UniProtKB - P06213 (INSR_HUMAN)
Insulin receptor
INSR
Functioni
Catalytic activityi
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]PROSITE-ProRule annotation8 PublicationsEC:2.7.10.1PROSITE-ProRule annotation8 Publications
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 66 | Insulin-bindingCurated | 1 | |
Binding sitei | 1033 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Binding sitei | 1057 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Active sitei | 1159 | Proton donor/acceptor1 Publication | 1 | |
Binding sitei | 1177 | ATPPROSITE-ProRule annotation1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 1104 – 1110 | ATPPROSITE-ProRule annotation1 Publication | 7 | |
Nucleotide bindingi | 1163 – 1164 | ATPPROSITE-ProRule annotation1 Publication | 2 |
GO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- ATP binding Source: BHF-UCL
- cargo receptor activity Source: ARUK-UCL
- GTP binding Source: BHF-UCL
- identical protein binding Source: IntAct
- insulin-activated receptor activity Source: UniProtKB
- insulin binding Source: UniProtKB
- insulin-like growth factor I binding Source: BHF-UCL
- insulin-like growth factor II binding Source: BHF-UCL
- insulin-like growth factor receptor binding Source: BHF-UCL
- insulin receptor substrate binding Source: UniProtKB
- phosphatidylinositol 3-kinase binding Source: UniProtKB
- protein-containing complex binding Source: ARUK-UCL
- protein domain specific binding Source: CAFA
- protein tyrosine kinase activity Source: BHF-UCL
- PTB domain binding Source: UniProtKB
- structural molecule activity Source: UniProtKB
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- activation of MAPK activity Source: BHF-UCL
- activation of protein kinase activity Source: BHF-UCL
- activation of protein kinase B activity Source: BHF-UCL
- amyloid-beta clearance Source: ARUK-UCL
- carbohydrate metabolic process Source: UniProtKB-KW
- cellular response to insulin stimulus Source: BHF-UCL
- dendritic spine maintenance Source: ARUK-UCL
- glucose homeostasis Source: BHF-UCL
- G protein-coupled receptor signaling pathway Source: BHF-UCL
- heart morphogenesis Source: BHF-UCL
- insulin receptor signaling pathway Source: UniProtKB
- learning Source: ARUK-UCL
- memory Source: ARUK-UCL
- multicellular organism development Source: GO_Central
- neuron projection maintenance Source: ARUK-UCL
- peptidyl-tyrosine phosphorylation Source: BHF-UCL
- positive regulation of cell migration Source: BHF-UCL
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of developmental growth Source: BHF-UCL
- positive regulation of glucose import Source: BHF-UCL
- positive regulation of glycogen biosynthetic process Source: BHF-UCL
- positive regulation of glycolytic process Source: BHF-UCL
- positive regulation of kinase activity Source: GO_Central
- positive regulation of MAPK cascade Source: BHF-UCL
- positive regulation of mitotic nuclear division Source: BHF-UCL
- positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
- positive regulation of phosphatidylinositol 3-kinase signaling Source: GO_Central
- positive regulation of protein-containing complex disassembly Source: ARUK-UCL
- positive regulation of protein kinase B signaling Source: BHF-UCL
- positive regulation of protein phosphorylation Source: BHF-UCL
- positive regulation of receptor internalization Source: CACAO
- positive regulation of respiratory burst Source: BHF-UCL
- protein autophosphorylation Source: BHF-UCL
- protein phosphorylation Source: ARUK-UCL
- receptor-mediated endocytosis Source: ARUK-UCL
- regulation of embryonic development Source: BHF-UCL
- regulation of transcription, DNA-templated Source: BHF-UCL
- transformation of host cell by virus Source: BHF-UCL
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- transport across blood-brain barrier Source: ARUK-UCL
Keywordsi
Molecular function | Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Biological process | Carbohydrate metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 2681 |
PathwayCommonsi | P06213 |
