ID KPCA_RAT Reviewed; 672 AA.
AC P05696;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 221.
DE RecName: Full=Protein kinase C alpha type;
DE Short=PKC-A;
DE Short=PKC-alpha;
DE EC=2.7.11.13;
GN Name=Prkca; Synonyms=Pkca;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3387228; DOI=10.1093/nar/16.11.5199;
RA Ono Y., Fujii T., Igarashi K., Kikkawa U., Ogita K., Nishizuka Y.;
RT "Nucleotide sequences of cDNAs for alpha and gamma subspecies of rat brain
RT protein kinase C.";
RL Nucleic Acids Res. 16:5199-5200(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3666147; DOI=10.1016/0014-5793(87)80291-0;
RA Kikkawa U., Ogita K., Ono Y., Asaoka Y., Shearman M.S., Fujii T., Ase K.,
RA Sekiguchi K., Igarashi K., Nishizuka Y.;
RT "The common structure and activities of four subspecies of rat brain
RT protein kinase C family.";
RL FEBS Lett. 223:212-216(1987).
RN [3]
RP INTERACTION WITH CAVIN2.
RX PubMed=9566962; DOI=10.1083/jcb.141.3.601;
RA Mineo C., Ying Y.-S., Chapline C., Jaken S., Anderson R.G.W.;
RT "Targeting of protein kinase Calpha to caveolae.";
RL J. Cell Biol. 141:601-610(1998).
RN [4]
RP FUNCTION IN CELL CYCLE ARREST.
RX PubMed=11076962; DOI=10.1083/jcb.151.4.763;
RA Frey M.R., Clark J.A., Leontieva O., Uronis J.M., Black A.R., Black J.D.;
RT "Protein kinase C signaling mediates a program of cell cycle withdrawal in
RT the intestinal epithelium.";
RL J. Cell Biol. 151:763-778(2000).
RN [5]
RP FUNCTION IN CARDIAC HYPERTROPHY.
RX PubMed=11864993; DOI=10.1083/jcb.200108062;
RA Braz J.C., Bueno O.F., De Windt L.J., Molkentin J.D.;
RT "PKC alpha regulates the hypertrophic growth of cardiomyocytes through
RT extracellular signal-regulated kinase1/2 (ERK1/2).";
RL J. Cell Biol. 156:905-919(2002).
RN [6]
RP FUNCTION IN HEART FAILURE, AND SUBCELLULAR LOCATION.
RX PubMed=15271671; DOI=10.1152/ajpheart.00171.2004;
RA Vijayan K., Szotek E.L., Martin J.L., Samarel A.M.;
RT "Protein kinase C-alpha-induced hypertrophy of neonatal rat ventricular
RT myocytes.";
RL Am. J. Physiol. 287:H2777-H2789(2004).
RN [7]
RP REVIEW.
RX PubMed=3045562; DOI=10.1038/334661a0;
RA Nishizuka Y.;
RT "The molecular heterogeneity of protein kinase C and its implications for
RT cellular regulation.";
RL Nature 334:661-665(1988).
RN [8]
RP FUNCTION.
RX PubMed=19176525; DOI=10.1074/jbc.m808719200;
RA Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K.;
RT "Phosphorylation of activation transcription factor-2 at serine 121 by
RT protein kinase c controls c-Jun-mediated activation of transcription.";
RL J. Biol. Chem. 284:8567-8581(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226; SER-319 AND THR-638, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 155-293 IN COMPLEX WITH
RP PHOSPHATIDYLSERINE AND CALCIUM.
RX PubMed=10562545; DOI=10.1093/emboj/18.22.6329;
RA Verdaguer N., Corbalan-Garcia S., Ochoa W.F., Fita I.,
RA Gomez-Fernandez J.C.;
RT "Ca(2+) bridges the C2 membrane-binding domain of protein kinase Calpha
RT directly to phosphatidylserine.";
RL EMBO J. 18:6329-6338(1999).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 156-292 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE AND CALCIUM, MUTAGENESIS OF TYR-195;
RP LYS-209; LYS-211 AND TRP-245, AND SUBCELLULAR LOCATION.
