
[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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242 AND ASN-541.
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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-445 AND ASN-920.
Tissue: Leukemic T-cell.
[54]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1005-1310.
[55]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP ANALOG AND IRS1 PEPTIDE, CATALYTIC ACTIVITY, ACTIVE SITE, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
[56]"Crystallographic and solution studies of an activation loop mutant of the insulin receptor tyrosine kinase: insights into kinase mechanism."
Till J.H., Ablooglu A.J., Frankel M., Bishop S.M., Kohanski R.A., Hubbard S.R.
J. Biol. Chem. 276:10049-10055(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP ANALOG, CATALYTIC ACTIVITY.
[57]"Structural and biochemical evidence for an autoinhibitory role for tyrosine 984 in the juxtamembrane region of the insulin receptor."
Li S., Covino N.D., Stein E.G., Till J.H., Hubbard S.R.
J. Biol. Chem. 278:26007-26014(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1005-1298 OF MUTANT ASN-1159, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1011.
[58]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP ANALOG AND SH2B2, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
[59]"Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14."
Depetris R.S., Hu J., Gimpelevich I., Holt L.J., Daly R.J., Hubbard S.R.
Mol. Cell 20:325-333(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH GRB14, INTERACTION WITH GRB14, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
[60]"Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase."
Li S., Depetris R.S., Barford D., Chernoff J., Hubbard S.R.
Structure 13:1643-1651(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH PTPN1, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
[61]"Structure of the insulin receptor ectodomain reveals a folded-over conformation."
McKern N.M., Lawrence M.C., Streltsov V.A., Lou M.Z., Adams T.E., Lovrecz G.O., Elleman T.C., Richards K.M., Bentley J.D., Pilling P.A., Hoyne P.A., Cartledge K.A., Pham T.M., Lewis J.L., Sankovich S.E., Stoichevska V., Da Silva E., Robinson C.P. expand/collapse author list , Frenkel M.J., Sparrow L.G., Fernley R.T., Epa V.C., Ward C.W.
Nature 443:218-221(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 28-943 IN COMPLEX WITH INSULIN ANALOG, DOMAIN, DISULFIDE BONDS.
[62]"The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity."
Lou M., Garrett T.P., McKern N.M., Hoyne P.A., Epa V.C., Bentley J.D., Lovrecz G.O., Cosgrove L.J., Frenkel M.J., Ward C.W.
Proc. Natl. Acad. Sci. U.S.A. 103:12429-12434(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF 28-512, GLYCOSYLATION AT ASN-43; ASN-52; ASN-138; ASN-242; ASN-282; ASN-364; ASN-424 AND ASN-445, DISULFIDE BONDS.
[63]"Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2."
Wu J., Tseng Y.D., Xu C.F., Neubert T.A., White M.F., Hubbard S.R.
Nat. Struct. Mol. Biol. 15:251-258(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP AND IRS2, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190, INTERACTION WITH IRS2.
[64]"Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors."
Katayama N., Orita M., Yamaguchi T., Hisamichi H., Kuromitsu S., Kurihara H., Sakashita H., Matsumoto Y., Fujita S., Niimi T.
Proteins 73:795-801(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 1009-1310 IN COMPLEX WITH INHIBITORY PEPTIDE, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
[65]"Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity."
Chamberlain S.D., Redman A.M., Wilson J.W., Deanda F., Shotwell J.B., Gerding R., Lei H., Yang B., Stevens K.L., Hassell A.M., Shewchuk L.M., Leesnitzer M.A., Smith J.L., Sabbatini P., Atkins C., Groy A., Rowand J.L., Kumar R. expand/collapse author list , Mook R.A. Jr., Moorthy G., Patnaik S.
Bioorg. Med. Chem. Lett. 19:360-364(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH SYNTHETIC INHIBITOR, CATALYTIC ACTIVITY.
[66]"Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase."
Chamberlain S.D., Wilson J.W., Deanda F., Patnaik S., Redman A.M., Yang B., Shewchuk L., Sabbatini P., Leesnitzer M.A., Groy A., Atkins C., Gerding R., Hassell A.M., Lei H., Mook R.A. Jr., Moorthy G., Rowand J.L., Stevens K.L., Kumar R., Shotwell J.B.
Bioorg. Med. Chem. Lett. 19:469-473(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH SYNTHETIC INHIBITOR, CATALYTIC ACTIVITY.
[67]"Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase."
Patnaik S., Stevens K.L., Gerding R., Deanda F., Shotwell J.B., Tang J., Hamajima T., Nakamura H., Leesnitzer M.A., Hassell A.M., Shewchuck L.M., Kumar R., Lei H., Chamberlain S.D.
Bioorg. Med. Chem. Lett. 19:3136-3140(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1017-1322 IN COMPLEX WITH SYNTHETIC INHIBITOR, CATALYTIC ACTIVITY.
[68]"Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists."
Smith B.J., Huang K., Kong G., Chan S.J., Nakagawa S., Menting J.G., Hu S.Q., Whittaker J., Steiner D.F., Katsoyannis P.G., Ward C.W., Weiss M.A., Lawrence M.C.
Proc. Natl. Acad. Sci. U.S.A. 107:6771-6776(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) OF 28-956, INSULIN-BINDING REGION, DISULFIDE BONDS.
[69]"How insulin engages its primary binding site on the insulin receptor."
