ID KAPCA_CRIGR Reviewed; 351 AA. AC P25321; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 02-SEP-2026, entry version 167. DE RecName: Full=cAMP-dependent protein kinase catalytic subunit alpha; DE Short=PKA C-alpha; DE EC=2.7.11.11 {ECO:0000250|UniProtKB:P17612}; GN Name=PRKACA; OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; OC Cricetidae; Cricetinae; Cricetulus. OX NCBI_TaxID=10029; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1645343; DOI=10.1016/s0021-9258(18)99208-2; RA Howard P., Day K.H., Kim K.E., Richardson J., Thomas J., Abraham I., RA Fleischmann R.D., Gottesman M.M., Maurer R.A.; RT "Decreased catalytic subunit mRNA levels and altered catalytic subunit mRNA RT structure in a cAMP-resistant Chinese hamster ovary cell line."; RL J. Biol. Chem. 266:10189-10195(1991). CC -!- FUNCTION: Phosphorylates a large number of substrates in the cytoplasm CC and the nucleus. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, histone CC H1.4 (H1-4), PSMC5/RPT6, PJA2, RYR2, RORA, SLC6A6, SOX9, UHRF1 and CC VASP. Regulates the abundance of compartmentalized pools of its CC regulatory subunits through phosphorylation of PJA2 which binds and CC ubiquitinates these subunits, leading to their subsequent proteolysis. CC RORA is activated by phosphorylation. Required for glucose-mediated CC adipogenic differentiation increase and osteogenic differentiation CC inhibition from osteoblasts (By similarity). Involved in chondrogenesis CC by mediating phosphorylation of SOX9 (By similarity). Involved in the CC regulation of platelets in response to thrombin and collagen; maintains CC circulating platelets in a resting state by phosphorylating proteins in CC numerous platelet inhibitory pathways when in complex with NF-kappa-B CC (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and CC collagen disrupt these complexes and free active PRKACA stimulates CC platelets and leads to platelet aggregation by phosphorylating VASP. CC Prevents the antiproliferative and anti-invasive effects of alpha- CC difluoromethylornithine in breast cancer cells when activated. RYR2 CC channel activity is potentiated by phosphorylation in presence of CC luminal Ca(2+), leading to reduced amplitude and increased frequency of CC store overload-induced Ca(2+) release (SOICR) characterized by an CC increased rate of Ca(2+) release and propagation velocity of CC spontaneous Ca(2+) waves, despite reduced wave amplitude and resting CC cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates CC proteasome. Negatively regulates tight junctions (TJs) in ovarian CC cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes CC NF-kappa-B p50-p50 DNA binding (By similarity). Acts as a key inhibitor CC of smoothened signaling pathway by mediating phosphorylation of GLI CC (GLI1, GLI2 and GLI3) transcription factors in absence of hedgehog CC (DHH, IHH or SHH) morphogens: GLI phosphorylation promotes their CC processing and prevents transcriptional activation of smoothened target CC genes (By similarity). GLI transcription factor phosphorylation is CC inhibited by interaction of PRKACA with SMO which sequesters PRKACA at CC the cell membrane (By similarity). Also inhibits the smoothened CC signaling pathway in embryonic development by catalyzing CC phosphorylation of OFD1 in ciliogenesis (By similarity). Prevents CC meiosis resumption in prophase-arrested oocytes via CDC25B inactivation CC by phosphorylation (By similarity). May also regulate rapid eye CC movement (REM) sleep in the pedunculopontine tegmental (PPT) (By CC similarity). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; CC this phosphorylation promotes HSF1 nuclear localization and CC transcriptional activity upon heat shock. Acts as a negative regulator CC of mTORC1 by mediating phosphorylation of RPTOR. Phosphorylates AKAP19 CC (By similarity). {ECO:0000250|UniProtKB:P05132, CC ECO:0000250|UniProtKB:P17612, ECO:0000250|UniProtKB:P27791}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.11; CC Evidence={ECO:0000250|UniProtKB:P17612}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.11; CC Evidence={ECO:0000250|UniProtKB:P17612}; CC -!- ACTIVITY REGULATION: Allosterically activated by various compounds, CC including ATP. Activated by cAMP; the nucleotide acts as a dynamic and CC allosteric activator by coupling the two lobes of apo PKA, enhancing CC the enzyme dynamics synchronously and priming it for catalysis. CC -!- SUBUNIT: A number of inactive tetrameric holoenzymes are produced by CC the combination of homo- or heterodimers of the different regulatory CC subunits associated with two catalytic subunits. cAMP causes the CC dissociation of the inactive holoenzyme into a dimer of regulatory CC subunits bound to four cAMP and two free monomeric catalytic subunits. CC Activates cAMP-sensitive PKAI and PKAII holoenzymes by interacting with CC regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, CC respectively. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; CC these interactions are disrupted by thrombin and collagen. Binds to CC ABL1 in spermatozoa and with CDC25B in oocytes (By similarity). CC Interacts with APOBEC3G and AICDA (By similarity). Interacts with CC RAB13; downstream effector of RAB13 involved in tight junction assembly CC (By similarity). Found in a complex at least composed of MROH2B, PRKACA CC and TCP11 (By similarity). Interacts with MROH2B (By similarity). CC Interacts with HSF1 (By similarity). Interacts with TCP11 (By CC similarity). Interacts with TBC1D31; in the regulation of OFD1 (By CC similarity). Interacts in free form with SMO (via C-terminus); the CC interaction leads to sequestration of PRKACA at the membrane, CC preventing PRKACA-mediated phosphorylation of GLI transcription factors CC (By similarity). {ECO:0000250|UniProtKB:P05132, CC ECO:0000250|UniProtKB:P17612}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P17612}. Cell CC membrane {ECO:0000250|UniProtKB:P17612}. Membrane CC {ECO:0000250|UniProtKB:P17612}; Lipid-anchor CC {ECO:0000250|UniProtKB:P17612}. Nucleus {ECO:0000250|UniProtKB:P17612}. CC Mitochondrion {ECO:0000250|UniProtKB:P05132}. Note=Translocates into CC the nucleus (monomeric catalytic subunit). The inactive holoenzyme is CC found in the cytoplasm. Distributed throughout the cytoplasm in CC meiotically incompetent oocytes. Associated to mitochondrion as meiotic CC competence is acquired. Aggregates around the germinal vesicles (GV) at CC the immature GV stage oocytes (By similarity). Colocalizes with HSF1 in CC nuclear stress bodies (nSBs) upon heat shock (By similarity). Recruited CC to the cell membrane through interaction with SMO (By similarity). CC {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P17612}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in mammalian tissues. CC -!