RX PubMed=19346474; DOI=10.1073/pnas.0813099106;
RA Guerrero-Valero M., Ferrer-Orta C., Querol-Audi J., Marin-Vicente C.,
RA Fita I., Gomez-Fernandez J.C., Verdaguer N., Corbalan-Garcia S.;
RT "Structural and mechanistic insights into the association of PKCalpha-C2
RT domain to PtdIns(4,5)P2.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6603-6607(2009).
CC -!- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that is involved in positive
CC and negative regulation of cell proliferation, apoptosis,
CC differentiation, migration and adhesion, cardiac hypertrophy,
CC angiogenesis, platelet function and inflammation, by directly
CC phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or
CC activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP.
CC Depending on the cell type, is involved in cell proliferation and cell
CC growth arrest by positive and negative regulation of the cell cycle.
CC Can promote cell growth by phosphorylating and activating RAF1, which
CC mediates the activation of the MAPK/ERK signaling cascade, and/or by
CC up-regulating CDKN1A, which facilitates active cyclin-dependent kinase
CC (CDK) complex formation. In cells stimulated by the phorbol ester PMA,
CC can trigger a cell cycle arrest program which is associated with the
CC accumulation of the hyper-phosphorylated growth-suppressive form of RB1
CC and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the
CC cell type, exhibits anti-apoptotic function and protects cells from
CC apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or
CC mediates anti-apoptotic action by phosphorylating BCL2. During
CC macrophage differentiation induced by macrophage colony-stimulating
CC factor (CSF1), is translocated to the nucleus and is associated with
CC macrophage development. After wounding, translocates from focal
CC contacts to lamellipodia and participates in the modulation of
CC desmosomal adhesion. Plays a role in cell motility by phosphorylating
CC CSPG4, which induces association of CSPG4 with extensive lamellipodia
CC at the cell periphery and polarization of the cell accompanied by
CC increases in cell motility. During chemokine-induced CD4(+) T cell
CC migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting
CC in its dissociation from LRCH1 and the activation of GTPase CDC42 (By
CC similarity). Negatively regulates myocardial contractility and
CC positively regulates angiogenesis, platelet aggregation and thrombus
CC formation in arteries. Mediates hypertrophic growth of neonatal
CC cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling
CC pathway, and upon PMA treatment, is required to induce cardiomyocyte
CC hypertrophy up to heart failure and death, by increasing protein
CC synthesis, protein-DNA ratio and cell surface area. Regulates
CC cardiomyocyte function by phosphorylating cardiac troponin T
CC (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase
CC activity, myofilament calcium sensitivity and myocardial contractility.
CC In angiogenesis, is required for full endothelial cell migration,
CC adhesion to vitronectin (VTN), and vascular endothelial growth factor A
CC (VEGFA)-dependent regulation of kinase activation and vascular tube
CC formation. Involved in the stabilization of VEGFA mRNA at post-
CC transcriptional level and mediates VEGFA-induced cell proliferation. In
CC the regulation of calcium-induced platelet aggregation, mediates
CC signals from the CD36/GP4 receptor for granule release, and activates
CC the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for
CC adhesion. During response to lipopolysaccharides (LPS), may regulate
CC selective LPS-induced macrophage functions involved in host defense and
CC inflammation. But in some inflammatory responses, may negatively
CC regulate NF-kappa-B-induced genes, through IL1A-dependent induction of
CC NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-
CC tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which
CC modulates EIF4G1 binding to MKNK1 and may be involved in the regulation
CC of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of
CC KIT activity. Phosphorylates ATF2 which promotes cooperation between
CC ATF2 and JUN, activating transcription (By similarity). Phosphorylates
CC SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal
CC degradation (By similarity). Phosphorylates KLHL3 in response to
CC angiotensin II signaling, decreasing the interaction between KLHL3 and
CC WNK4 (By similarity). {ECO:0000250|UniProtKB:P17252,
CC ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:11076962,
CC ECO:0000269|PubMed:11864993, ECO:0000269|PubMed:15271671,
CC ECO:0000269|PubMed:19176525}.
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=2.7.11.13;
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=2.7.11.13;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041,
CC ECO:0000269|PubMed:10562545, ECO:0000269|PubMed:19346474};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000269|PubMed:10562545, ECO:0000269|PubMed:19346474};
CC -!- ACTIVITY REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and
CC PRKCG) are activated by calcium and diacylglycerol (DAG) in the
CC presence of phosphatidylserine. Three specific sites; Thr-497
CC (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-
CC 657 (hydrophobic region), need to be phosphorylated for its full
CC activation.
CC -!- SUBUNIT: Interacts with ADAP1/CENTA1, CSPG4 and PRKCABP (By
CC similarity). Binds to CAVIN2 in the presence of phosphatidylserine
CC (PubMed:9566962). Interacts with PICK1 (via PDZ domain) (By
CC similarity). Interacts with TRIM41 (By similarity). Recruited in a
CC circadian manner into a nuclear complex which also includes BMAL1 and
CC RACK1 (By similarity). Interacts with PARD3 (By similarity). Interacts
CC with SOCS2 (By similarity). {ECO:0000250|UniProtKB:P17252,
CC ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:9566962}.
CC -!- INTERACTION:
CC P05696; P34901: Sdc4; NbExp=3; IntAct=EBI-935801, EBI-1173182;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15271671}. Cell
CC membrane {ECO:0000269|PubMed:15271671, ECO:0000269|PubMed:19346474};
CC Peripheral membrane protein {ECO:0000305|PubMed:15271671}.
CC Mitochondrion membrane {ECO:0000250|UniProtKB:P17252}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P17252}. Nucleus
CC {ECO:0000269|PubMed:15271671}. Note=Translocated to the nucleus upon
CC treatment with PMA or IGF1. {ECO:0000269|PubMed:15271671}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; X07286; CAA30266.1; -; mRNA.
DR PIR; S02248; KIRTC.
DR PDB; 1DSY; X-ray; 2.60 A; A=155-293.
DR PDB; 2NCE; NMR; -; A=155-293.
DR PDB; 3GPE; X-ray; 2.00 A; A=156-292.
DR PDB; 3RDJ; X-ray; 1.90 A; A=156-292.
DR PDB; 3TWY; X-ray; 1.50 A; A=156-292.
DR PDB; 4L1L; X-ray; 1.60 A; A=155-293.
DR PDB; 5W4S; NMR; -; A=155-293.
DR PDBsum; 1DSY; -.
DR PDBsum; 2NCE; -.
DR PDBsum; 3GPE; -.
DR PDBsum; 3RDJ; -.
DR PDBsum; 3TWY; -.
DR PDBsum; 4L1L; -.
DR PDBsum; 5W4S; -.
DR AlphaFoldDB; P05696; -.
DR BMRB; P05696; -.
DR SMR; P05696; -.
DR CORUM; P05696; -.
DR IntAct; P05696; 9.
DR MINT; P05696; -.
DR STRING; 10116.ENSRNOP00000004699; -.
DR BindingDB; P05696; -.
DR ChEMBL; CHEMBL2855; -.
DR DrugCentral; P05696; -.
DR GlyGen; P05696; 6 sites, 1 O-linked glycan (6 sites).
DR iPTMnet; P05696; -.
DR PhosphoSitePlus; P05696; -.
DR SwissPalm; P05696; -.
DR jPOST; P05696; -.
DR PaxDb; 10116-ENSRNOP00000004699; -.