Reactomei | R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-74713, IRS activation R-HSA-74749, Signal attenuation R-HSA-74751, Insulin receptor signalling cascade R-HSA-74752, Signaling by Insulin receptor R-HSA-77387, Insulin receptor recycling |
SABIO-RKi | P06213 |
SignaLinki | P06213 |
SIGNORi | P06213 |
Names & Taxonomyi
Protein namesi | Recommended name: Insulin receptor (EC:2.7.10.1)Short name: IR Alternative name(s): CD_antigen: CD220 Cleaved into the following 2 chains: |
Gene namesi | Name:INSR |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6091, INSR |
MIMi | 147670, gene |
neXtProti | NX_P06213 |
VEuPathDBi | HostDB:ENSG00000171105.13 |
Subcellular locationi
Lysosome
- Lysosome By similarity
Endosome
- Late endosome By similarity
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein Curated
Note: Binding of insulin to INSR induces internalization and lysosomal degradation of the receptor, a means for downregulating this signaling pathway after stimulation. In the presence of SORL1, internalized INSR molecules are redirected back to the cell surface, thereby preventing their lysosomal catabolism and strengthening insulin signal reception.By similarity
Endosome
- endosome membrane Source: Reactome
- late endosome Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Lysosome
- lysosome Source: UniProtKB-SubCell
Plasma Membrane
- caveola Source: BHF-UCL
- dendrite membrane Source: ARUK-UCL
- external side of plasma membrane Source: ARUK-UCL
- insulin receptor complex Source: UniProtKB
- integral component of plasma membrane Source: BHF-UCL
- neuronal cell body membrane Source: ARUK-UCL
- plasma membrane Source: ARUK-UCL
Other locations
- axon Source: GO_Central
- membrane Source: BHF-UCL
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 28 – 758 | ExtracellularCuratedAdd BLAST | 731 | |
Topological domaini | 763 – 956 | ExtracellularCuratedAdd BLAST | 194 | |
Transmembranei | 957 – 979 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 980 – 1382 | CytoplasmicCuratedAdd BLAST | 403 |
Keywords - Cellular componenti
Cell membrane, Endosome, Lysosome, MembranePathology & Biotechi
Involvement in diseasei
Rabson-Mendenhall syndrome (RMS)7 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_004079 | 42 | N → K in RMS; impairs transport to the plasma membrane and reduces the affinity to bind insulin. 2 PublicationsCorresponds to variant dbSNP:rs121913143EnsemblClinVar. | 1 | |
Natural variantiVAR_004084 | 236 | H → R in RMS and LEPRCH; Winnipeg; may impair receptor processing. 2 PublicationsCorresponds to variant dbSNP:rs121913145EnsemblClinVar. | 1 | |
Natural variantiVAR_079536 | 256 | R → C in RMS. 1 PublicationCorresponds to variant dbSNP:rs781007453EnsemblClinVar. | 1 | |
Natural variantiVAR_015914 | 350 | S → L in RMS and LEPRCH. 2 Publications | 1 | |
Natural variantiVAR_031520 | 386 | G → S in RMS; may impair receptor processing. 1 PublicationCorresponds to variant dbSNP:rs764221583Ensembl. | 1 | |
Natural variantiVAR_079539 | 635 | S → L in RMS; decreases post-translational processing. 1 Publication | 1 | |
Natural variantiVAR_079543 | 835 | S → I in RMS; impairs post-translational processing. 1 PublicationCorresponds to variant dbSNP:rs1135401739EnsemblClinVar. | 1 | |
Natural variantiVAR_079544 | 842 | A → V in RMS; decreases post-translational processing. 1 PublicationCorresponds to variant dbSNP:rs1135401738EnsemblClinVar. | 1 | |
Natural variantiVAR_079545 | 874 | P → L in RMS; impairs post-translational processing. 1 Publication | 1 | |
Natural variantiVAR_079546 | 878 | N → S in RMS; impairs post-translational processing. 1 PublicationCorresponds to variant dbSNP:rs887190835Ensembl. | 1 | |
Natural variantiVAR_015921 | 997 | P → T in RMS; reduces insulin binding. 1 Publication | 1 | |
Natural variantiVAR_079548 | 999 – 1382 | Missing in RMS. 1 PublicationAdd BLAST | 384 | |
Natural variantiVAR_015926 | 1143 | I → T in RMS; reduces insulin binding. 2 Publications | 1 | |
Natural variantiVAR_015928 | 1158 | R → W in RMS; abolishes insulin binding. 2 PublicationsCorresponds to variant dbSNP:rs111993466Ensembl. | 1 | |
Natural variantiVAR_015930 | 1201 | R → W in LEPRCH and RMS; reduces insulin binding possibly due to reduced receptor levels on the cell surface. 2 PublicationsCorresponds to variant dbSNP:rs1568426700EnsemblClinVar. | 1 |
Leprechaunism (LEPRCH)20 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_004080 | 55 | V → A in LEPRCH; Verona-1. 1 PublicationCorresponds to variant dbSNP:rs121913152EnsemblClinVar. | 1 | |
Natural variantiVAR_079535 | 56 | I → T in LEPRCH; abolishes post-translational processing. 1 PublicationCorresponds to variant dbSNP:rs1555689937EnsemblClinVar. | 1 | |
Natural variantiVAR_004081 | 58 | G → R in LEPRCH; Helmond; inhibits processing and transport. 1 PublicationCorresponds to variant dbSNP:rs52836744EnsemblClinVar. | 1 | |
Natural variantiVAR_004082 | 113 | R → P in LEPRCH; Atlanta-1; abolishes insulin binding. 2 PublicationsCorresponds to variant dbSNP:rs121913153EnsemblClinVar. | 1 | |
Natural variantiVAR_015909 | 119 | A → V in LEPRCH; markedly impairs insulin binding. 1 PublicationCorresponds to variant dbSNP:rs1347473020Ensembl. | 1 | |
Natural variantiVAR_031518 | 120 | L → Q in LEPRCH; inhibits receptor processing. 1 Publication | 1 | |
Natural variantiVAR_015539 | 146 | I → M in LEPRCH; mild. 2 PublicationsCorresponds to variant dbSNP:rs121913159EnsemblClinVar. | 1 | |
Natural variantiVAR_004084 | 236 | H → R in RMS and LEPRCH; Winnipeg; may impair receptor processing. 2 PublicationsCorresponds to variant dbSNP:rs121913145EnsemblClinVar. | 1 | |
Natural variantiVAR_004085 | 260 | L → P in LEPRCH; Geldeimalsen. 1 PublicationCorresponds to variant dbSNP:rs121913141EnsemblClinVar. | 1 | |
Natural variantiVAR_079537 | 286 | C → Y in LEPRCH; abolishes post-translational processing. 1 Publication | 1 | |
Natural variantiVAR_015912 | 301 | C → Y in LEPRCH. 1 Publication | 1 | |
Natural variantiVAR_015913 | 308 | Missing in LEPRCH; abolishes insulin binding. 3 Publications | 1 | |
Natural variantiVAR_015914 | 350 | S → L in RMS and LEPRCH. 2 Publications | 1 | |
Natural variantiVAR_015541 | 362 | Missing in LEPRCH. 1 Publication | 1 | |
Natural variantiVAR_004086 | 393 | G → R in LEPRCH; Verona-1. 1 PublicationCorresponds to variant dbSNP:rs267607184EnsemblClinVar. | 1 | |
Natural variantiVAR_015542 | 439 | W → S in LEPRCH; impairs transport of the receptor to the cell surface. 1 PublicationCorresponds to variant dbSNP:rs121913158EnsemblClinVar. | 1 | |
Natural variantiVAR_031521 | 458 | N → D in LEPRCH; partially inhibits receptor processing and autophosphorylation; strongly impairs ERK phosphorylation; induces wild-type levels of IRS-1 phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs121913160EnsemblClinVar. | 1 | |
Natural variantiVAR_004088 | 487 | K → E in LEPRCH; ARK-1. 1 PublicationCorresponds to variant dbSNP:rs121913136EnsemblClinVar. | 1 | |
Natural variantiVAR_079540 | 657 | V → F in LEPRCH; impairs post-translational processing. 1 PublicationCorresponds to variant dbSNP:rs1135401737EnsemblClinVar. | 1 | |
Natural variantiVAR_079541 | 659 | W → R in LEPRCH; impairs post-translational processing. 1 Publication | 1 | |
Natural variantiVAR_079542 | 818 | Y → C in LEPRCH; abolishes post-translational processing. 2 Publications | 1 | |
Natural variantiVAR_079547 | 890 – 1382 | Missing in LEPRCH. 1 PublicationAdd BLAST | 493 | |
Natural variantiVAR_015918 | 925 | I → T in LEPRCH; abolishes post-translational processing; abolishes insulin binding. 2 Publications | 1 | |
Natural variantiVAR_015919 | 926 | R → W in LEPRCH; markedly impairs insulin binding;impairs post-translational processing. 2 PublicationsCorresponds to variant dbSNP:rs911929963Ensembl. | 1 | |
Natural variantiVAR_015920 | 937 | T → M in LEPRCH; impaired receptor processing; impairs post-translational processing. 2 Publications | 1 | |
Natural variantiVAR_015925 | 1119 | R → W in LEPRCH. 2 PublicationsCorresponds to variant dbSNP:rs1229730671Ensembl. | 1 | |
