Prkaca
entrez
18747
canonical
uniprot
P05132
canonical
ensembl
ENSMUSG00000005469
resolver
ensp
ENSMUSP00000005606
resolver
ensp
ENSMUSP00000147256
resolver
genesymbol
Prkaca
resolver
genesymbol_syn
Pkaca
resolver
uniprot
Q9JID0
resolver
uniprot_entry
KAPCA_MOUSE
resolver
uniprot_sec
Q9JID0
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. {ECO:0000269|PubMed:20890288}.
uniprot
proteins
amino_acid_sequence
MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWETPSQNTAQLDQFDRIKTLGTGSFGRVMLVKHKESGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVAGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFTEF
uniprot
proteins
ec_number
2.7.11.11
uniprot
proteins
function
FUNCTION: Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, histone H1.4 (H1-4), PSMC5/RPT6, PJA2, RYR2, RORA, SLC6A6, SOX9, UHRF1 and VASP (PubMed:10805756, PubMed:19223768). 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 (By similarity). RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity). Involved in chondrogenesis by mediating phosphorylation of SOX9 (PubMed:10805756). 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. 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. 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:33886552). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (PubMed:33886552, PubMed:39138140). Also inhibits the smoothened signaling pathway in embryonic development by catalyzing phosphorylation of OFD1 in ciliogenesis (By similarity). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (PubMed:19223768). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (By similarity). Phosphorylates AKAP19 (By similarity). {ECO:0000250|UniProtKB:P17612, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:19223768, ECO:0000269|PubMed:33886552, ECO:0000269|PubMed:39138140}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000269|PubMed:15340140, ECO:0000269|PubMed:19560455}.
uniprot
proteins
mass_dalton
40571
uniprot
proteins
mutagenesis
MUTAGEN 73; /note="K->H: Reduced interaction with SMO."; /evidence="ECO:0000269|PubMed:33886552"; MUTAGEN 88; /note="H->Q: Does not affect interaction with SMO; when associated with R-197."; /evidence="ECO:0000269|PubMed:33886552"; MUTAGEN 197; /note="W->R: Does not affect interaction with SMO; when associated with Q-88."; /evidence="ECO:0000269|PubMed:33886552"; MUTAGEN 198; /note="T->D: No phosphorylation by PDPK1."; MUTAGEN 206; /note="L->R: Reduced interaction with SMO."; /evidence="ECO:0000269|PubMed:33886552"; MUTAGEN 286; /note="K->P: Impaired inhibition by the R-subunit."; /evidence="ECO:0000269|PubMed:19122195"; MUTAGEN 328; /note="F->A: Reduced catalytic activity and impaired inhibition by the R-subunit."; /evidence="ECO:0000269|PubMed:19122195
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated; phosphorylation is enhanced by vitamin K(2) (By similarity). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (PubMed:8395513, PubMed:9707564). Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (PubMed:21866565). {ECO:0000250|UniProtKB:P17612, ECO:0000269|PubMed:21866565, ECO:0000269|PubMed:8395513, ECO:0000269|PubMed:9707564}.; PTM: Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively. {ECO:0000269|PubMed:11141074}.; PTM: When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3. {ECO:0000269|PubMed:11141074, ECO:0000269|PubMed:8395513}.
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
10805756
uniprot
proteins
pubmed
10982398
uniprot
proteins
pubmed
11141074
uniprot
proteins
pubmed
11875122
uniprot
proteins
pubmed
15340140
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16611981
uniprot
proteins
pubmed
17889648
uniprot
proteins
pubmed
17932298
uniprot
proteins
pubmed
18367160
uniprot
proteins
pubmed
1862342
uniprot
proteins
pubmed
19122195
uniprot
proteins
pubmed
19223768
uniprot
proteins
pubmed
19560455
uniprot
proteins
pubmed
19748511
uniprot
proteins
pubmed
20890288
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21866565
uniprot
proteins
pubmed
22323819
uniprot
proteins
pubmed
27105888
uniprot
proteins
pubmed
2833513
uniprot
proteins
pubmed
33886552
uniprot
proteins
pubmed
3456589
uniprot
proteins
pubmed
39138140
uniprot
proteins
pubmed
8395513
uniprot
proteins
pubmed
8443157
uniprot
proteins
pubmed
9109651
uniprot
proteins
pubmed
9261084
uniprot
proteins
pubmed
9707564
uniprot
proteins
sequence_length
351
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18367160}. Cell membrane {ECO:0000269|PubMed:33886552}. Nucleus {ECO:0000250|UniProtKB:P17612}. Mitochondrion {ECO:0000269|PubMed:18367160}. Membrane {ECO:0000250|UniProtKB:P17612}; Lipid-anchor {ECO:0000250|UniProtKB:P17612}. Note=Translocates into the nucleus (monomeric catalytic subunit) (By similarity). 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. Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heat shock (By similarity). Recruited to the cell membrane through interaction with SMO (PubMed:33886552). {ECO:0000250|UniProtKB:P17612, ECO:0000269|PubMed:33886552}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell projection, cilium, flagellum {ECO:0000269|PubMed:27105888}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000269|PubMed:27105888}. Note=Expressed in the midpiece region of the sperm flagellum (By similarity). Colocalizes with MROH2B and TCP11 on the acrosome and tail regions in round spermatids and spermatozoa regardless of the capacitation status of the sperm (PubMed:27105888). {ECO:0000250, ECO:0000269|PubMed:27105888}.
uniprot
proteins