KAPCA_PIG
ID KAPCA_PIG Reviewed; 351 AA.
AC P36887;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 163.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 195-351.
RX PubMed=2441988; DOI=10.1111/j.1432-1033.1987.tb13326.x;
RA Adavani S.R., Schwarz M., Showers M.O., Maurer R.A., Hemmings B.A.;
RT "Multiple mRNA species code for the catalytic subunit of the cAMP-dependent
RT protein kinase from LLC-PK1 cells. Evidence for two forms of the catalytic
RT subunit.";
RL Eur. J. Biochem. 167:221-226(1987).
RN [2]
RP PROTEIN SEQUENCE OF 2-8, MYRISTOYLATION AT GLY-2, AND DEAMIDATION AT ASN-3.
RX PubMed=9521123; DOI=10.1002/pro.5560070227;
RA Jedrzejewski P.T., Girod A., Tholey A., Koenig N., Thullner S., Kinzel V.,
RA Bossemeyer D.;
RT "A conserved deamidation site at Asn 2 in the catalytic subunit of
RT mammalian cAMP-dependent protein kinase detected by capillary LC-MS and
RT tandem mass spectrometry.";
RL Protein Sci. 7:457-469(1998).
RN [3]
RP DEAMIDATION AT ASN-3, AND SUBCELLULAR LOCATION.
RX PubMed=10684253; DOI=10.1083/jcb.148.4.715;
RA Pepperkok R., Hotz-Wagenblatt A., Koenig N., Girod A., Bossemeyer D.,
RA Kinzel V.;
RT "Intracellular distribution of mammalian protein kinase A catalytic subunit
RT altered by conserved Asn2 deamidation.";
RL J. Cell Biol. 148:715-726(2000).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH PKIA.
RX PubMed=8443157; DOI=10.1021/bi00060a005;
RA Zheng J., Knighton D.R., ten Eyck L.F., Karlsson R., Xuong N.-H.,
RA Taylor S.S., Sowadski J.M.;
RT "Crystal structure of the catalytic subunit of cAMP-dependent protein
RT kinase complexed with MgATP and peptide inhibitor.";
RL Biochemistry 32:2154-2161(1993).
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. Involved in embryonic development by down-regulating the
CC Hedgehog (Hh) signaling pathway that determines embryo pattern
CC formation and morphogenesis (By similarity). Prevents meiosis
CC resumption in prophase-arrested oocytes via CDC25B inactivation by
CC phosphorylation (By similarity). May also regulate rapid eye movement
CC (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity).
CC Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this
CC phosphorylation promotes HSF1 nuclear localization and transcriptional
CC activity upon heat shock (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 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 TCP11 (By similarity). Interacts with HSF1 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P05132,
CC ECO:0000250|UniProtKB:P17612}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Nucleus {ECO:0000250}. Mitochondrion {ECO:0000250}.
CC Membrane {ECO:0000250|UniProtKB:P17612}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P17612}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:P05132}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250|UniProtKB:P05132}. Note=Translocates into the
CC nucleus (monomeric catalytic subunit). The inactive holoenzyme is found
CC in the cytoplasm. Distributed throughout the cytoplasm in meiotically
CC incompetent oocytes. Associated to mitochondrion as meiotic competence
CC is acquired. Aggregates around the germinal vesicles (GV) at the
CC immature GV stage oocytes (By similarity). Expressed in the midpiece
CC region of the sperm flagellum (By similarity). Colocalizes with MROH2B
CC and TCP11 on the acrosome and tail regions in round spermatids and
CC spermatozoa regardless of the capacitation status of the sperm (By
CC similarity). Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon
CC heat shock (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P05132,
CC ECO:0000250|UniProtKB:P17612}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in mammalian tissues.
CC -!- PTM: Asn-3 is deaminated to Asp in more than 25% of the proteins,
CC giving rise to 2 major isoelectric variants, called CB and CA
CC respectively (0.4 pH unit change). Deamidation proceeds via the so-
CC called beta-aspartyl shift mechanism and yields either 'D-Asp-2'
CC (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation
CC occurs after the addition of myristate. The Asn-3 form reaches a
CC significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.
CC {ECO:0000269|PubMed:10684253, ECO:0000269|PubMed:9521123}.
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). {ECO:0000250}.
CC -!- PTM: Phosphorylated at Tyr-331 by activated receptor tyrosine kinases
CC EGFR and PDGFR; this increases catalytic efficiency. {ECO:0000250}.
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; X07617; CAA30470.1; -; mRNA.
DR PIR; S00086; S00086.
DR PDB; 1CDK; X-ray; 2.00 A; A/B=2-351.
DR PDB; 1CMK; X-ray; 2.90 A; E=2-351.
DR PDB; 1CTP; X-ray; 2.90 A; E=2-351.
DR PDBsum; 1CDK; -.
DR PDBsum; 1CMK; -.
DR PDBsum; 1CTP; -.
DR AlphaFoldDB; P36887; -.
DR SMR; P36887; -.
DR IntAct; P36887; 1.
DR STRING; 9823.ENSSSCP00000014641; -.
DR iPTMnet; P36887; -.
DR PaxDb; P36887; -.
DR PeptideAtlas; P36887; -.
DR PRIDE; P36887; -.
DR eggNOG; KOG0616; Eukaryota.
DR InParanoid; P36887; -.
DR EvolutionaryTrace; P36887; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IMP:AgBase.
DR GO; GO:0042585; C:germinal vesicle; IMP:AgBase.
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; IMP:AgBase.
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:1904145; P:negative regulation of meiotic cell cycle process involved in oocyte maturation; IMP:AgBase.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR CDD; cd14209; STKc_PKA; 1.
DR IDEAL; IID50158; -.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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 3D-structure; ATP-binding; cAMP; Cell membrane; Cell projection; Cilium;
KW Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing; Flagellum;
KW Kinase; Lipoprotein; Membrane; Mitochondrion; Myristate;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9521123"
FT CHAIN 2..351
FT /note="cAMP-dependent protein kinase catalytic subunit
FT alpha"
FT /id="PRO_0000086054"
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 BINDING 73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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; partial"
FT /evidence="ECO:0000269|PubMed:10684253,
FT ECO:0000269|PubMed:9521123"
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:0000269|PubMed:9521123"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:1CMK"
FT HELIX 11..32
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 44..52
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:1CDK"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 69..76
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 77..82
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 141..160
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:1CDK"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 208..211
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 220..234
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:1CDK"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:1CDK"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:1CTP"
FT TURN 286..289
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 290..293
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:1CDK"
FT HELIX 303..307
FT /evidence="ECO:0007829|PDB:1CDK"
FT TURN 322..328
FT /evidence="ECO:0007829|PDB:1CMK"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:1CDK"
SQ SEQUENCE 351 AA; 40617 MW; B65EC7C42DD56DE5 CRC64;
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WENPAQNTAH LDQFERIKTL GTGSFGRVML
VKHKETGNHF AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEYS FKDNSNLYMV
MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY
IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF
ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFSE F
