cAMP-dependent protein kinase catalytic subunit alpha

Details

Name
cAMP-dependent protein kinase catalytic subunit alpha
Synonyms
  • 2.7.11.11
  • PKA C-alpha
  • PKACA
Gene Name
PRKACA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007218|cAMP-dependent protein kinase catalytic subunit alpha
MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVML
VKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMV
MEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGY
IQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFF
ADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFAT
TDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFSEF
Number of residues
351
Molecular Weight
40589.38
Theoretical pI
9.22
GO Classification
Functions
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
Processes
activation of phospholipase C activity / activation of protein kinase A activity / blood coagulation / calcium-mediated signaling using intracellular calcium source / carbohydrate metabolic process / 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 / cytosolic calcium ion homeostasis / 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 / 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 muscle contraction / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / regulation of cellular respiration / 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
Components
calcium channel complex / cAMP-dependent protein kinase complex / centrosome / ciliary base / cytosol / extracellular exosome / Golgi apparatus / mitochondrion / motile cilium / neuromuscular junction / neuron projection / nucleoplasm / nucleotide-activated protein kinase complex / nucleus / perinuclear region of cytoplasm / plasma membrane raft / sperm midpiece
General Function
Ubiquitin protein ligase binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0017217|cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)
ATGTTCACCTTGGGATACCATGGGGCCGAGGAGTGGGCATCGGGCGAGACTTCCCTTGAA
CCAGCTCTGGAGCAATGCCCTTGCGATTGCCACGGAGAGGAACAGGGCCAGCTGGGGGCC
AAGGTGACAGCTGAGCCCCCCAAGGGCACCTGCTACCCGAGCCCCCGAGGCCTCCATCCC
AGGCCCGGCCTCCCCAGAGAAGGGGCCAGAGGAACAGCCAAATCCCAAGGCTATAAATAC
CTCGGCTGGCGTCGGCCCTGGCCATGGAATGTCGTGAAAGAATTCTTAGCCAAAGCCAAA
GAAGATTTTCTTAAAAAATGGGAAAGTCCCGCTCAGAACACAGCCCACTTGGATCAGTTT
GAACGAATCAAGACCCTCGGCACGGGCTCCTTCGGGCGGGTGATGCTGGTGAAACACAAG
GAGACCGGGAACCACTATGCCATGAAGATCCTCGACAAACAGAAGGTGGTGAAACTGAAA
CAGATCGAACACACCCTGAATGAAAAGCGCATCCTGCAAGCTGTCAACTTTCCGTTCCTC
GTCAAACTCGAGTTCTCCTTCAAGGACAACTCAAACTTATACATGGTCATGGAGTACGTG
CCCGGCGGGGAGATGTTCTCACACCTACGGCGGATCGGAAGGTTCAGTGAGCCCCATGCC
CGTTTCTACGCGGCCCAGATCGTCCTGACCTTTGAGTATCTGCACTCGCTGGATCTCATC
TACAGGGACCTGAAGCCGGAGAATCTGCTCATTGACCAGCAGGGCTACATTCAGGTGACA
GACTTCGGTTTCGCCAAGCGCGTGAAGGGCCGCACTTGGACCTTGTGCGGCACCCCTGAG
TACCTGGCCCCTGAGATTATCCTGAGCAAAGGCTACAACAAGGCCGTGGACTGGTGGGCC
CTGGGGGTTCTTATCTATGAAATGGCCGCTGGCTACCCGCCCTTCTTCGCAGACCAGCCC
ATCCAGATCTATGAGAAGATCGTCTCTGGGAAGGTGCGCTTCCCTTCCCACTTCAGCTCT
GACTTGAAGGACCTGCTGCGGAACCTCCTGCAGGTAGATCTCACCAAGCGCTTTGGGAAC
CTCAAGAATGGGGTCAACGATATCAAGAACCACAAGTGGTTTGCCACAACTGACTGGATT
GCCATCTACCAGAGGAAGGTGGAAGCTCCCTTCATACCAAAGTTTAAAGGCCCTGGGGAT
ACGAGTAACTTTGACGACTATGAGGAAGAAGAAATCCGGGTCTCCATCAATGAGAAGTGT
GGCAAGGAGTTTTCTGAGTTTTAG
Chromosome Location
19
Locus
19p13.1
External Identifiers
ResourceLink
UniProtKB IDP17612
UniProtKB Entry NameKAPCA_HUMAN
GenBank Protein ID35479
GenBank Gene IDX07767
HGNC IDHGNC:9380
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01919PentanalexperimentalunknownDetails
