Target Information
Target General Infomation | |||||
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Target ID |
T20669
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Former ID |
TTDR01375
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Target Name |
mRNA of PKA Catalytic Subunit C-alpha
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Gene Name |
PRKACA
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Synonyms |
PKA Calpha (mRNA); PRKACA (mRNA); cAMPdependent protein kinase catalytic subunit alpha (mRNA); PRKACA
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Target Type |
Discontinued
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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). Phosphorylates APOBEC3G and AICDA. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.
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BioChemical Class |
Kinase
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Target Validation |
T20669
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UniProt ID | |||||
EC Number |
EC 2.7.11.11
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Sequence |
MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVML
VKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMV MEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGY IQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFF ADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFAT TDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFSEF |
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Drugs and Mode of Action | |||||
Drug(s) | BALANOL | Drug Info | Terminated | Discovery agent | [1], [2] |
Inhibitor | 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Drug Info | [3] | ||
BALANOL | Drug Info | [4] | |||
H-89 | Drug Info | [5] | |||
NM-PP1 | Drug Info | [6] | |||
Ro-4396686 | Drug Info | [7] | |||
Pathways | |||||
KEGG Pathway | MAPK signaling pathway | ||||
Ras signaling pathway | |||||
Calcium signaling pathway | |||||
cAMP signaling pathway | |||||
Chemokine signaling pathway | |||||
Oocyte meiosis | |||||
Apoptosis | |||||
Adrenergic signaling in cardiomyocytes | |||||
Vascular smooth muscle contraction | |||||
Wnt signaling pathway | |||||
Hedgehog signaling pathway | |||||
Gap junction | |||||
Platelet activation | |||||
Circadian entrainment | |||||
Long-term potentiation | |||||
Retrograde endocannabinoid signaling | |||||
Glutamatergic synapse | |||||
Cholinergic synapse | |||||
Serotonergic synapse | |||||
GABAergic synapse | |||||
Dopaminergic synapse | |||||
Olfactory transduction | |||||
Taste transduction | |||||
Inflammatory mediator regulation of TRP channels | |||||
Insulin signaling pathway | |||||
Insulin secretion | |||||
GnRH signaling pathway | |||||
Ovarian steroidogenesis | |||||
Progesterone-mediated oocyte maturation | |||||
Estrogen signaling pathway | |||||
Melanogenesis | |||||
Thyroid hormone synthesis | |||||
Thyroid hormone signaling pathway | |||||
Oxytocin signaling pathway | |||||
Glucagon signaling pathway | |||||
Regulation of lipolysis in adipocytes | |||||
Renin secretion | |||||
Endocrine and other factor-regulated calcium reabsorption | |||||
Vasopressin-regulated water reabsorption | |||||
Salivary secretion | |||||
Gastric acid secretion | |||||
Bile secretion | |||||
Parkinson' | |||||
s disease | |||||
Prion diseases | |||||
Cocaine addiction | |||||
Amphetamine addiction | |||||
Morphine addiction | |||||
Alcoholism | |||||
Vibrio cholerae infection | |||||
Amoebiasis | |||||
HTLV-I infection | |||||
Epstein-Barr virus infection | |||||
Pathways in cancer | |||||
Viral carcinogenesis | |||||
Proteoglycans in cancer | |||||
Dilated cardiomyopathy | |||||
PANTHER Pathway | Endothelin signaling pathway | ||||
Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
Heterotrimeric G-protein signaling pathway-rod outer segment phototransduction | |||||
Inflammation mediated by chemokine and cytokine signaling pathway | |||||
Metabotropic glutamate receptor group III pathway | |||||
Metabotropic glutamate receptor group II pathway | |||||
Metabotropic glutamate receptor group I pathway | |||||