Menting J.G., Whittaker J., Margetts M.B., Whittaker L.J., Kong G.K., Smith B.J., Watson C.J., Zakova L., Kletvikova E., Jiracek J., Chan S.J., Steiner D.F., Dodson G.G., Brzozowski A.M., Weiss M.A., Ward C.W., Lawrence M.C.
Nature 493:241-245(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.9 ANGSTROMS) OF 28-620 IN COMPLEX WITH INSULIN, DOMAIN, GLYCOSYLATION AT ASN-43; ASN-52; ASN-138; ASN-242 AND ASN-282, DISULFIDE BONDS.
[70]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A SER-762.
[71]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH GLU-487.
[72]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH PRO-260.
[73]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A VAL-1035.
[74]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A THR-1161.
[75]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT RMS LYS-42.
[76]"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] [Europe PMC] [Abstract]
Cited for: VARIANT RMS LYS-42, VARIANT LEPRCH ARG-236, VARIANT IRAN TYPE A SER-489.
[77]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A SER-1227.
[78]"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] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-1095.
[79]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A GLN-1020.
[80]"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] [Europe PMC] [Abstract]
Cited for: VARIANT INS RESISTANCE ILE-1180.
[81]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS LEPRCH ALA-55 AND ARG-393.
[82]"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] [Europe PMC] [Abstract]
Cited for: VARIANT NIDDM GLN-1191.
[83]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A LEU-1205.
[84]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH ARG-58.
[85]"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] [Europe PMC] [Abstract]
Cited for: VARIANT NIDDM GLN-1158.
[86]"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] [Europe PMC] [Abstract]
Cited for: VARIANT MET-1012.
[87]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A ASP-1075.
[88]"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] [Europe PMC] [Abstract]
Cited for: VARIANT MET-1012.
[89]"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] [Europe PMC] [Abstract]
Cited for: VARIANT INS RESISTANCE LEU-1220.
[90]"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] [Europe PMC] [Abstract]
Cited for: VARIANT INS RESISTANCE LEU-220.
[91]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT IRAN TYPE A GLU-1162.
[92]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A VAL-409.
[93]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH MET-146.
[94]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH PRO-113.
[95]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A GLN-1201.
[96]"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] [Europe PMC] [Abstract]
Cited for: VARIANT RMS SYNDROME LEU-350, VARIANTS IRAN TYPE A LEU-1205 AND GLN-1378, VARIANT MET-1012.
[97]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT IRAN TYPE A GLN-1201.
[98]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH SER-439.
[99]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS IRAN TYPE A ASP-1206 AND LEU-1220.
[100]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH MET-146.
[101]"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] [Europe PMC] [Abstract]
Cited for: VARIANT NIDDM ALA-858, VARIANT CYS-1361.
[102]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH ASN-308 DEL.
[103]"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] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-1023.
[104]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH ASN-308 DEL.
[105]"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] [Europe PMC] [Abstract]
Cited for: VARIANT MET-1012.
[106]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS IRAN TYPE A GLY-86 AND PRO-89.
[107]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LEPRCH MET-937.
[108]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS LEPRCH TRP-1119 AND LYS-1206.
[109]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS LEPRCH TYR-301 AND TRP-1201.
[110]"Progressive decline in insulin levels in Rabson-Mendenhall syndrome."
Longo N., Wang Y., Pasquali M.
J. Clin. Endocrinol. Metab. 84:2623-2629(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RMS THR-1143 AND TRP-1158.
[111]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS IRAN TYPE A LEU-167 AND VAL-1055.
[112]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A TYR-280.
[113]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IRAN TYPE A CYS-279.
[114]"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] [Europe PMC] [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.
[115]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEPRCH VAL-362 DEL.
[116]"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] [Europe PMC] [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.
[117]"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] [Europe PMC] [Abstract]
Cited for: VARIANT HHF5 GLN-1201.
[118]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS RMS ARG-236 AND SER-386, CHARACTERIZATION OF VARIANTS RMS ARG-236 AND SER-386.
[119]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-228; ARG-695; SER-811; MET-1012; VAL-1065 AND ALA-1282.
+Additional computationally mapped references.

