Target name

P06213: Insulin receptor

  Protein 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

  Database links

Uniprot primary ID P06213
PDB ID 2B4S 1IRK 3W14 3W11 2DTG 3W13 3W12 2MFR 4OGA 3ETA 4XSS 4XST 4XLV 1IR3 3EKN 1P14 3LOH 1I44 1RQQ 2HR7 3EKK 2Z8C 1GAG 3BU6 3BU3 2AUH 3BU5 4IBM
DrugBank ID DB01309 DB00047 DB00046 DB00030 DB01277 DB01307 DB01306
BioGrid ID 109854
PharmGKB ID PA202
KEGG ID hsa:3643
Entrez Gene (Gene ID) 3643
STRING 9606ENSP00000303830
MINT MINT-1516246
IntAct P06213
DMDM 308153655
BREDNA 27101
Rectome R-HSA-74749 R-HSA-74713 R-HSA-74751 R-HSA-74752 R-HSA-77387
SignaLink P06213
BindingDB P06213

  Model Performance Metrics

Fingerprint type F1_CV AUC_CV Accuracy_CV Sensitivity_CV Specificity_CV F1_test AUC_test Accuracy_test Sensitivity_test Specificity_test Download model
FP2 fingerprints 0.841 0.886 0.846 0.809 0.883 0.872 0.913 0.876 0.859 0.893 Download
MACCS fingerprints 0.782 0.841 0.767 0.834 0.699 0.809 0.875 0.797 0.879 0.718 Download
Daylight fingerprints 0.836 0.857 0.837 0.827 0.848 0.845 0.893 0.851 0.828 0.874 Download
ECFP2 fingerprints 0.832 0.897 0.834 0.822 0.846 0.894 0.958 0.896 0.899 0.893 Download
ECFP4 fingerprints 0.845 0.914 0.855 0.787 0.923 0.911 0.943 0.916 0.879 0.951 Download
ECFP6 fingerprints 0.834 0.907 0.854 0.735 0.973 0.880 0.937 0.891 0.818 0.961 Download

  Download datasets

Positive dataset Negative dataset

Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

The recommended browsers: Safari, Firefox, Chrome,IE(Ver.>8).