DR Ensembl; ENSRNOT00000004699.9; ENSRNOP00000004699.8; ENSRNOG00000003491.9.
DR Ensembl; ENSRNOT00055050566; ENSRNOP00055041646; ENSRNOG00055029138.
DR Ensembl; ENSRNOT00060023763; ENSRNOP00060018914; ENSRNOG00060013871.
DR Ensembl; ENSRNOT00065032081; ENSRNOP00065025598; ENSRNOG00065019003.
DR AGR; RGD:3395; -.
DR RGD; 3395; Prkca.
DR eggNOG; KOG0696; Eukaryota.
DR GeneTree; ENSGT00940000156104; -.
DR InParanoid; P05696; -.
DR PhylomeDB; P05696; -.
DR BRENDA; 2.7.11.13; 5301.
DR Reactome; R-RNO-111933; Calmodulin induced events.
DR Reactome; R-RNO-114516; Disinhibition of SNARE formation.
DR Reactome; R-RNO-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-1433559; Regulation of KIT signaling.
DR Reactome; R-RNO-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-RNO-3000170; Syndecan interactions.
DR Reactome; R-RNO-399997; Acetylcholine regulates insulin secretion.
DR Reactome; R-RNO-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-RNO-4419969; Depolymerization of the Nuclear Lamina.
DR Reactome; R-RNO-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR Reactome; R-RNO-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-RNO-76005; Response to elevated platelet cytosolic Ca2+.
DR Reactome; R-RNO-8853659; RET signaling.
DR EvolutionaryTrace; P05696; -.
DR PRO; PR:P05696; -.
DR Proteomes; UP000002494; Chromosome 10.
DR GO; GO:0035866; C:alphav-beta3 integrin-PKCalpha complex; ISO:RGD.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0044305; C:calyx of Held; ISO:RGD.
DR GO; GO:0036064; C:ciliary basal body; ISO:RGD.
DR GO; GO:0120199; C:cone photoreceptor outer segment; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0014704; C:intercalated disc; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:1990917; C:ooplasm; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0099523; C:presynaptic cytosol; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium,diacylglycerol-dependent serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0035403; F:histone H3T6 kinase activity; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0008289; F:lipid binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071322; P:cellular response to carbohydrate stimulus; ISO:RGD.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:RGD.
DR GO; GO:0002062; P:chondrocyte differentiation; ISO:RGD.
DR GO; GO:0002159; P:desmosome assembly; ISO:RGD.
DR GO; GO:0045184; P:establishment of protein localization; TAS:UniProtKB.
DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:RGD.
DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; IMP:RGD.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0046325; P:negative regulation of glucose import; ISO:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0017148; P:negative regulation of translation; IMP:RGD.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0110063; P:positive regulation of angiotensin-activated signaling pathway; ISO:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISO:RGD.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:2000707; P:positive regulation of dense core granule biogenesis; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:RGD.
DR GO; GO:0043687; P:post-translational protein modification; ISO:RGD.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:RGD.
DR GO; GO:0006937; P:regulation of muscle contraction; ISO:RGD.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0048259; P:regulation of receptor-mediated endocytosis; IMP:RGD.
DR GO; GO:0047484; P:regulation of response to osmotic stress; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IMP:RGD.
DR GO; GO:0045471; P:response to ethanol; IMP:RGD.
DR GO; GO:0070555; P:response to interleukin-1; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0000302; P:response to reactive oxygen species; IMP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0048863; P:stem cell differentiation; ISO:RGD.
DR CDD; cd20833; C1_cPKC_rpt1; 1.
DR CDD; cd20836; C1_cPKC_rpt2; 1.
DR CDD; cd04026; C2_PKC_alpha_gamma; 1.
DR CDD; cd05615; STKc_cPKC_alpha; 1.
DR Gene3D; 3.30.60.20; -; 2.