Muscarinic acetylcholine receptor 2 and 4 signaling pathway | |||||
5HT1 type receptor mediated signaling pathway | |||||
Beta1 adrenergic receptor signaling pathway | |||||
Beta2 adrenergic receptor signaling pathway | |||||
Histamine H2 receptor mediated signaling pathway | |||||
GABA-B receptor II signaling | |||||
Dopamine receptor mediated signaling pathway | |||||
Enkephalin release | |||||
Nicotine pharmacodynamics pathway | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | GMCSF-mediated signaling events | ||||
LPA4-mediated signaling events | |||||
Signaling events regulated by Ret tyrosine kinase | |||||
LKB1 signaling events | |||||
Thromboxane A2 receptor signaling | |||||
SHP2 signaling | |||||
Signaling events mediated by HDAC Class I | |||||
Role of Calcineurin-dependent NFAT signaling in lymphocytes | |||||
Glucocorticoid receptor regulatory network | |||||
ErbB2/ErbB3 signaling events | |||||
IL3-mediated signaling events | |||||
Syndecan-1-mediated signaling events | |||||
Retinoic acid receptors-mediated signaling | |||||
Hedgehog signaling events mediated by Gli proteins | |||||
VEGFR1 specific signals | |||||
Calcium signaling in the CD4+ TCR pathway | |||||
Signaling events mediated by VEGFR1 and VEGFR2 | |||||
Syndecan-2-mediated signaling events | |||||
Aurora A signaling | |||||
Class I PI3K signaling events mediated by Akt | |||||
Alpha4 beta1 integrin signaling events | |||||
PathWhiz Pathway | Muscle/Heart Contraction | ||||
Reactome | Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis | ||||
PKA activation | |||||
PKA activation in glucagon signalling | |||||
DARPP-32 events | |||||
Regulation of PLK1 Activity at G2/M Transition | |||||
Loss of Nlp from mitotic centrosomes | |||||
Recruitment of mitotic centrosome proteins and complexes | |||||
Loss of proteins required for interphase microtubule organization?from the centrosome | |||||
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | |||||
Regulation of insulin secretion | |||||
Vasopressin regulates renal water homeostasis via Aquaporins | |||||
VEGFA-VEGFR2 Pathway | |||||
Interleukin-3, 5 and GM-CSF signaling | |||||
Degradation of GLI1 by the proteasome | |||||
Degradation of GLI2 by the proteasome | |||||
Hedgehog ' | |||||
off' | |||||
state | |||||
Anchoring of the basal body to the plasma membrane | |||||
CD209 (DC-SIGN) signaling | |||||
MAPK6/MAPK4 signaling | |||||
Gluconeogenesis | |||||
Factors involved in megakaryocyte development and platelet production | |||||
WikiPathways | SIDS Susceptibility Pathways | ||||
Hypothetical Network for Drug Addiction | |||||
Calcium Regulation in the Cardiac Cell | |||||
Endochondral Ossification | |||||
MAPK Signaling Pathway | |||||
G Protein Signaling Pathways | |||||
Myometrial Relaxation and Contraction Pathways | |||||
IL-3 Signaling Pathway | |||||
Mesodermal Commitment Pathway | |||||
Human Complement System | |||||
DAG and IP3 signaling | |||||
Regulation of Water Balance by Renal Aquaporins | |||||
Dopamine metabolism | |||||
Regulation of Microtubule Cytoskeleton | |||||
FSH signaling pathway | |||||
miRs in Muscle Cell Differentiation | |||||
SREBP signalling | |||||
Opioid Signalling | |||||
Mitotic G2-G2/M phases | |||||
Integration of energy metabolism | |||||
Factors involved in megakaryocyte development and platelet production | |||||
Nicotine Activity on Dopaminergic Neurons | |||||
References | |||||
REF 1 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8142). | ||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003814) | ||||
REF 3 | J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. | ||||
REF 4 | J Med Chem. 2005 Sep 8;48(18):5613-38.Joys of molecules. 2. Endeavors in chemical biology and medicinal chemistry. | ||||
REF 5 | Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem. 1990 Mar 25;265(9):5267-72. | ||||
REF 6 | Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. | ||||
REF 7 | Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. Epub 2006 Feb 3.Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. |
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