Names & Taxonomy
- Uniprot ID:
- P17612
- Entry Name:
- KAPCA_HUMAN
- Status:
- reviewed
- Protein Names:
- cAMP-dependent protein kinase catalytic subunit alpha (PKA C-alpha) (EC 2.7.11.11)
- Gene Names:
- PRKACA PKACA
- Gene Names Primary:
- PRKACA
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 351
- Sequence:
- MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFSEF
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm. Cell membrane. Nucleus
Function
- 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- ENZYME REGULATION: 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--5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-
- Active Site:
- ACT_SITE 167 167 Proton acceptor.
- Gene Ontology Go:
- calcium channel complex
cAMP-dependent protein kinase complex
centrosome
ciliary base
cytosol
extracellular exosome
Golgi apparatus
mitochondrion
motile cilium
neuromuscular junction
neuron projection
nuclear speck
nucleoplasm
nucleotide-activated protein kinase complex
nucleus
perinuclear region of cytoplasm
plasma membrane raft
sperm midpiece
ATP binding
cAMP-dependent protein kinase activity
protein kinase A regulatory subunit binding
protein kinase binding
protein serine/threonine/tyrosine kinase activity
ubiquitin protein ligase binding
activation of phospholipase C activity
activation of protein kinase A activity
blood coagulation
calcium-mediated signaling using intracellular calcium source
carbohydrate metabolic process
cardiac conduction
cell communication by electrical coupling involved in cardiac conduction
cellular response to epinephrine stimulus
cellular response to glucagon stimulus
cellular response to glucose stimulus
cellular response to parathyroid hormone stimulus
energy reserve metabolic process
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
G2/M transition of mitotic cell cycle
gluconeogenesis
glucose metabolic process
innate immune response
intracellular signal transduction
mesoderm formation
mitotic cell cycle
mRNA processing
negative regulation of meiotic cell cycle
negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
neural tube closure
neurotrophin TRK receptor signaling pathway
organelle organization
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of cell cycle arrest
positive regulation of cell proliferation
positive regulation of protein export from nucleus
protein autophosphorylation
protein phosphorylation
regulation of bicellular tight junction assembly
regulation of cardiac conduction
regulation of cardiac muscle contraction
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
regulation of cellular respiration
regulation of cytosolic calcium ion concentration
regulation of heart rate
regulation of insulin secretion
regulation of osteoblast differentiation
regulation of proteasomal protein catabolic process
regulation of protein binding
regulation of protein processing
regulation of ryanodine-sensitive calcium-release channel activity
regulation of synaptic transmission, glutamatergic
renal water homeostasis
signal transduction
small molecule metabolic process
sperm capacitation
stimulatory C-type lectin receptor signaling pathway
transmembrane transport
triglyceride catabolic process
water transport - Gene Ontology Biological Process:
- activation of phospholipase C activity
activation of protein kinase A activity
blood coagulation
calcium-mediated signaling using intracellular calcium source
carbohydrate metabolic process
cardiac conduction
cell communication by electrical coupling involved in cardiac conduction
cellular response to epinephrine stimulus
cellular response to glucagon stimulus
cellular response to glucose stimulus
cellular response to parathyroid hormone stimulus
energy reserve metabolic process
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
G2/M transition of mitotic cell cycle
gluconeogenesis
glucose metabolic process
innate immune response
intracellular signal transduction
mesoderm formation
mitotic cell cycle
mRNA processing
negative regulation of meiotic cell cycle
negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
neural tube closure
neurotrophin TRK receptor signaling pathway
organelle organization
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of cell cycle arrest
positive regulation of cell proliferation
positive regulation of protein export from nucleus
protein autophosphorylation
protein phosphorylation
regulation of bicellular tight junction assembly
regulation of cardiac conduction
regulation of cardiac muscle contraction
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
regulation of cellular respiration
regulation of cytosolic calcium ion concentration
regulation of heart rate
regulation of insulin secretion
regulation of osteoblast differentiation
regulation of proteasomal protein catabolic process
regulation of protein binding
regulation of protein processing
regulation of ryanodine-sensitive calcium-release channel activity
regulation of synaptic transmission, glutamatergic
renal water homeostasis
signal transduction
small molecule metabolic process
sperm capacitation
stimulatory C-type lectin receptor signaling pathway
transmembrane transport
triglyceride catabolic process
water transport - Gene Ontology Molecular Function:
- ATP binding
cAMP-dependent protein kinase activity
protein kinase A regulatory subunit binding
protein kinase binding
protein serine/threonine/tyrosine kinase activity
ubiquitin protein ligase binding - Gene Ontology Cellular Component:
- calcium channel complex
cAMP-dependent protein kinase complex
centrosome
ciliary base
cytosol
extracellular exosome
Golgi apparatus
mitochondrion
motile cilium
neuromuscular junction
neuron projection
nuclear speck
nucleoplasm
nucleotide-activated protein kinase complex
nucleus
perinuclear region of cytoplasm
plasma membrane raft
sperm midpiece - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Cell membrane
Cell projection
Cilium
Complete proteome
Cushing syndrome
Cytoplasm
Disease mutation
Flagellum
Kinase
Lipoprotein
Membrane
Mitochondrion
Myristate
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
cAMP - Interacts With:
- Q9NQ31; P09917; P49841; Q5S007; P10644; P12369
Publication
- PubMed ID:
- 2843813 14702039 15489334 10906071 10982398 10841548 12372837 15096524 15642694 15905176 16387847 17565987 17693412 17909264 17333334 18691976 18836454 18178622 19210988 19369195 19690332 20356841 19949837 21269460 21514275 21812984 21423175 24275569 25255805 24747643 25807930 25944712 16765046 20137943 20481595 20732331 21774789 17344846 24571724 24700472 24855271