PRKACA
entrez
5566
canonical
uniprot
P17612
canonical
ensembl
ENSG00000072062
resolver
ensembl
ENSG00000288516
resolver
ensp
ENSP00000309591
resolver
ensp
ENSP00000466651
resolver
ensp
ENSP00000513361
resolver
enst
ENST00000350356
resolver
genesymbol
PRKACA
resolver
genesymbol_syn
PKACA
resolver
hgnc
HGNC:9380
resolver
uniprot
A0A8V8TL59
resolver
uniprot
A8K8B9
resolver
uniprot
Q32P54
resolver
uniprot
Q9H2Y0
resolver
uniprot
Q9NRB4
resolver
uniprot
Q9NRH9
resolver
uniprot_entry
A0A8V8TL59_HUMAN
resolver
uniprot_entry
A8K8B9_HUMAN
resolver
uniprot_entry
KAPCA_HUMAN
resolver
uniprot_sec
Q32P54
resolver
uniprot_sec
Q9H2Y0
resolver
uniprot_sec
Q9NRB4
resolver
uniprot_sec
Q9NRH9
resolver
activity_regulation
ACTIVITY 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-[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). {ECO:0000269|PubMed:17909264, ECO:0000269|PubMed:18178622, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20137943, ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:20732331}.
uniprot
proteins
amino_acid_sequence
MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWESPAQNTAHLDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFSEF
uniprot
proteins
disease_involvement
DISEASE: Primary pigmented nodular adrenocortical disease 4 (PPNAD4) [MIM:615830]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269|PubMed:24571724, ECO:0000269|PubMed:24700472, ECO:0000269|PubMed:24747643, ECO:0000269|PubMed:24855271}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cardioacrofacial dysplasia 1 (CAFD1) [MIM:619142]: An autosomal dominant disease characterized by dysmorphic facial features, congenital cardiac defects, primarily common atrium or atrioventricular septal defect, and limb anomalies, including short limbs, brachydactyly and postaxial polydactyly. {ECO:0000269|PubMed:33058759}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.11
uniprot
proteins
function
FUNCTION: Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:21852232, PubMed:31112131, PubMed:41652173). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, histone H1.4 (H1-4), PSMC5/RPT6, PJA2, RYR2, RORA, SLC6A6, SOX9, UHRF1 and VASP (PubMed:15178447, PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:41652173). 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 (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). 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 (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). 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+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Acts as a key inhibitor of smoothened signaling pathway by mediating phosphorylation of GLI (GLI1, GLI2 and GLI3) transcription factors in absence of hedgehog (DHH, IHH or SHH) morphogens: GLI phosphorylation promotes their processing and prevents transcriptional activation of smoothened target genes (PubMed:16705181). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (PubMed:36202993, PubMed:39138140). Also inhibits the smoothened signaling pathway in embryonic development by catalyzing phosphorylation of OFD1 in ciliogenesis (PubMed:33934390). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). Phosphorylates AKAP19 (PubMed:27028580). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15178447, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:16705181, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:21852232, ECO:0000269|PubMed:27028580, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:33934390, ECO:0000269|PubMed:36202993, ECO:0000269|PubMed:39138140, ECO:0000269|PubMed:41652173}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}.