DB01940Balanol Analog 2experimentalunknownDetails
DB02155Balanol Analog 8experimentalunknownDetails
DB04098BalanolexperimentalunknownDetails
DB04530S,S-(2-Hydroxyethyl)ThiocysteineexperimentalunknownDetails
DB02482PhosphonothreonineexperimentalunknownDetails
DB04522DexfosfoserineexperimentalunknownDetails
DB06959(2S)-1-(3H-Indol-3-yl)-3-{[5-(6-isoquinolinyl)-3-pyridinyl]oxy}-2-propanamineexperimentalunknownDetails
DB06977(2S)-1-{[5-(1H-Indazol-5-yl)-3-pyridinyl]oxy}-3-(7aH-indol-3-yl)-2-propanamineexperimentalunknownDetails
DB07107(1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINEexperimentalunknownDetails
DB07124(2S)-1-(6H-INDOL-3-YL)-3-{[5-(7H-PYRAZOLO[3,4-C]PYRIDIN-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINEexperimentalunknownDetails
DB07204(1S)-1-(1H-INDOL-3-YLMETHYL)-2-(2-PYRIDIN-4-YL-[1,7]NAPHTYRIDIN-5-YLOXY)-EHYLAMINEexperimentalunknownDetails
DB07235N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDEexperimentalunknownDetails
DB02611Balanol Analog 1experimentalunknownDetails
DB074583-(1H-indol-3-yl)-4-{1-[2-(1-methylpyrrolidin-2-yl)ethyl]-1H-indol-3-yl}-1H-pyrrole-2,5-dioneexperimentalunknownDetails
DB07583(4R,2S)-5'-(4-(4-CHLOROBENZYLOXY)PYRROLIDIN-2-YLMETHANESULFONYL)ISOQUINOLINEexperimentalunknownDetails
DB07854N-METHYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINEexperimentalunknownDetails
DB07855(S)-1-PHENYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINEexperimentalunknownDetails
DB078566-{4-[4-(4-CHLOROPHENYL)PIPERIDIN-4-YL]PHENYL}-9H-PURINEexperimentalunknownDetails
DB07857(2R)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamineexperimentalunknownDetails
DB07858(2S)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamineexperimentalunknownDetails
DB078594-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINEexperimentalunknownDetails
DB07860(2R)-2-(4-CHLOROPHENYL)-2-PHENYLETHANAMINEexperimentalunknownDetails
DB07876(S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINEexperimentalunknownDetails
DB04707HydroxyfasudilexperimentalunknownDetails
DB07947ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDEexperimentalunknownDetails
DB07995N-[2-(4-BROMOCINNAMYLAMINO)ETHYL]-5-ISOQUINOLINE SULFONAMIDEexperimentalunknownDetails
DB079965-(2-methylpiperazine-1-sulfonyl)isoquinolineexperimentalunknownDetails
DB07997N-[2-(METHYLAMINO)ETHYL]-5-ISOQUINOLINESULFONAMIDEexperimentalunknownDetails
DB080702-[4-(3-METHYL-1H-PYRAZOL-4-YL)PHENYL]ETHANAMINEexperimentalunknownDetails
DB08073(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINEexperimentalunknownDetails
DB081133-pyridin-4-yl-1H-indazoleexperimentalunknownDetails
DB081145-benzyl-1,3-thiazol-2-amineexperimentalunknownDetails
DB081481-[4-(4-chlorophenyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamineexperimentalunknownDetails
DB081491-[4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamineexperimentalunknownDetails
DB081504-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-aminiumexperimentalunknownDetails
DB08162FasudilinvestigationalunknownDetails
DB08231Myristic acidexperimentalunknownDetails
DB08568(2S)-1-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}-3-PHENYLPROPAN-2-AMINEexperimentalunknownDetails
DB085693-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.] PYRAZOLEexperimentalunknownDetails
DB033743,5-DiiodotyrosineexperimentalunknownDetails
DB08756(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL) CYCLOHEXANECARBOXAMIDEexperimentalunknownDetails
DB08846Ellagic AcidinvestigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails