Target name

P08069: Insulin-like growth factor 1 receptor

  Protein function

Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.

  Database links

Uniprot primary ID P08069
PDB ID 1JQH 3NW6 3NW7 3NW5 1M7N 2ZM3 3QQU 3O23 3F5P 3I81 3LW0 1IGR 1K3A 4D2R 3D94 3LVP 1P4O 4XSS 2OJ9
DrugBank ID DB00030 DB00047 DB01277 DB00046
BioGrid ID 109701
PharmGKB ID PA29698
KEGG ID hsa:3480
STRING ID 9606.ENSP00000268035
IntAct ID P08069
DMDM 124240
Reactome R-HSA-2428928 R-HSA-2404192 R-HSA-2428933
SignaLink P08069
Entrez Gene (Gene ID) 3480
BindingDB P08069

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.800 0.000 0.860 0.005 0.830 0.000 0.830 0.000 0.891 0.003 0.669 0.003 Download
Estate fingerprints 0.800 0.000 0.690 0.003 0.745 0.005 0.760 0.000 0.830 0.000 0.494 0.005 Download
MACCS fingerprints 0.822 0.004 0.720 0.005 0.771 0.003 0.781 0.003 0.860 0.000 0.550 0.005 Download
Daylight fingerprints 0.754 0.005 0.766 0.003 0.760 0.000 0.760 0.000 0.800 0.000 0.523 0.005 Download
ECFP2 fingerprints 0.851 0.003 0.875 0.004 0.863 0.005 0.861 0.003 0.939 0.003 0.730 0.000 Download
ECFP4 fingerprints 0.812 0.004 0.970 0.005 0.891 0.003 0.882 0.004 0.950 0.000 0.800 0.000 Download
ECFP6 fingerprints 0.789 0.003 0.991 0.000 0.890 0.000 0.880 0.000 0.950 0.000 0.800 0.000 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.

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