KPCA_MOUSE
ID KPCA_MOUSE Reviewed; 672 AA.
AC P20444;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 216.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2469625; DOI=10.1016/0378-1119(88)90179-5;
RA Rose-John S., Dietrich A., Marks F.;
RT "Molecular cloning of mouse protein kinase C (PKC) cDNA from Swiss 3T3
RT fibroblasts.";
RL Gene 74:465-471(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS VAL-106; GLY-111; GLN-240 AND
RP LEU-339.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=2601739; DOI=10.1038/342807a0;
RA Megidish T., Mazurek N.;
RT "A mutant protein kinase C that can transform fibroblasts.";
RL Nature 342:807-811(1989).
RN [3]
RP FUNCTION IN PHOSPHORYLATION OF RAF1.
RX PubMed=8321321; DOI=10.1038/364249a0;
RA Kolch W., Heidecker G., Kochs G., Hummel R., Vahidi H., Mischak H.,
RA Finkenzeller G., Marme D., Rapp U.R.;
RT "Protein kinase C alpha activates RAF-1 by direct phosphorylation.";
RL Nature 364:249-252(1993).
RN [4]
RP INTERACTION WITH PRKCABP.
RX PubMed=7844141; DOI=10.1083/jcb.128.3.263;
RA Staudinger J., Zhou J., Burgess R., Elledge S.J., Olson E.N.;
RT "PICK1: a perinuclear binding protein and substrate for protein kinase C
RT isolated by the yeast two-hybrid system.";
RL J. Cell Biol. 128:263-271(1995).
RN [5]
RP FUNCTION IN CELL PROLIFERATION.
RX PubMed=9508782; DOI=10.1083/jcb.140.6.1511;
RA Pierce A., Heyworth C.M., Nicholls S.E., Spooncer E., Dexter T.M.,
RA Lord J.M., Owen-Lynch P.J., Wark G., Whetton A.D.;
RT "An activated protein kinase C alpha gives a differentiation signal for
RT hematopoietic progenitor cells and mimicks macrophage colony-stimulating
RT factor-stimulated signaling events.";
RL J. Cell Biol. 140:1511-1518(1998).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=10092232; DOI=10.1126/science.283.5410.2085;
RA Ng T., Squire A., Hansra G., Bornancin F., Prevostel C., Hanby A.,
RA Harris W., Barnes D., Schmidt S., Mellor H., Bastiaens P.I., Parker P.J.;
RT "Imaging protein kinase Calpha activation in cells.";
RL Science 283:2085-2089(1999).
RN [7]
RP PHOSPHORYLATION AT TYR-658.
RX PubMed=12881490; DOI=10.1073/pnas.1633695100;
RA Kawakami Y., Kitaura J., Yao L., McHenry R.W., Kawakami Y., Newton A.C.,
RA Kang S., Kato R.M., Leitges M., Rawlings D.J., Kawakami T.;
RT "A Ras activation pathway dependent on Syk phosphorylation of protein
RT kinase C.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9470-9475(2003).
RN [8]
RP FUNCTION IN PLATELET GRANULE SECRETION.
RX PubMed=19147982; DOI=10.1172/jci34665;
RA Konopatskaya O., Gilio K., Harper M.T., Zhao Y., Cosemans J.M., Karim Z.A.,
RA Whiteheart S.W., Molkentin J.D., Verkade P., Watson S.P., Heemskerk J.W.,
RA Poole A.W.;
RT "PKCalpha regulates platelet granule secretion and thrombus formation in
RT mice.";
RL J. Clin. Invest. 119:399-407(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Liver, Lung, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP INTERACTION WITH BMAL1 AND RACK1, AND SUBCELLULAR LOCATION.
RX PubMed=20093473; DOI=10.1126/science.1180067;
RA Robles M.S., Boyault C., Knutti D., Padmanabhan K., Weitz C.J.;
RT "Identification of RACK1 and protein kinase Calpha as integral components
RT of the mammalian circadian clock.";
RL Science 327:463-466(2010).
RN [11]
RP FUNCTION, AND INTERACTION WITH SOSC2.
RX PubMed=31578312; DOI=10.1172/jci.insight.129110;
RA Lear T.B., McKelvey A.C., Evankovich J.W., Rajbhandari S., Coon T.A.,
RA Dunn S.R., Londino J.D., McVerry B.J., Zhang Y., Valenzi E., Burton C.L.,
RA Gordon R., Gingras S., Lockwood K.C., Jurczak M.J., Lafyatis R.,
RA Shlomchik M.J., Liu Y., Chen B.B.;
RT "KIAA0317 regulates pulmonary inflammation through SOCS2 degradation.";
RL JCI Insight 4:0-0(2019).