Web resources

Wikipedia

Insulin receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M10051 mRNA. Translation: AAA59174.1.
X02160 mRNA. Translation: CAA26096.1.
M32972 expand/collapse EMBL AC list , 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.
CCDSCCDS12176.1. [P06213-1]
CCDS42487.1. [P06213-2]
PIRINHUR. A37348.
RefSeqNP_000199.2. NM_000208.2. [P06213-1]
NP_001073285.1. NM_001079817.1. [P06213-2]
UniGeneHs.465744.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GAGX-ray2.70A1005-1310[»]
1I44X-ray2.40A1005-1310[»]
1IR3X-ray1.90A1005-1310[»]
1IRKX-ray2.10A1005-1310[»]
1P14X-ray1.90A1005-1310[»]
1RQQX-ray2.60A/B1005-1310[»]
2AUHX-ray3.20A1005-1310[»]
2B4SX-ray2.30B/D1005-1310[»]
2DTGX-ray3.80E28-955[»]
2HR7X-ray2.32A/B28-512[»]
2MFRNMR-A940-988[»]
2Z8CX-ray3.25A1008-1310[»]
3BU3X-ray1.65A1005-1310[»]
3BU5X-ray2.10A1005-1310[»]
3BU6X-ray1.95A1005-1310[»]
3EKKX-ray2.10A1005-1310[»]
3EKNX-ray2.20A1005-1310[»]
3ETAX-ray2.60A/B1017-1322[»]
3LOHX-ray3.80E28-956[»]
3W11X-ray3.90E28-337[»]
F731-744[»]
3W12X-ray4.30E28-337[»]
F731-744[»]
3W13X-ray4.30E28-337[»]
F724-744[»]
3W14X-ray4.40E/F28-746[»]
4IBMX-ray1.80A/B1005-1310[»]
ProteinModelPortalP06213.
SMRP06213. Positions 31-988, 1009-1339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109854. 58 interactions.
DIPDIP-480N.
IntActP06213. 42 interactions.
MINTMINT-1516246.
STRING9606.ENSP00000303830.

Chemistry

BindingDBP06213.
ChEMBLCHEMBL1981.
DrugBankDB00047. Insulin Glargine recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.
GuidetoPHARMACOLOGY1800.

PTM databases

PhosphoSiteP06213.

Polymorphism databases

DMDM308153655.

Proteomic databases

MaxQBP06213.
PaxDbP06213.
PRIDEP06213.

Protocols and materials databases

DNASU3643.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302850; ENSP00000303830; ENSG00000171105. [P06213-1]
ENST00000341500; ENSP00000342838; ENSG00000171105. [P06213-2]
GeneID3643.
KEGGhsa:3643.
UCSCuc002mgd.1. human. [P06213-1]
uc002mge.1. human. [P06213-2]

Organism-specific databases

CTD3643.
GeneCardsGC19M007112.
H-InvDBHIX0040111.
HGNCHGNC:6091. INSR.
HPAHPA036302.
MIM125853. phenotype.
147670. gene.
246200. phenotype.
262190. phenotype.
609968. phenotype.
610549. phenotype.
neXtProtNX_P06213.
Orphanet263458. Hyperinsulinism due to INSR deficiency.
2297. Insulin-resistance syndrome type A.
508. Leprechaunism.
769. Rabson-Mendenhall syndrome.
PharmGKBPA202.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000038045.
HOVERGENHBG006134.
InParanoidP06213.
KOK04527.
OMACPERVTD.
OrthoDBEOG73RB9N.
PhylomeDBP06213.
TreeFamTF351636.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SABIO-RKP06213.
SignaLinkP06213.

Gene expression databases

ArrayExpressP06213.
BgeeP06213.
CleanExHS_INSR.
GenevestigatorP06213.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
3.80.20.20. 2 hits.
InterProIPR000494. EGF_rcpt_L.
IPR003961. Fibronectin_type3.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016246. Tyr_kinase_insulin-like_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamPF00041. fn3. 1 hit.
PF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFPIRSF000620. Insulin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 3 hits.
SM00261. FU. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS50853. FN3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSINSR. human.
EvolutionaryTraceP06213.
GeneWikiInsulin_receptor.
GenomeRNAi3643.
NextBio14259.
PROP06213.
SOURCESearch...

Entry information

Entry nameINSR_HUMAN
AccessionPrimary (citable) accession number: P06213
Secondary accession number(s): Q17RW0 expand/collapse secondary AC list , Q59H98, Q9UCB7, Q9UCB8, Q9UCB9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 5, 2010
Last modified: July 9, 2014
This is version 204 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human cell differentiation molecules

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