Target name

P19525: Interferon-induced, double-stranded RNA-activated protein kinase

  Protein function

IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.

  Database links

Uniprot primary ID P19525
PDB ID 2A19 1QU6 3UIU 2A1A
DrugBank ID
BioGrid ID 111596
PharmGKB ID PA33779
KEGG ID hsa:5610
Entrez Gene (Gene ID) 5610
STRING 9606ENSP00000233057
IntAct P19525
DMDM 125527
Rectome R-HSA-1169408 R-HSA-169131
SignaLink P19525
BindingDB P19525

  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 0.492 0.568 0.516 0.469 0.563 0.606 0.637 0.594 0.556 0.643 Download
MACCS fingerprints 0.519 0.516 0.508 0.531 0.484 0.588 0.448 0.563 0.556 0.571 Download
Daylight fingerprints 0.592 0.616 0.602 0.578 0.625 0.686 0.659 0.656 0.667 0.643 Download
ECFP2 fingerprints 0.290 0.150 0.273 0.297 0.250 0.533 0.679 0.563 0.444 0.714 Download
ECFP4 fingerprints 0.409 0.436 0.414 0.406 0.422 0.533 0.722 0.563 0.444 0.714 Download
ECFP6 fingerprints 0.484 0.520 0.500 0.469 0.531 0.625 0.732 0.625 0.556 0.714 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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