ID KAPCA_CANLF Reviewed; 350 AA.
AC Q8MJ44;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 146.
DE RecName: Full=cAMP-dependent protein kinase catalytic subunit alpha;
DE Short=PKA C-alpha;
DE EC=2.7.11.11;
GN Name=PRKACA;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Mishra S., Rastogi S., Tiwari N., Sabbah H.N., Gupta R.C.;
RT "Cloning and sequencing of protein kinase A alpha from dog heart.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INTERACTION WITH RAB13.
RX PubMed=15096524; DOI=10.1083/jcb.200312118;
RA Koehler K., Louvard D., Zahraoui A.;
RT "Rab13 regulates PKA signaling during tight junction assembly.";
RL J. Cell Biol. 165:175-180(2004).
CC -!- FUNCTION: Phosphorylates a large number of substrates in the cytoplasm
CC and the nucleus (By similarity). Phosphorylates CDC25B, ABL1, NFKB1,
CC CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (By similarity).
CC Regulates the abundance of compartmentalized pools of its regulatory
CC subunits through phosphorylation of PJA2 which binds and ubiquitinates
CC these subunits, leading to their subsequent proteolysis. RORA is
CC activated by phosphorylation. Required for glucose-mediated adipogenic
CC differentiation increase and osteogenic differentiation inhibition from
CC osteoblasts (By similarity). Involved in chondrogenesis by mediating
CC phosphorylation of SOX9 (By similarity). Involved in the regulation of
CC platelets in response to thrombin and collagen; maintains circulating
CC platelets in a resting state by phosphorylating proteins in numerous
CC platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and
CC NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt
CC these complexes and free active PRKACA stimulates platelets and leads
CC to platelet aggregation by phosphorylating VASP. RYR2 channel activity
CC is potentiated by phosphorylation in presence of luminal Ca(2+),
CC leading to reduced amplitude and increased frequency of store overload-
CC induced Ca(2+) release (SOICR) characterized by an increased rate of
CC Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves,
CC despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6
CC activation by phosphorylation stimulates proteasome. Negatively
CC regulates tight junctions (TJs) in ovarian cancer cells via CLDN3
CC phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA
CC binding. Required for phosphorylation of GLI transcription factors
CC which inhibits them and prevents transcriptional activation of Hedgehog
CC signaling pathway target genes (By similarity). GLI transcription
CC factor phosphorylation is inhibited by interaction of PRKACA with SMO
CC which sequesters PRKACA at the cell membrane (By similarity). Involved
CC in embryonic development by down-regulating the Hedgehog (Hh) signaling
CC pathway that determines embryo pattern formation and morphogenesis most
CC probably through the regulation of OFD1 in ciliogenesis (By
CC similarity). Prevents meiosis resumption in prophase-arrested oocytes
CC via CDC25B inactivation by phosphorylation (By similarity). May also
CC regulate rapid eye movement (REM) sleep in the pedunculopontine
CC tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA.
CC Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear
CC localization and transcriptional activity upon heat shock (By
CC similarity). Acts as a negative regulator of mTORC1 by mediating
CC phosphorylation of RPTOR (By similarity).
CC {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P17612,
CC ECO:0000250|UniProtKB:P27791}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; 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 -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.11;
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 The cAMP-dependent protein kinase catalytic subunit binds PJA2.
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
CC assembly. Found in a complex at least composed of MROH2B, PRKACA and
CC TCP11 (By similarity). Interacts with MROH2B (By similarity). Interacts
CC with HSF1 (By similarity). Interacts with TCP11 (By similarity).
CC Interacts with TBC1D31; in the regulation of OFD1 (By similarity).
CC Interacts in free form with SMO (via C-terminus); the interaction leads
CC to sequestration of PRKACA at the membrane, preventing PRKACA-mediated
CC phosphorylation of GLI transcription factors (By similarity).
CC {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P17612,
CC ECO:0000269|PubMed:15096524}.
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-197 is required for full activity (By similarity). Phosphorylated
CC at Tyr-330 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-10 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}.
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DR EMBL; AF525132; AAM88381.1; -; mRNA.
DR RefSeq; NP_001003032.1; NM_001003032.1.
DR AlphaFoldDB; Q8MJ44; -.
DR SMR; Q8MJ44; -.
DR IntAct; Q8MJ44; 1.
DR STRING; 9615.ENSCAFP00000053880; -.
DR iPTMnet; Q8MJ44; -.
DR PaxDb; 9612-ENSCAFP00000024262; -.
DR GeneID; 403556; -.
DR KEGG; cfa:403556; -.
DR CTD; 5566; -.
DR eggNOG; KOG0616; Eukaryota.
DR InParanoid; Q8MJ44; -.
DR OrthoDB; 10768at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR Proteomes; UP000694429; Unplaced.
DR Proteomes; UP000694542; Unplaced.
DR Proteomes; UP000805418; Unplaced.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010737; P:protein kinase A signaling; IBA:GO_Central.
DR CDD; cd14209; STKc_PKA; 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.
PE 1: Evidence at protein level;
KW ATP-binding; cAMP; Cell membrane; Cytoplasm; Kinase; Lipoprotein; Membrane;
KW Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00517"
FT CHAIN 2..350
FT /note="cAMP-dependent protein kinase catalytic subunit
FT alpha"
FT /id="PRO_0000086050"
FT DOMAIN 43..297
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 298..350
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 49..57
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 121..127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 168..171
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 10
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P05132"
FT MOD_RES 48
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P17612"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05132"
FT MOD_RES 195
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P17612"
FT MOD_RES 197
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P00517"
FT MOD_RES 330
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P05132"
FT MOD_RES 338
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00517"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P17612"
SQ SEQUENCE 350 AA; 40546 MW; DC827D8A06358E8F CRC64;
MGNAAAKKGS EQESVKEFLA KAKEDFLKKW ENPAQNTAHL DQFERIKTLG TGSFGRVMLV
KHKETGNHFA MKILDKQKVV KLKQIEHTLN EKRILQAVNF PFLVKLEFSF KDNSNLYMVM
EYVPGGEMFS HLRRIGRFSE PHARFYAAQI VLTFEYLHSL DLIYRDLKPE NLLIDQQGYI
QVTDFGFAKR VKGRTWTLCG TPEYLAPEII LSKGYNKAVD WWALGVLIYE MAAGYPPFFA
DQPIQIYEKI VSGKVRFPSH FSSDLKDLLR NLLQVDLTKR FGNLKNGVND IKNHKWFATT
DWIAIYQRKV EAPFIPKFKG PGDTSNFDDY EEEEIRVSIN EKCGKEFCEF
//