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. Phosphorylates SOCS2 at 'Ser-
CC 52' facilitating its ubiquitination and proteosomal degradation
CC (PubMed:31578312). {ECO:0000250|UniProtKB:P17252,
CC ECO:0000269|PubMed:19147982, ECO:0000269|PubMed:31578312,
CC ECO:0000269|PubMed:8321321, ECO:0000269|PubMed:9508782}.
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 Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000250|UniProtKB:P05696};
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 and CSPG4 (By similarity).
CC Interacts with PRKCABP (PubMed:7844141). Binds to CAVIN2 in the
CC presence of phosphatidylserine. Interacts with PICK1 (via PDZ domain).
CC Interacts with TRIM41 (By similarity). Recruited in a circadian manner
CC into a nuclear complex which also includes BMAL1 and RACK1
CC (PubMed:20093473). Interacts with PARD3 (By similarity). Interacts with
CC SOCS2 (PubMed:31578312). {ECO:0000250|UniProtKB:P05696,
CC ECO:0000250|UniProtKB:P17252, ECO:0000269|PubMed:20093473,
CC ECO:0000269|PubMed:31578312, ECO:0000269|PubMed:7844141}.
CC -!- INTERACTION:
CC P20444; O08785: Clock; NbExp=3; IntAct=EBI-6976815, EBI-79859;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10092232,
CC ECO:0000269|PubMed:20093473}. Cell membrane
CC {ECO:0000269|PubMed:10092232}; Peripheral membrane protein
CC {ECO:0000305|PubMed:10092232}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:P17252}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17252}. Nucleus {ECO:0000269|PubMed:20093473}.
CC Note=Translocated to the cell periphery upon tetradecanoyl phorbol
CC acetate (TPA) treatment.
CC -!- DISEASE: Note=Expression of the mutant form UV25 causes malignant
CC transformation of cells.
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; M25811; AAA39934.1; -; mRNA.
DR EMBL; X52685; CAA36908.1; -; mRNA.
DR EMBL; X52684; CAA36907.1; -; mRNA.
DR PIR; S07104; KIMSCA.
DR RefSeq; NP_035231.2; NM_011101.3.
DR AlphaFoldDB; P20444; -.
DR BMRB; P20444; -.
DR SMR; P20444; -.
DR BioGRID; 202194; 28.
DR CORUM; P20444; -.
DR DIP; DIP-532N; -.
DR IntAct; P20444; 5.
DR MINT; P20444; -.
DR STRING; 10090.ENSMUSP00000062392; -.
DR BindingDB; P20444; -.
DR ChEMBL; CHEMBL2567; -.
DR iPTMnet; P20444; -.
DR PhosphoSitePlus; P20444; -.
DR SwissPalm; P20444; -.
DR EPD; P20444; -.
DR jPOST; P20444; -.
DR MaxQB; P20444; -.
DR PaxDb; P20444; -.
DR PeptideAtlas; P20444; -.
DR PRIDE; P20444; -.
DR ProteomicsDB; 263674; -.
DR DNASU; 18750; -.
DR GeneID; 18750; -.
DR KEGG; mmu:18750; -.
DR CTD; 5578; -.
DR MGI; MGI:97595; Prkca.
DR eggNOG; KOG0696; Eukaryota.
DR InParanoid; P20444; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; P20444; -.
DR BRENDA; 2.7.11.13; 3474.
DR Reactome; R-MMU-111933; Calmodulin induced events.
DR Reactome; R-MMU-114516; Disinhibition of SNARE formation.
DR Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-MMU-3000170; Syndecan interactions.
DR Reactome; R-MMU-399997; Acetylcholine regulates insulin secretion.
DR Reactome; R-MMU-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-MMU-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-MMU-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR Reactome; R-MMU-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-MMU-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-76005; Response to elevated platelet cytosolic Ca2+.
DR Reactome; R-MMU-8853659; RET signaling.
DR BioGRID-ORCS; 18750; 2 hits in 78 CRISPR screens.
DR ChiTaRS; Prkca; mouse.
DR PRO; PR:P20444; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P20444; protein.
DR GO; GO:0035866; C:alphav-beta3 integrin-PKCalpha complex; IDA:BHF-UCL.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0044305; C:calyx of Held; IDA:SynGO.
