P25321 · KAPCA_CRIGR
- ProteincAMP-dependent protein kinase catalytic subunit alpha
- GenePRKACA
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids351 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity).
Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (By similarity).
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. 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 (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. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca2+, leading to reduced amplitude and increased frequency of store overload-induced Ca2+ release (SOICR) characterized by an increased rate of Ca2+ release and propagation velocity of spontaneous Ca2+ waves, despite reduced wave amplitude and resting cytosolic Ca2+. 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. Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity).
GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity).
Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (By similarity).
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. 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 CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (By similarity).
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. 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 (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. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca2+, leading to reduced amplitude and increased frequency of store overload-induced Ca2+ release (SOICR) characterized by an increased rate of Ca2+ release and propagation velocity of spontaneous Ca2+ waves, despite reduced wave amplitude and resting cytosolic Ca2+. 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. Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity).
GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity).
Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (By similarity).
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. 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).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
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.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namecAMP-dependent protein kinase catalytic subunit alpha
- EC number
- Short namesPKA C-alpha
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Cricetidae > Cricetinae > Cricetulus
Accessions
- Primary accessionP25321
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Lipid-anchor
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 (By similarity).
Recruited to the cell membrane through interaction with SMO (By similarity).
Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heat shock (By similarity).
Recruited to the cell membrane through interaction with SMO (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Lipidation | 2 | N-myristoyl glycine | ||||
Sequence: G | ||||||
Chain | PRO_0000086051 | 2-351 | cAMP-dependent protein kinase catalytic subunit alpha | |||
Sequence: GNAAAAKKGSEQESVKEFLAKAKEEFLKKWESPSQNTAQLDHFDRIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFTEF | ||||||
Modified residue | 3 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 11 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 49 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 140 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 196 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 198 | Phosphothreonine; by PDPK1 | ||||
Sequence: T | ||||||
Modified residue | 331 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 339 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autophosphorylated. Phosphorylation is enhanced by vitamin K2. Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (By similarity).
Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (By similarity).
Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (By similarity).
Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively.
When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3.
Keywords
- PTM
Proteomic databases
Expression
Tissue specificity
Ubiquitously expressed in mammalian tissues.
Interaction
Subunit
A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Activates cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes (By similarity).
Interacts with APOBEC3G and AICDA (By similarity).
Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly (By similarity).
Found in a complex at least composed of MROH2B, PRKACA and TCP11 (By similarity).
Interacts with MROH2B (By similarity).
Interacts with HSF1 (By similarity).
Interacts with TCP11 (By similarity).
Interacts with TBC1D31; in the regulation of OFD1 (By similarity).
Interacts in free form with SMO (via C-terminus); the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors (By similarity).
Interacts with APOBEC3G and AICDA (By similarity).
Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly (By similarity).
Found in a complex at least composed of MROH2B, PRKACA and TCP11 (By similarity).
Interacts with MROH2B (By similarity).
Interacts with HSF1 (By similarity).
Interacts with TCP11 (By similarity).
Interacts with TBC1D31; in the regulation of OFD1 (By similarity).
Interacts in free form with SMO (via C-terminus); the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors (By similarity).
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 44-298 | Protein kinase | ||||
Sequence: FDRIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWF | ||||||
Domain | 299-351 | AGC-kinase C-terminal | ||||
Sequence: ATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFTEF |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length351
- Mass (Da)40,620
- Last updated2007-01-23 v2
- Checksum84333CD0B439F356
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M63311 EMBL· GenBank· DDBJ | AAA37010.1 EMBL· GenBank· DDBJ | mRNA |