DR Gene3D; 2.60.40.150; C2 domain; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR034663; cPKC_alpha.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014375; Protein_kinase_C_a/b/g.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351:SF242; PROTEIN KINASE C; 1.
DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000550; PKC_alpha; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR SUPFAM; SSF57889; Cysteine-rich domain; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Angiogenesis; Apoptosis; ATP-binding; Calcium;
KW Cell adhesion; Cell membrane; Cytoplasm; Kinase; Membrane; Metal-binding;
KW Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT CHAIN 2..672
FT /note="Protein kinase C alpha type"
FT /id="PRO_0000055682"
FT DOMAIN 158..275
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 339..597
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 598..668
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 36..86
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 101..151
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 463
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10562545"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 195
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000269|PubMed:19346474"
FT BINDING 245
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000269|PubMed:19346474"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10562545,
FT ECO:0000269|PubMed:19346474"
FT BINDING 345..353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 494
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 497
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 501
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05771"
FT MOD_RES 628
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 631
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 638
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17252"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05771"
FT MOD_RES 658
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:P20444"
FT MUTAGEN 195
FT /note="Y->S: Reduced phosphatidylinositol 4,5-bisphosphate
FT recognition and impaired membrane docking. Loss of
FT phosphatidylinositol 4,5-bisphosphate-binding and strong
FT decrease of membrane docking; when associated with A-209;
FT A-211 and A-245."
FT /evidence="ECO:0000269|PubMed:19346474"
FT MUTAGEN 209
FT /note="K->A: Loss of phosphatidylinositol 4,5-bisphosphate-
FT binding and strong decrease of membrane docking; when
FT associated with S-195; A-211 and A-245."
FT /evidence="ECO:0000269|PubMed:19346474"
FT MUTAGEN 211
FT /note="K->A: Loss of phosphatidylinositol 4,5-bisphosphate-
FT binding and strong decrease of membrane docking; when
FT associated with S-195; A-209 and A-245."
FT /evidence="ECO:0000269|PubMed:19346474"
FT MUTAGEN 245
FT /note="W->A: Reduced phosphatidylinositol 4,5-bisphosphate
FT recognition and impaired membrane docking. Loss of
FT phosphatidylinositol 4,5-bisphosphate-binding and strong
FT decrease of membrane docking; when associated with S-195;
FT A-209 and A-211."
FT /evidence="ECO:0000269|PubMed:19346474"
FT STRAND 161..169
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 172..182
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 194..201
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:3TWY"
FT HELIX 233..237
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 254..262
FT /evidence="ECO:0007829|PDB:3TWY"
FT HELIX 263..268
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 271..276
FT /evidence="ECO:0007829|PDB:3TWY"
FT HELIX 280..283
FT /evidence="ECO:0007829|PDB:3TWY"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:1DSY"
SQ SEQUENCE 672 AA; 76792 MW; 94889E7339C17719 CRC64;
MADVYPANDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC SHCTDFIWGF
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS KHKFKIHTYG SPTFCDHCGS
LLYGLIHQGM KCDTCDMNVH KQCVINVPSL CGMDHTEKRG RIYLKAEVTD EKLHVTVRDA
KNLIPMDPNG LSDPYVKLKL IPDPKNESKQ KTKTIRSTLN PQWNESFTFK LKPSDKDRRL
SVEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKLLNQ EEGEYYNVPI PEGDEEGNVE
LRQKFEKAKL GPAGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF GKVMLADRKG
TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALLDKPPFL TQLHSCFQTV DRLYFVMEYV
NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG LFFLHKRGII YRDLKLDNVM LDSEGHIKIA
DFGMCKEHMM DGVTTRTFCG TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG
EDEDELFQSI MEHNVSYPKS LSKEAVSICK GLMTKHPAKR LGCGPEGERD VREHAFFRRI
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVLTPP DQLVIANIDQ SDFEGFSYVN
PQFVHPILQS AV
//