- PTM: Autophosphorylated. Phosphorylation is enhanced by vitamin K(2). CC Phosphorylated on threonine and serine residues. Phosphorylation on CC Thr-198 is required for full activity (By similarity). Phosphorylated CC at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this CC increases catalytic efficiency (By similarity). CC {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P17612}. CC -!- PTM: Asn-3 is partially deaminated to Asp-3 giving rise to 2 major CC isoelectric variants, called CB and CA respectively. CC {ECO:0000250|UniProtKB:P05132}. CC -!- PTM: When myristoylated, Ser-11 is autophosphorylated probably in CC conjunction with deamidation of Asn-3. {ECO:0000250|UniProtKB:P05132}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. cAMP subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M63311; AAA37010.1; -; mRNA. DR PIR; B40384; OKHYCA. DR RefSeq; XP_016830834.2; XM_016975345.3. DR RefSeq; XP_027261982.1; XM_027406181.2. DR PDB; 4WIH; X-ray; 1.14 A; A=1-351. DR PDB; 5LCP; X-ray; 1.43 A; A=1-351. DR PDB; 5LCQ; X-ray; 1.42 A; A=1-351. DR PDB; 5LCR; X-ray; 1.56 A; A=1-351. DR PDB; 5LCT; X-ray; 1.61 A; A=1-351. DR PDB; 5LCU; X-ray; 1.58 A; A=1-351. DR PDB; 5M0B; X-ray; 1.51 A; A=1-351. DR PDB; 5M0C; X-ray; 1.73 A; A=1-351. DR PDB; 5M0L; X-ray; 1.47 A; A=1-351. DR PDB; 5M0U; X-ray; 1.67 A; A=1-351. DR PDB; 5M6V; X-ray; 1.42 A; A=1-351. DR PDB; 5M6Y; X-ray; 1.37 A; A=1-351. DR PDB; 5M71; X-ray; 1.49 A; A=1-351. DR PDB; 5M75; X-ray; 1.54 A; A=1-351. DR PDB; 5MHI; X-ray; 1.49 A; A=1-351. DR PDB; 5N1D; X-ray; 1.61 A; A=1-351. DR PDB; 5N1E; X-ray; 1.53 A; A=1-351. DR PDB; 5N1F; X-ray; 1.12 A; A=1-351. DR PDB; 5N1G; X-ray; 1.14 A; A=1-351. DR PDB; 5N1H; X-ray; 1.18 A; A=1-351. DR PDB; 5N1K; X-ray; 1.80 A; A=1-351. DR PDB; 5N1L; X-ray; 1.49 A; A=1-351. DR PDB; 5N1M; X-ray; 1.44 A; A=1-351. DR PDB; 5N1N; X-ray; 1.41 A; A=1-351. DR PDB; 5N1O; X-ray; 1.80 A; A=1-351. DR PDB; 5N32; X-ray; 1.83 A; A=1-351. DR PDB; 5N33; X-ray; 1.43 A; A=1-351. DR PDB; 5N36; X-ray; 1.58 A; A=1-351. DR PDB; 5N37; X-ray; 1.59 A; A=1-351. DR PDB; 5N39; X-ray; 1.45 A; A=1-351. DR PDB; 5N3A; X-ray; 1.40 A; A=1-351. DR PDB; 5N3B; X-ray; 1.64 A; A=1-351. DR PDB; 5N3C; X-ray; 1.77 A; A=1-351. DR PDB; 5N3D; X-ray; 1.77 A; A=1-351. DR PDB; 5N3E; X-ray; 1.53 A; A=1-351. DR PDB; 5N3F; X-ray; 1.68 A; A=1-351. DR PDB; 5N3G; X-ray; 1.16 A; A=1-351. DR PDB; 5N3H; X-ray; 1.36 A; A=1-351. DR PDB; 5N3I; X-ray; 1.14 A; A=1-351. DR PDB; 5N3J; X-ray; 1.12 A; A=1-351. DR PDB; 5N3K; X-ray; 1.33 A; A=1-351. DR PDB; 5N3L; X-ray; 1.38 A; A=1-351. DR PDB; 5N3M; X-ray; 1.23 A; A=1-351. DR PDB; 5N3N; X-ray; 1.22 A; A=1-351. DR PDB; 5N3O; X-ray; 1.32 A; A=1-351. DR PDB; 5N3P; X-ray; 1.58 A; A=1-351. DR PDB; 5N3Q; X-ray; 1.31 A; A=1-351. DR PDB; 5N3R; X-ray; 1.36 A; A=1-351. DR PDB; 5N3S; X-ray; 1.14 A; A=1-351. DR PDB; 5N3T; X-ray; 1.21 A; A=1-351. DR PDB; 5N7P; X-ray; 1.50 A; A=1-351. DR PDB; 5N7U; X-ray; 1.37 A; A=1-351. DR PDB; 5NTJ; X-ray; 1.56 A; A=1-351. DR PDB; 5NW8; X-ray; 2.09 A; A=1-351. DR PDB; 5O0E; X-ray; 1.50 A; A=1-351. DR