uniprot
proteins
mass_dalton
40590
uniprot
proteins
mutagenesis
MUTAGEN 48; /note="K->R: Enhanced basal kinase activity; when associated with Q-96, L-121, A-124, K-182 and A-184."; /evidence="ECO:0000269|PubMed:21774789"; MUTAGEN 96; /note="L->Q: Enhanced basal kinase activity; when associated with R-48, L-121, A-124, K-182 and A-184."; /evidence="ECO:0000269|PubMed:21774789"; MUTAGEN 121; /note="M->L: Enhanced basal kinase activity; when associated with R-48, Q-96, A-124, K-182 and A-184."; /evidence="ECO:0000269|PubMed:21774789"; MUTAGEN 124; /note="V->A: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, K-182 and A-184."; /evidence="ECO:0000269|PubMed:21774789"; MUTAGEN 182; /note="Q->K: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and A-184."; /evidence="ECO:0000269|PubMed:21774789"; MUTAGEN 184; /note="T->A: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and K-182."; /evidence="ECO:0000269|PubMed:21774789"; MUTAGEN 195; /note="R->A: No phosphorylation."; /evidence="ECO:0000269|PubMed:12372837"; MUTAGEN 201; /note="G->A: No phosphorylation."; /evidence="ECO:0000269|PubMed:12372837"; MUTAGEN 202; /note="T->A: No phosphorylation."; /evidence="ECO:0000269|PubMed:12372837"; MUTAGEN 205; /note="Y->A: Loss of allosteric regulation."; /evidence="ECO:0000269|PubMed:18178622
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated. Phosphorylation is enhanced by vitamin K(2) (PubMed:12372837, PubMed:17909264). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (PubMed:16765046, PubMed:20137943, PubMed:20481595, PubMed:20732331, PubMed:21774789, Ref.50). Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (By similarity). {ECO:0000250|UniProtKB:P05132, ECO:0000269|PubMed:12372837, ECO:0000269|PubMed:16765046, ECO:0000269|PubMed:17909264, ECO:0000269|PubMed:20137943, ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:20732331, ECO:0000269|PubMed:21774789, ECO:0000269|Ref.50}.; PTM: Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively. {ECO:0000250|UniProtKB:P05132}.; PTM: When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3. {ECO:0000250|UniProtKB:P05132}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
cAMP subfamily
uniprot
proteins
pubmed
10841548
uniprot
proteins
pubmed
10906071
uniprot
proteins
pubmed
10982398
uniprot
proteins
pubmed
12372837
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15096524
uniprot
proteins
pubmed
15178447
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15642694
uniprot
proteins
pubmed
15905176
uniprot
proteins
pubmed
16387847
uniprot
proteins
pubmed
16705181
uniprot
proteins
pubmed
16765046
uniprot
proteins
pubmed
17333334
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17565987
uniprot
proteins
pubmed
17693412
uniprot
proteins
pubmed
17909264
uniprot
proteins
pubmed
18178622
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18836454
uniprot
proteins
pubmed
19210988
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19949837
uniprot
proteins
pubmed
20137943
uniprot
proteins
pubmed
20356841
uniprot
proteins
pubmed
20481595
uniprot
proteins
pubmed
20732331
uniprot
proteins
pubmed
21085490
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21423175
uniprot
proteins
pubmed
21514275
uniprot
proteins
pubmed
21774789
uniprot
proteins
pubmed
21812984
uniprot
proteins
pubmed
21852232
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24571724
uniprot
proteins
pubmed
24700472
uniprot
proteins
pubmed
24747643
uniprot
proteins
pubmed
24855271
uniprot
proteins
pubmed
25255805
uniprot
proteins
pubmed
25807930
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27028580
uniprot
proteins
pubmed
2843813
uniprot
proteins
pubmed
31112131
uniprot
proteins
pubmed
33058759
uniprot
proteins
pubmed
33934390
uniprot
proteins
pubmed
36202993
uniprot
proteins
pubmed
39138140
uniprot
proteins
pubmed
41652173
uniprot
proteins
sequence_length
351
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175}. Cell membrane {ECO:0000269|PubMed:19210988, ECO:0000269|PubMed:21423175}. Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Nucleus {ECO:0000269|PubMed:21085490}. Mitochondrion {ECO:0000250|UniProtKB:P05132}. Note=Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm. Distributed throughout the cytoplasm in meiotically incompetent oocytes. Associated to mitochondrion as meiotic competence is acquired. Aggregates around the germinal vesicles (GV) at the immature GV stage oocytes (By similarity). Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heat shock (PubMed:21085490). Recruited to the cell membrane through interaction with SMO (By similarity). {ECO:0000250|UniProtKB:P05132, ECO:0000269|PubMed:21085490}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell projection, cilium, flagellum {ECO:0000269|PubMed:10906071}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:P05132}. Note=Expressed in the midpiece region of the sperm flagellum (PubMed:10906071). Colocalizes with MROH2B and TCP11 on the acrosome and tail regions in round spermatids and spermatozoa regardless of the capacitation status of the sperm (By similarity). {ECO:0000250|UniProtKB:P05132, ECO:0000269|PubMed:10906071}.
uniprot
proteins