Natural variantiVAR_015930 | 1201 | R → W in LEPRCH and RMS; reduces insulin binding possibly due to reduced receptor levels on the cell surface. 2 PublicationsCorresponds to variant dbSNP:rs1568426700EnsemblClinVar. | 1 | |
Natural variantiVAR_015932 | 1206 | E → K in LEPRCH. 1 Publication | 1 |
Diabetes mellitus, non-insulin-dependent (NIDDM)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015917 | 858 | T → A in NIDDM. 1 PublicationCorresponds to variant dbSNP:rs182552223EnsemblClinVar. | 1 | |
Natural variantiVAR_015927 | 1158 | R → Q in NIDDM. 1 Publication | 1 | |
Natural variantiVAR_004098 | 1191 | R → Q in NIDDM. 1 PublicationCorresponds to variant dbSNP:rs121913150EnsemblClinVar. | 1 |
Familial hyperinsulinemic hypoglycemia 5 (HHF5)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015929 | 1201 | R → Q in HHF5 and IRAN type A; interferes with kinase activation by insulin. 3 PublicationsCorresponds to variant dbSNP:rs121913156EnsemblClinVar. | 1 |
Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A)17 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015907 | 86 | D → G in IRAN type A. 1 Publication | 1 | |
Natural variantiVAR_015908 | 89 | L → P in IRAN type A. 1 Publication | 1 | |
Natural variantiVAR_015910 | 167 | V → L in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs938519025Ensembl. | 1 | |
Natural variantiVAR_015540 | 279 | R → C in IRAN type A; inhibits receptor internalization. 1 PublicationCorresponds to variant dbSNP:rs1568470274Ensembl. | 1 | |
Natural variantiVAR_031519 | 279 | R → H in IRAN type A; interferes with receptor processing. 1 PublicationCorresponds to variant dbSNP:rs1329693158Ensembl. | 1 | |
Natural variantiVAR_015911 | 280 | C → Y in IRAN type A. 1 Publication | 1 | |
Natural variantiVAR_004087 | 409 | F → V in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913142EnsemblClinVar. | 1 | |
Natural variantiVAR_079538 | 489 | N → D in IRAN type A; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1135401742EnsemblClinVar. | 1 | |
Natural variantiVAR_004089 | 489 | N → S in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913147EnsemblClinVar. | 1 | |
Natural variantiVAR_004090 | 762 | R → S in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913138EnsemblClinVar. | 1 | |
Natural variantiVAR_004092 | 1020 | R → Q in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913148EnsemblClinVar. | 1 | |
Natural variantiVAR_004093 | 1035 | G → V in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913135EnsemblClinVar. | 1 | |
Natural variantiVAR_079549 | 1054 | V → M in IRAN type A; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1135401741EnsemblClinVar. | 1 | |
Natural variantiVAR_015923 | 1055 | A → V in IRAN type A. 1 Publication | 1 | |
Natural variantiVAR_004094 | 1075 | A → D in IRAN type A. 1 Publication | 1 | |
Natural variantiVAR_004095 | 1161 | A → T in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913139EnsemblClinVar. | 1 | |
Natural variantiVAR_004096 | 1162 | A → E in IRAN type A; impairs proteolytic processing. 1 PublicationCorresponds to variant dbSNP:rs121913154EnsemblClinVar. | 1 | |
Natural variantiVAR_015929 | 1201 | R → Q in HHF5 and IRAN type A; interferes with kinase activation by insulin. 3 PublicationsCorresponds to variant dbSNP:rs121913156EnsemblClinVar. | 1 | |
Natural variantiVAR_004099 | 1205 | P → L in IRAN type A; moderate. 2 PublicationsCorresponds to variant dbSNP:rs1295645322Ensembl. | 1 | |
Natural variantiVAR_015931 | 1206 | E → D in IRAN type A; accelerates degradation of the protein and impairs kinase activity. 1 Publication | 1 | |
Natural variantiVAR_004100 | 1220 | W → L in IRAN type A; accelerates degradation of the protein and impairs kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs52800171Ensembl. | 1 | |
Natural variantiVAR_004101 | 1227 | W → S in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs121913140EnsemblClinVar. | 1 | |
Natural variantiVAR_015934 | 1378 | R → Q in IRAN type A. 1 PublicationCorresponds to variant dbSNP:rs52826008Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 991 | L → A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. 1 Publication | 1 | |
