Target name

P00517: cAMP-dependent protein kinase catalytic subunit alpha


  Protein function

Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (By similarity).

  Database links

Uniprot primary ID P00517
PDB ID 2UVY 2OJF 2UVZ 3E8E 1XH9 1XH8 1XH7 1XH6 1XH5 1XH4 1YDR 4YXS 3E8C 1KMW 1KMU 2JDT 2JDV 2UVX 1Q61 1Q62 2JDS 2UW6 2UW7 2UW4 2UW5 1Q24 2UW3 2UW0 3ZO1 2UZV 1STC 3DNE 1SVG 1SVE 1SZM 2F7X 2F7Z 4IJ9 1SVH 2GFC 2VO0 2VO7 3ZO3 3ZO4 2UZW 1Q8U 3ZO2 2VNY 4C37 4C35 4C33
DrugBank ID
BioGrid ID 159584
GuidetoPHARMACOLOGY ID
PharmGKB ID
KEGG ID bta:282322
DIP ID
STRING ID 9913.ENSBTAP00000008727
IntAct ID P00517
DMDM
BRENDA 2.7.11.11
Reactome R-BTA-381676 R- R-BTA-70263 R-BTA-432040 R-BTA-2565942 R-BTA-164378 R-BTA-380259 R-BTA-983231 R-BTA-180024 R-BTA-512988 R-BTA-422356 R-BTA-5610780 R-BTA-5610783 R-BTA-5610785 R-BTA-5610787 R-BTA-163615 R-BTA-5620912 R-BTA-392517 R-BTA-380270 R-BTA-5621575
SignaLink
BioCyc
Entrez Gene (Gene ID) 282322
BindingDB P00517

  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 0.957 0.007 0.939 0.009 0.948 0.004 0.948 0.004 0.978 0.004 0.894 0.010 Download
Estate fingerprints 0.894 0.011 0.790 0.012 0.842 0.009 0.849 0.010 0.907 0.005 0.688 0.015 Download
MACCS fingerprints 0.859 0.009 0.877 0.008 0.868 0.006 0.868 0.006 0.955 0.005 0.735 0.008 Download
Daylight fingerprints 0.793 0.011 0.977 0.000 0.885 0.007 0.874 0.007 0.941 0.003 0.782 0.010 Download
ECFP2 fingerprints 0.971 0.006 0.913 0.007 0.942 0.004 0.942 0.004 0.990 0.000 0.886 0.005 Download
ECFP4 fingerprints 0.954 0.005 0.986 0.000 0.970 0.000 0.970 0.000 0.990 0.000 0.933 0.005 Download
ECFP6 fingerprints 0.946 0.005 0.986 0.000 0.966 0.005 0.966 0.005 0.990 0.000 0.931 0.003 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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