DR GO; GO:0120199; C:cone photoreceptor outer segment; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0014704; C:intercalated disc; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:1990917; C:ooplasm; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0099523; C:presynaptic cytosol; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0035403; F:histone kinase activity (H3-T6 specific); ISO:MGI.
DR GO; GO:0005178; F:integrin binding; IPI:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0004697; F:protein kinase C activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
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; IGI:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:0071322; P:cellular response to carbohydrate stimulus; IDA:MGI.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISO:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:MGI.
DR GO; GO:0002159; P:desmosome assembly; ISO:MGI.
DR GO; GO:0035408; P:histone H3-T6 phosphorylation; ISO:MGI.
DR GO; GO:0050930; P:induction of positive chemotaxis; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0007611; P:learning or memory; ISO:MGI.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:MGI.
DR GO; GO:0010360; P:negative regulation of anion channel activity; IMP:CAFA.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0046325; P:negative regulation of glucose import; IMP:MGI.
DR GO; GO:0045822; P:negative regulation of heart contraction; ISO:MGI.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0030593; P:neutrophil chemotaxis; IMP:MGI.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IDA:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0045780; P:positive regulation of bone resorption; IMP:BHF-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS: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; IMP: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; ISS:UniProtKB.
DR GO; GO:0045921; P:positive regulation of exocytosis; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:MGI.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:MGI.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IDA:SynGO.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006937; P:regulation of muscle contraction; IMP:MGI.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0090330; P:regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0048259; P:regulation of receptor-mediated endocytosis; ISO:MGI.
DR GO; GO:0047484; P:regulation of response to osmotic stress; IMP:CAFA.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IMP:MGI.
DR GO; GO:0032355; P:response to estradiol; ISO:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0070555; P:response to interleukin-1; ISO:MGI.
DR GO; GO:0000302; P:response to reactive oxygen species; ISO:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
DR CDD; cd00029; C1; 2.
DR CDD; cd05615; STKc_cPKC_alpha; 1.
DR DisProt; DP01105; -.
DR Gene3D; 2.60.40.150; -; 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 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; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
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 Acetylation; Angiogenesis; Apoptosis; ATP-binding; Calcium; Cell adhesion;
KW Cell membrane; Cytoplasm; Kinase; Membrane; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; 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_0000055680"
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:0000250|UniProtKB:P05696"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
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:0000250|UniProtKB:P05696"
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:0000250|UniProtKB:P05696"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
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:0000250|UniProtKB:P17252"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05696"
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; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17252"
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:0000269|PubMed:12881490"
FT VARIANT 106
FT /note="I -> V (in mutant form UV25)"
FT /evidence="ECO:0000269|PubMed:2601739"
FT VARIANT 111
FT /note="S -> G (in mutant form UV25)"
FT /evidence="ECO:0000269|PubMed:2601739"
FT VARIANT 240
FT /note="L -> Q (in mutant form UV25)"
FT /evidence="ECO:0000269|PubMed:2601739"
FT VARIANT 339
FT /note="F -> L (in mutant form UV25)"
FT /evidence="ECO:0000269|PubMed:2601739"
FT CONFLICT 147
FT /note="D -> V (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="N -> T (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
FT CONFLICT 277..278
FT /note="AH -> LL (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="V -> A (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="N -> D (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="N -> D (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="Q -> H (in Ref. 1; CAA36908/CAA36907)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 672 AA; 76852 MW; 394B48C952BB6D50 CRC64;
MADVYPANDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC SHCTDFIWGF
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS KHKFKIHTYG SPTFCDHCGS
LLYGLIHQGM KCDTCDMNVH KQCVINDPSL CGMDHTEKRG RIYLKAEVTD EKLHVTVRDA
KNLIPMDPNG LSDPYVKLKL IPDPKNESKQ KTKTIRSNLN PQWNESFTFK LKPSDKDRRL
SVEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKAHNQ EEGEYYNVPI PEGDEEGNME
LRQKFEKAKL GPVGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF GKVMLADRKG
TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALLDKPPFL TQLHSCFQTV DRLYFVMEYV
NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG LFFLHKRGII YRDLKLNNVM LNSEGHIKIA
DFGMCKEHMM DGVTTRTFCG TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG
EDEDELFQSI MEHNVSYPKS LSKEAVSICK GLMTKQPAKR LGCGPEGERD VREHAFFRRI
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVLTPP DQLVIANIDQ SDFEGFSYVN
PQFVHPILQS AV