PDB; 5O5M; X-ray; 1.58 A; A=1-351. DR PDB; 5OK3; X-ray; 1.59 A; A=1-351. DR PDB; 5OL3; X-ray; 1.58 A; A=1-351. DR PDB; 5OT3; X-ray; 2.04 A; A=1-351. DR PDB; 5OTG; X-ray; 1.73 A; A=1-351. DR PDB; 5OUA; X-ray; 1.67 A; A=1-351. DR PDB; 5OUC; X-ray; 1.46 A; A=1-351. DR PDB; 5OUS; X-ray; 2.21 A; A=1-351. DR PDB; 6EGW; X-ray; 1.74 A; A=1-351. DR PDB; 6EH0; X-ray; 1.49 A; A=1-351. DR PDB; 6EH2; X-ray; 1.76 A; A=1-351. DR PDB; 6EH3; X-ray; 1.95 A; A=1-351. DR PDB; 6EM2; X-ray; 1.30 A; A=1-351. DR PDB; 6EM6; X-ray; 1.64 A; A=1-351. DR PDB; 6EM7; X-ray; 1.24 A; A=1-351. DR PDB; 6EMA; X-ray; 1.88 A; A=1-351. DR PDB; 6ERT; X-ray; 1.80 A; A=1-351. DR PDB; 6ERU; X-ray; 2.15 A; A=1-351. DR PDB; 6ERV; X-ray; 2.06 A; A=1-351. DR PDB; 6ERW; X-ray; 1.89 A; A=1-351. DR PDB; 6ESA; X-ray; 1.31 A; A=1-351. DR PDB; 6F14; X-ray; 1.87 A; A=1-351. DR PDB; 6I2A; X-ray; 1.75 A; A=1-351. DR PDB; 6I2B; X-ray; 1.97 A; A=1-351. DR PDB; 6I2C; X-ray; 1.82 A; A=1-351. DR PDB; 6I2D; X-ray; 1.91 A; A=1-351. DR PDB; 6I2H; X-ray; 1.68 A; A=1-351. DR PDB; 6SNN; X-ray; 1.82 A; A=1-351. DR PDB; 6SNX; X-ray; 1.40 A; A=1-351. DR PDB; 6SOX; X-ray; 1.38 A; A=1-351. DR PDB; 6SPM; X-ray; 1.37 A; A=1-351. DR PDB; 6SPS; X-ray; 1.65 A; A=1-351. DR PDB; 6SPU; X-ray; 1.39 A; A=1-351. DR PDB; 6SPY; X-ray; 1.60 A; A=1-351. DR PDB; 6SQ1; X-ray; 1.49 A; A=1-351. DR PDB; 6Y05; X-ray; 1.70 A; A=1-351. DR PDB; 6Y0B; X-ray; 1.71 A; A=1-351. DR PDB; 6Y2O; X-ray; 2.01 A; A=1-351. DR PDB; 6Y2U; X-ray; 1.93 A; A=1-351. DR PDB; 6Y89; X-ray; 1.56 A; A=1-351. DR PDB; 6Y8C; X-ray; 1.76 A; A=1-351. DR PDB; 6YNA; X-ray; 1.47 A; A=1-351. DR PDB; 6YNB; X-ray; 1.72 A; A=1-351. DR PDB; 6YNC; X-ray; 1.40 A; A=1-351. DR PDB; 6YNR; X-ray; 1.90 A; A=1-351. DR PDB; 6YNT; X-ray; 1.52 A; A=1-351. DR PDB; 6YOT; X-ray; 1.96 A; A=1-351. DR PDB; 6YOU; X-ray; 1.73 A; A=1-351. DR PDB; 6YPP; X-ray; 1.75 A; A=1-351. DR PDB; 6YPS; X-ray; 1.35 A; A=1-351. DR PDB; 6YQI; X-ray; 1.42 A; A=1-351. DR PDB; 6YQJ; X-ray; 1.58 A; A=1-351. DR PDB; 6YQK; X-ray; 1.67 A; A=1-351. DR PDB; 6Z08; X-ray; 1.49 A; A=1-351. DR PDB; 6Z44; X-ray; 1.38 A; A=1-351. DR PDB; 6ZN0; X-ray; 1.59 A; A=1-351. DR PDB; 7AXT; X-ray; 1.86 A; A=1-351. DR PDB; 7AXV; X-ray; 1.79 A; A=1-351. DR PDB; 7AXW; X-ray; 1.69 A; A=1-351. DR PDB; 7BAQ; X-ray; 1.54 A; A=1-351. DR PDB; 7BAR; X-ray; 1.37 A; A=1-351. DR PDB; 7BB0; X-ray; 1.75 A; A=1-351. DR PDB; 7PID; X-ray; 1.50 A; A=1-351. DR PDB; 7PIE; X-ray; 1.43 A; A=1-351. DR PDB; 7PIF; X-ray; 1.40 A; A=1-351. DR PDB; 7PIG; X-ray; 1.55 A; A=1-351. DR PDB; 7PIH; X-ray; 1.37 A; A=1-351. DR PDB; 7PNS; X-ray; 1.85 A; A=1-351. DR PDB; 9RDU; X-ray; 1.42 A; A=1-351. DR PDB; 9RDV; X-ray; 1.32 A; A=1-351. DR PDB; 9RDW; X-ray; 1.44 A; A=1-351. DR PDB; 9RDX; X-ray; 1.50 A; A=1-351. DR PDB; 9RDY; X-ray; 1.50 A; A=1-351. DR PDB; 9RDZ; X-ray; 1.64 A; A=1-351. DR PDB; 9RE0; X-ray; 1.58 A; A=1-351. DR PDB; 9RE1; X-ray; 1.41 A; A=1-351. DR PDB; 9RE2; X-ray; 1.68 A; A=1-351. DR PDB; 9RE3; X-ray; 1.57 A; A=1-351. DR PDB; 9RE4; X-ray; 1.47 A; A=1-351. DR PDB; 9RE5; X-ray; 1.70 A; A=1-351. DR PDB; 9RE6; X-ray; 1.45 A; A=1-351. DR PDB; 9RE7; X-ray; 1.46 A; A=1-351. DR PDB; 9RE8; X-ray; 1.50 A; A=1-351. DR PDB; 9RE9; X-ray; 1.41 A; A=1-351. DR PDB; 9REA; X-ray; 1.52 A; A=1-351. DR PDB; 9REB; X-ray; 1.39 A; A=1-351. DR PDB; 9REC; X-ray; 