Mutagenesisi | 992 | Y → A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. 1 Publication | 1 | |
Mutagenesisi | 996 – 997 | NP → AA: Abolishes interaction with IRS1. Severely disrupts, but does not abolish interaction with SHC1. 1 Publication | 2 | |
Mutagenesisi | 996 | N → A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. 2 Publications | 1 | |
Mutagenesisi | 997 | P → A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. 2 Publications | 1 | |
Mutagenesisi | 998 | E → A: Does not affect interaction with IRS1, SHC1 or PIK3R1. 1 Publication | 1 | |
Mutagenesisi | 999 | Y → E: Abolishes interaction with IRS1 and SHC1. 4 Publications | 1 | |
Mutagenesisi | 999 | 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. 4 Publications | 1 | |
Mutagenesisi | 1000 | L → A or R: Severely reduces interaction with SHC1. Has no effect on interaction with IRS1. 1 Publication | 1 | |
Mutagenesisi | 1002 | A → D: Reduces interaction with IRS1 but has no effect on interaction with SHC1. 1 Publication | 1 | |
Mutagenesisi | 1011 | Y → A: Increases kinase activity. 1 Publication | 1 | |
Mutagenesisi | 1057 | K → A: Abolishes the kinase activity and abolishes interaction with IRS1, SHC1, GRB7 and PIK3R1. 3 Publications | 1 | |
Mutagenesisi | 1057 | K → M or R: Abolishes the kinase activity. 3 Publications | 1 | |
Mutagenesisi | 1159 | D → N: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 1163 | R → Q: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 1189 | Y → F: Reduced interaction with GRB7. 1 Publication | 1 | |
Mutagenesisi | 1190 | Y → F: Strongly reduced interaction with GRB7. 1 Publication | 1 |
Keywords - Diseasei
Diabetes mellitus, Disease variantOrganism-specific databases
DisGeNETi | 3643 |
GeneReviewsi | INSR |
MalaCardsi | INSR |
MIMi | 125853, phenotype 246200, phenotype 262190, phenotype 609968, phenotype 610549, phenotype |
OpenTargetsi | ENSG00000171105 |
Orphaneti | 263458, Hyperinsulinism due to INSR deficiency 2297, Insulin-resistance syndrome type A 508, Leprechaunism 769, Rabson-Mendenhall syndrome |
PharmGKBi | PA202 |
Miscellaneous databases
Pharosi | P06213, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1981 |
DrugBanki | DB08513, [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID DB03909, Adenosine-5'-[Beta, Gamma-Methylene]Triphosphate DB05120, AT1391 DB12267, Brigatinib DB09129, Chromic chloride DB12010, Fostamatinib DB01306, Insulin aspart DB09564, Insulin degludec DB01307, Insulin detemir DB00047, Insulin glargine DB01309, Insulin glulisine DB00030, Insulin human DB00046, Insulin lispro DB00071, Insulin pork DB01277, Mecasermin DB14751, Mecasermin rinfabate DB05115, NN344 |
DrugCentrali | P06213 |
GuidetoPHARMACOLOGYi | 1800 |
Genetic variation databases
BioMutai | INSR |
DMDMi | 308153655 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | 3 PublicationsAdd BLAST | 27 | |
ChainiPRO_0000016687 | 28 – 758 | Insulin receptor subunit alphaAdd BLAST | 731 | |
ChainiPRO_0000016689 | 763 – 1382 | Insulin receptor subunit betaAdd BLAST | 620 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 35 ↔ 53 | |||
Glycosylationi | 43 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Glycosylationi | 52 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 105 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 138 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 153 ↔ 182 | |||
Disulfide bondi | 186 ↔ 209 | |||
Disulfide bondi | 196 ↔ 215 | |||
Disulfide bondi | 219 ↔ 228 | |||
Disulfide bondi | 223 ↔ 234 | |||
Disulfide bondi | 235 ↔ 243 | |||
Disulfide bondi | 239 ↔ 252 | |||
Glycosylationi | 242 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Disulfide bondi | 255 ↔ 264 | |||
Disulfide bondi | 268 ↔ 280 | |||
Glycosylationi | 282 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 286 ↔ 311 | |||
Disulfide bondi | 293 ↔ 301 | |||
Disulfide bondi | 315 ↔ 328 | |||
Glycosylationi | 322 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 331 ↔ 335 | |||
