PRKACA - cAMP-dependent protein kinase catalytic subunit alpha - human protein (Function)
 
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PRKACA »  cAMP-dependent protein kinase catalytic subunit alpha   [ EC 2.7.11.11 ]  (PKA C-alpha)
 
Gene name:  PRKACA
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
12
  • UniProtKB
Isoform  Iso 2   Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.  
13
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
cAMP-dependent protein kinase activitydefinition[GO:0004691]  
3
  • BHF-UCL
  • UniProtKB
  • Ortholog Curator
Protein bindingdefinition[GO:0005515]  
9
  • IntAct
  • BHF-UCL
Protein kinase A regulatory subunit bindingdefinition[GO:0034237]  
1
  • BHF-UCL
Protein kinase bindingdefinition[GO:0019901]  
1
  • BHF-UCL
Protein serine/threonine/tyrosine kinase activitydefinition[GO:0004712]  
1
  • MGI
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
GO biological process 
Calcium-mediated signaling using intracellular calcium sourcedefinition[GO:0035584]  
1
  • BHF-UCL
Cell communication by electrical coupling involved in cardiac conductiondefinition[GO:0086064]  
1
  • BHF-UCL
Cellular response to epinephrine stimulusdefinition[GO:0071872]  
1
  • BHF-UCL
Cellular response to glucose stimulusdefinition[GO:0071333]  
1
  • UniProtKB
Cellular response to parathyroid hormone stimulusdefinition[GO:0071374] silver  
1
  • Ortholog Compara
Cytosolic calcium ion homeostasisdefinition[GO:0051480]  
1
  • BHF-UCL
Mesoderm formationdefinition[GO:0001707] silver  
1
  • Ortholog Compara
Negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterningdefinition[GO:1901621] silver  
1
  • Ortholog Compara
Neural tube closuredefinition[GO:0001843] silver  
1
  • Ortholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
2
  • BHF-UCL
  • UniProtKB
Peptidyl-threonine phosphorylationdefinition[GO:0018107] silver  
1
  • Ortholog Compara
Positive regulation of cell cycle arrestdefinition[GO:0071158]  
1
  • Ortholog Curator
Positive regulation of protein export from nucleusdefinition[GO:0046827] silver  
1
  • Ortholog Compara
Protein autophosphorylationdefinition[GO:0046777] silver  
1
  • Ortholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of cardiac muscle contractiondefinition[GO:0055117]  
1
  • BHF-UCL
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium iondefinition[GO:0010881]  
1
  • BHF-UCL
Regulation of heart ratedefinition[GO:0002027]  
1
  • BHF-UCL
Regulation of osteoblast differentiationdefinition[GO:0045667]  
1
  • UniProtKB
Regulation of proteasomal protein catabolic processdefinition[GO:0061136]  
1
  • UniProtKB
Regulation of protein bindingdefinition[GO:0043393]  
1
  • BHF-UCL
Regulation of protein processingdefinition[GO:0070613] silver  
1
  • Ortholog Compara
Regulation of ryanodine-sensitive calcium-release channel activitydefinition[GO:0060314]  
1
  • BHF-UCL
Regulation of synaptic transmissiondefinition[GO:0050804] silver  
1
  • Ortholog Compara
Regulation of tight junction assemblydefinition[GO:2000810]  
1
  • UniProtKB
Sperm capacitationdefinition[GO:0048240]  
1
  • Ortholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.11: ATP + a protein ADP + a phosphoprotein.  
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  • UniProtKB
EC 2.7.11.11: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
It is regulated in the following manner
Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide).  
7
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Apoptosis  hsa04210+5566  
Calcium signaling pathway  hsa04020+5566  
Chemokine signaling pathway  hsa04062+5566  
Cholinergic synapse  hsa04725+5566  
Dopaminergic synapse  hsa04728+5566  
GABAergic synapse  hsa04727+5566  
Gap junction  hsa04540+5566  
Glutamatergic synapse  hsa04724+5566  
GnRH signaling pathway  hsa04912+5566  
Hedgehog signaling pathway  hsa04340+5566  
Insulin signaling pathway  hsa04910+5566  
Long-term potentiation  hsa04720+5566  
MAPK signaling pathway  hsa04010+5566  
Melanogenesis  hsa04916+5566  
Olfactory transduction  hsa04740+5566  
Oocyte meiosis  hsa04114+5566  
Progesterone-mediated oocyte maturation  hsa04914+5566  
Taste transduction  hsa04742+5566  
Vascular smooth muscle contraction  hsa04270+5566  
Wnt signaling pathway  hsa04310+5566  
According to Reactome, this protein belongs to the following pathways:
CREB phosphorylation through the activation of Adenylate Cyclase  REACT_20625  
DARPP-32 events  REACT_15334  
Degradation of GLI1 by the proteasome  REACT_267605  
Degradation of GLI2 by the proteasome  REACT_206597  
Factors involved in megakaryocyte development and platelet production  REACT_24970  
GLI3 is processed to GLI3R by the proteasome  REACT_231645  
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion  REACT_18274  
Gluconeogenesis  REACT_1520  
Hedgehog 'off' state  REACT_267634  
Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis  REACT_494  
Interleukin-3, 5 and GM-CSF signaling  REACT_23837  
Loss of Nlp from mitotic centrosomes  REACT_15364  
Loss of proteins required for interphase microtubule organization from the centrosome  REACT_15451  
PKA activation  REACT_15530  
PKA activation in glucagon signalling  REACT_1946  
PKA-mediated phosphorylation of CREB  REACT_15497  
PKA-mediated phosphorylation of key metabolic factors  REACT_1525  
Rap1 signalling  REACT_23898  
Recruitment of mitotic centrosome proteins and complexes  REACT_15296  
Regulation of insulin secretion  REACT_18325  
Regulation of PLK1 Activity at G2/M Transition  REACT_160315  
Vasopressin regulates renal water homeostasis via Aquaporins  REACT_24023  
VEGFA-VEGFR2 Pathway  REACT_228166  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PRKACA
GenomeRNAi: 5566
PRO: PR:P17612
Chemistry
GuidetoPHARMACOLOGY: 1476