1.20 A; A=1-351. DR PDB; 9RED; X-ray; 1.31 A; A=1-351. DR PDB; 9REE; X-ray; 1.34 A; A=1-351. DR PDB; 9REF; X-ray; 1.42 A; A=1-351. DR PDB; 9REG; X-ray; 1.35 A; A=1-351. DR PDB; 9REH; X-ray; 1.33 A; A=1-351. DR PDB; 9REI; X-ray; 1.42 A; A=1-351. DR PDB; 9REJ; X-ray; 1.40 A; A=1-351. DR PDB; 9REK; X-ray; 1.38 A; A=1-351. DR PDB; 9REL; X-ray; 1.42 A; A=1-351. DR PDB; 9REM; X-ray; 1.43 A; A=1-351. DR PDB; 9REN; X-ray; 1.38 A; A=1-351. DR PDB; 9REO; X-ray; 1.45 A; A=1-351. DR PDB; 9REP; X-ray; 1.44 A; A=1-351. DR PDB; 9REQ; X-ray; 1.50 A; A=1-351. DR PDB; 9RER; X-ray; 1.45 A; A=1-351. DR PDB; 9RES; X-ray; 1.50 A; A=1-351. DR PDB; 9RET; X-ray; 1.75 A; A=1-351. DR AlphaFoldDB; P25321; -. DR BMRB; P25321; -. DR MDRepo; P25321; -. DR SMR; P25321; -. DR ChEMBL; CHEMBL4295732; -. DR Ensembl; ENSCGRT00001021270; ENSCGRP00001017026; ENSCGRG00001017184. DR Ensembl; ENSCGRT00015025970; ENSCGRP00015021134; ENSCGRG00015016064. DR GeneID; 100768997; -. DR KEGG; cge:100768997; -. DR CTD; 5566; -. DR eggNOG; KOG0616; Eukaryota. DR GeneTree; ENSGT00940000162186; -. DR OrthoDB; 63267at2759; -. DR BRENDA; 2.7.11.11; 1309. DR EvolutionaryTrace; P25321; -. DR Proteomes; UP001108280; Chromosome 3. DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB. DR GO; GO:0005930; C:axoneme; IEA:Ensembl. DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IEA:Ensembl. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0097546; C:ciliary base; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005811; C:lipid droplet; IEA:Ensembl. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0044853; C:plasma membrane raft; IEA:Ensembl. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:Ensembl. DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; ISS:UniProtKB. DR GO; GO:0140198; F:histone H1-4S35 kinase activity; ISS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl. DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IEA:Ensembl. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:Ensembl. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEA:Ensembl. DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB. DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; IEA:Ensembl. DR GO; GO:0006397; P:mRNA processing; IEA:Ensembl. DR GO; GO:1904539; P:negative regulation of glycolytic process through fructose-6-phosphate; IEA:Ensembl. DR GO; GO:0120186; P:negative regulation of protein localization to chromatin; IEA:Ensembl. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB. DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IEA:Ensembl. DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl. DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IEA:Ensembl. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IEA:Ensembl. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IEA:Ensembl. DR GO; GO:0045667; P:regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Ensembl. DR GO; GO:0048240; P:sperm capacitation; IEA:Ensembl. DR CDD; cd14209; STKc_PKA; 1. DR FunFam; 3.30.200.20:FF:000005; cAMP-dependent protein kinase catalytic subunit; 1. DR FunFam; 1.10.510.10:FF:000005; cAMP-dependent protein kinase catalytic subunit alpha; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR044109; STKc_PKA. DR PANTHER; PTHR24353:SF82; CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT ALPHA; 1. DR PANTHER; PTHR24353; CYCLIC NUCLEOTIDE-DEPENDENT PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51285; AGC_KINASE_CTER; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PDBsum; 4WIH; -. DR PDBsum; 5LCP; -. DR PDBsum; 5LCQ; -. DR PDBsum; 5LCR; -. DR PDBsum; 5LCT; -. DR PDBsum; 5LCU; -. DR PDBsum; 5M0B; -. DR PDBsum; 5M0C; -. DR PDBsum; 5M0L; -. DR PDBsum; 5M0U; -. DR PDBsum; 5M6V; -. DR PDBsum; 5M6Y; -. DR PDBsum; 5M71; -. DR PDBsum; 5M75; -. DR PDBsum; 5MHI; -. DR PDBsum; 5N1D; -. DR PDBsum; 5N1E; -. DR PDBsum; 5N1F; -. DR PDBsum; 5N1G; -. DR PDBsum; 5N1H; -. DR PDBsum; 5N1K; -. DR PDBsum; 5N1L; -. DR PDBsum; 5N1M; -. DR PDBsum; 5N1N; -. DR PDBsum; 5N1O; -. DR PDBsum; 5N32; -. DR PDBsum; 5N33; -. DR PDBsum; 5N36; -. DR PDBsum; 5N37; -. DR PDBsum; 5N39; -. DR PDBsum; 5N3A; -. DR PDBsum; 5N3B; -. DR PDBsum; 5N3C; -. DR PDBsum; 5N3D; -. DR PDBsum; 5N3E; -. DR PDBsum; 5N3F; -. DR PDBsum; 5N3G; -. DR PDBsum; 5N3H; -. DR PDBsum; 5N3I; -. DR PDBsum; 5N3J; -. DR PDBsum; 5N3K; -. DR PDBsum; 5N3L; -. DR PDBsum; 5N3M; -. DR PDBsum; 5N3N; -. DR PDBsum; 5N3O; -. DR PDBsum; 5N3P; -. DR PDBsum; 5N3Q; -. DR PDBsum; 5N3R; -. DR PDBsum; 5N3S; -. DR PDBsum; 5N3T; -. DR PDBsum; 5N7P; -. DR PDBsum; 5N7U; -. DR PDBsum; 5NTJ; -. DR PDBsum; 5NW8; -. DR PDBsum; 5O0E; -. DR PDBsum; 5O5M; -. DR PDBsum; 5OK3; -. DR PDBsum; 5OL3; -. DR PDBsum; 5OT3; -. DR PDBsum; 5OTG; -. DR PDBsum; 5OUA; -. DR PDBsum; 5OUC; -. DR PDBsum; 5OUS; -. DR PDBsum; 6EGW; -. DR PDBsum; 6EH0; -. DR PDBsum; 6EH2; -. DR PDBsum; 6EH3; -. DR PDBsum; 6EM2; -. DR PDBsum; 6EM6; -. DR PDBsum; 6EM7; -. DR PDBsum; 6EMA; -. DR PDBsum; 6ERT; -. DR PDBsum; 6ERU; -. DR PDBsum; 6ERV; -. DR PDBsum; 6ERW; -. DR PDBsum; 6ESA; -. DR PDBsum; 6F14; -. DR PDBsum; 6I2A; -. DR PDBsum; 6I2B; -. DR PDBsum; 6I2C; -. DR PDBsum; 6I2D; -. DR PDBsum; 6I2H; -. DR PDBsum; 6SNN; -. DR PDBsum; 6SNX; -. DR PDBsum; 6SOX; -. DR PDBsum; 6SPM; -. DR PDBsum; 6SPS; -. DR PDBsum; 6SPU; -. DR PDBsum; 6SPY; -. DR PDBsum; 6SQ1; -. DR PDBsum; 6Y05; -. DR PDBsum; 6Y0B; -. DR PDBsum; 6Y2O; -. DR PDBsum; 6Y2U; -. DR PDBsum; 6Y89; -. DR PDBsum; 6Y8C; -. DR PDBsum; 6YNA; -. DR PDBsum; 6YNB; -. DR PDBsum; 6YNC; -. DR PDBsum; 6YNR; -. DR PDBsum; 6YNT; -. DR PDBsum; 6YOT; -. DR PDBsum; 6YOU; -. DR PDBsum; 6YPP; -. DR PDBsum; 6YPS; -. DR PDBsum; 6YQI; -. DR PDBsum; 6YQJ; -. DR PDBsum; 6YQK; -. DR PDBsum; 6Z08; -. DR PDBsum; 6Z44; -. DR PDBsum; 6ZN0; -. DR PDBsum; 7AXT; -. DR PDBsum; 7AXV; -. DR PDBsum; 7AXW; -. DR PDBsum; 7BAQ; -. DR PDBsum; 7BAR; -. DR PDBsum; 7BB0; -. DR PDBsum; 7PID; -. DR PDBsum; 7PIE; -. DR PDBsum; 7PIF; -. DR PDBsum; 7PIG; -. DR PDBsum; 7PIH; -. DR PDBsum; 7PNS; -. DR PDBsum; 9RDU; -. DR PDBsum; 9RDV; -. DR PDBsum; 9RDW; -. DR PDBsum; 9RDX; -. DR PDBsum; 9RDY; -. DR PDBsum; 9RDZ; -. DR PDBsum; 9RE0; -. DR PDBsum; 9RE1; -. DR PDBsum; 9RE2; -. DR PDBsum; 9RE3; -. DR PDBsum; 9RE4; -. DR PDBsum; 9RE5; -. DR PDBsum; 9RE6; -. DR PDBsum; 9RE7; -. DR PDBsum; 9RE8; -. DR PDBsum; 9RE9; -. DR PDBsum; 9REA; -. DR PDBsum; 9REB; -. DR PDBsum; 9REC; -. DR PDBsum; 9RED; -. DR PDBsum; 9REE; -. DR PDBsum; 9REF; -. DR PDBsum; 9REG; -. DR PDBsum; 9REH; -. DR PDBsum; 9REI; -. DR PDBsum; 9REJ; -. DR PDBsum; 9REK; -. DR PDBsum; 9REL; -. DR PDBsum; 9REM; -. DR PDBsum; 9REN; -. DR PDBsum; 9REO; -. DR PDBsum; 9REP; -. DR PDBsum; 9REQ; -. DR PDBsum; 9RER; -. DR PDBsum; 9RES; -. DR PDBsum; 9RET; -. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; cAMP; Cell membrane; Cytoplasm; Kinase; KW Lipoprotein; Membrane; Mitochondrion; Myristate; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P00517" FT CHAIN 2..351 FT /note="cAMP-dependent protein kinase catalytic subunit FT alpha" FT /id="PRO_0000086051" FT DOMAIN 44..298 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 299..351 FT /note="AGC-kinase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618" FT ACT_SITE 167 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 50..58 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 73 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 122..128 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 169..172 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 3 FT /note="Deamidated asparagine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 11 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 49 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P17612" FT MOD_RES 140 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 196 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P17612" FT MOD_RES 198 FT /note="Phosphothreonine; by PDPK1" FT /evidence="ECO:0000250|UniProtKB:P00517" FT MOD_RES 331 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00517" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250|UniProtKB:P17612" FT HELIX 14..32 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 34..36 FT /evidence="ECO:0007829|PDB:4WIH" FT HELIX 41..43 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 44..52 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 54..63 FT /evidence="ECO:0007829|PDB:5N1F" FT TURN 64..66 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 69..76 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 77..82 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 86..98 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 107..112 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 114..122 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 129..136 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 141..160 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 173..175 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 208..211 FT /evidence="ECO:0007829|PDB:5N1F" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:5LCQ" FT HELIX 219..234 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 244..253 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 257..259 FT /evidence="ECO:0007829|PDB:5N3R" FT HELIX 264..273 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:5N1F" FT TURN 286..289 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 290..293 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 303..307 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:5N1F" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:5OUS" FT HELIX 332..335 FT /evidence="ECO:0007829|PDB:5LCU" FT HELIX 337..339 FT /evidence="ECO:0007829|PDB:6Y2U" FT TURN 345..350 FT /evidence="ECO:0007829|PDB:5N1F" SQ SEQUENCE 351 AA; 40620 MW; 84333CD0B439F356 CRC64; MGNAAAAKKG SEQESVKEFL AKAKEEFLKK WESPSQNTAQ LDHFDRIKTL GTGSFGRVML VKHKETGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE F //