Disulfide bondi | 339 ↔ 360 | |||
Glycosylationi | 364 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Modified residuei | 400 | PhosphoserineCombined sources | 1 | |
Modified residuei | 401 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 407 | PhosphoserineCombined sources | 1 | |
Glycosylationi | 424 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 445 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 462 ↔ 495 | 1 Publication | ||
Glycosylationi | 541 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 551 | Interchain1 Publication | ||
Glycosylationi | 633 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 651 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 674 ↔ 899 | |||
Glycosylationi | 698 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 769 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 782 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 825 ↔ 834 | |||
Glycosylationi | 920 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 933 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 992 | Phosphotyrosine; by autocatalysisCurated | 1 | |
Modified residuei | 999 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 1011 | Phosphotyrosine; by autocatalysisCurated | 1 | |
Modified residuei | 1185 | Phosphotyrosine; by autocatalysis7 Publications | 1 | |
Modified residuei | 1189 | Phosphotyrosine; by autocatalysis7 Publications | 1 | |
Modified residuei | 1190 | Phosphotyrosine; by autocatalysis7 Publications | 1 | |
Modified residuei | 1355 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 1361 | Phosphotyrosine; by autocatalysis1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
CPTACi | CPTAC-1771 CPTAC-1772 |
EPDi | P06213 |
jPOSTi | P06213 |
MassIVEi | P06213 |
MaxQBi | P06213 |
PaxDbi | P06213 |
PeptideAtlasi | P06213 |
PRIDEi | P06213 |
ProteomicsDBi | 51872 [P06213-1] 51873 [P06213-2] |
PTM databases
GlyConnecti | 1402, 8 N-Linked glycans (6 sites) |
GlyGeni | P06213, 21 sites, 3 O-linked glycans (3 sites) |
iPTMneti | P06213 |
PhosphoSitePlusi | P06213 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000171105, Expressed in oviduct epithelium and 250 other tissues |
ExpressionAtlasi | P06213, baseline and differential |
Genevisiblei | P06213, HS |
Organism-specific databases
HPAi | ENSG00000171105, Tissue enhanced (pancreas) |
Interactioni
Subunit structurei
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.
Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity).
Interacts with the cone snail venom insulin Con-Ins G1 (PubMed:27617429).
Interacts with the insulin receptor SORL1; this interaction strongly increases its surface exposure, hence strengthens insulin signal reception (PubMed:27322061).
Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the INSR C-terminal region (PubMed:25187647).
Interacts with GNAI3; the interaction is probably mediated by CCDC88A/GIV (PubMed:25187647).
By similarity29 PublicationsBinary interactionsi
Hide detailsP06213
INSR - isoform Long [P06213-1]
Isoform Short [P06213-2]
With | #Exp. | IntAct |
---|---|---|
INS [P01308] | 6 | EBI-9984921,EBI-7090529 |
MAD2L1 [Q13257] | 3 | EBI-9984921,EBI-78203 |
SMPDL3B - isoform 2 [Q92485-2] | 2 | EBI-9984921,EBI-21501656 |
INS [P01317] from Bos taurus. | 2 | EBI-9984921,EBI-3989070 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- insulin binding Source: UniProtKB
- insulin-like growth factor I binding Source: BHF-UCL
- insulin-like growth factor II binding Source: BHF-UCL
- insulin-like growth factor receptor binding Source: BHF-UCL
- insulin receptor substrate binding Source: UniProtKB
- phosphatidylinositol 3-kinase binding Source: UniProtKB
- protein domain specific binding Source: CAFA
- PTB domain binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 109854, 119 interactors |
CORUMi | P06213 |
DIPi | DIP-480N |
ELMi | P06213 |
IntActi | P06213, 81 interactors |
MINTi | P06213 |
STRINGi | 9606.ENSP00000303830 |
Chemistry databases
BindingDBi | P06213 |
Miscellaneous databases
RNActi | P06213, protein |