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P17252 (KPCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 171. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C alpha type

Short name=PKC-A
Short name=PKC-alpha
EC=2.7.11.13
Gene names
Name:PRKCA
Synonyms:PKCA, PRKACA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length672 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.25 Ref.30 Ref.35 Ref.39

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 3 calcium ions per subunit. The ions are bound to the C2 domain By similarity.

Enzyme regulation

Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation.

Subunit structure

Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and GNB2L1/RACK1 By similarity. Interacts with ADAP1/CENTA1, CSPG4 and PRKCABP. Binds to SDPR in the presence of phosphatidylserine. Interacts with PICK1 (via PDZ domain). Interacts with TRIM41. Ref.15 Ref.20 Ref.21 Ref.24

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein. Mitochondrion membrane; Peripheral membrane protein Probable. Nucleus Ref.9 Ref.39.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAngiogenesis
Apoptosis
Cell adhesion
   Cellular componentCell membrane
Cytoplasm
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseProto-oncogene
   DomainRepeat
Zinc-finger
   LigandATP-binding
Calcium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processRNA metabolic process

Traceable author statement. Source: Reactome

activation of adenylate cyclase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

activation of phospholipase C activity

Traceable author statement. Source: Reactome

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic signaling pathway

Traceable author statement PubMed 10825394. Source: ProtInc

blood coagulation

Traceable author statement. Source: Reactome

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cellular calcium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

cellular response to carbohydrate stimulus

Inferred from electronic annotation. Source: Ensembl

chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

desmosome assembly

Inferred from mutant phenotype PubMed 18474624. Source: BHF-UCL

energy reserve metabolic process

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

histone H3-T6 phosphorylation

Inferred from direct assay PubMed 20228790. Source: UniProtKB

inactivation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

induction of positive chemotaxis

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

mRNA metabolic process

Traceable author statement. Source: Reactome

negative regulation of adenylate cyclase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of glial cell apoptotic process

Inferred from mutant phenotype Ref.12. Source: UniProtKB

negative regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

neutrophil chemotaxis

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine autophosphorylation

Inferred from electronic annotation. Source: Ensembl

phototransduction, visible light

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from mutant phenotype Ref.14. Source: UniProtKB

positive regulation of blood vessel endothelial cell migration

Inferred from direct assay PubMed 20011604. Source: DFLAT

positive regulation of cardiac muscle hypertrophy

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell adhesion

Inferred from mutant phenotype Ref.14. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype Ref.39. Source: UniProtKB

positive regulation of dense core granule biogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell migration

Inferred from mutant phenotype Ref.14. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from mutant phenotype Ref.14. Source: UniProtKB

positive regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

positive regulation of lipopolysaccharide-mediated signaling pathway

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of macrophage differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 10770950. Source: UniProtKB

regulation of insulin secretion

Traceable author statement. Source: Reactome

regulation of muscle contraction

Inferred from electronic annotation. Source: Ensembl

regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of platelet aggregation

Inferred from direct assay Ref.16. Source: UniProtKB

regulation of rhodopsin mediated signaling pathway

Traceable author statement. Source: Reactome

regulation of the force of heart contraction

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from mutant phenotype PubMed 19281832. Source: BHF-UCL

rhodopsin mediated signaling pathway

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15632189Ref.39. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 17983652. Source: UniProtKB

dendrite

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from direct assay PubMed 18556656. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay PubMed 20833797. Source: UniProt

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

photoreceptor outer segment

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay PubMed 15632189Ref.39. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium-dependent protein kinase C activity

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction. Source: BHF-UCL

histone kinase activity (H3-T6 specific)

Inferred from direct assay PubMed 20228790. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.15PubMed 17244820. Source: UniProtKB

protein kinase C activity

Inferred from sequence or structural similarity. Source: BHF-UCL

protein kinase activity

Inferred from direct assay PubMed 10770950. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8 Ref.29
Chain2 – 672671Protein kinase C alpha type
PRO_0000055679

Regions

Domain172 – 26089C2
Domain339 – 597259Protein kinase
Domain598 – 66871AGC-kinase C-terminal
Zinc finger36 – 8651Phorbol-ester/DAG-type 1
Zinc finger101 – 15151Phorbol-ester/DAG-type 2
Nucleotide binding345 – 3539ATP By similarity

Sites

Active site4631Proton acceptor By similarity
Metal binding1861Calcium 1; via carbonyl oxygen By similarity
Metal binding1871Calcium 1 By similarity
Metal binding1871Calcium 2 By similarity
Metal binding1931Calcium 2 By similarity
Metal binding2461Calcium 1 By similarity
Metal binding2461Calcium 2 By similarity
Metal binding2471Calcium 2; via carbonyl oxygen By similarity
Metal binding2481Calcium 1 By similarity
Metal binding2481Calcium 2 By similarity
Metal binding2481Calcium 3 By similarity
Metal binding2521Calcium 3; via carbonyl oxygen By similarity
Metal binding2541Calcium 1 By similarity
Metal binding2541Calcium 3 By similarity
Binding site1951Inositol phosphate group By similarity
Binding site2451Inositol phosphate group By similarity
Binding site3681ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.29 Ref.38
Modified residue2261Phosphoserine Ref.28 Ref.31 Ref.33
Modified residue2501Phosphothreonine; by autocatalysis
Modified residue4971Phosphothreonine; by PDPK1 Probable
Modified residue6281N6-acetyllysine Ref.32
Modified residue6311Phosphothreonine; by autocatalysis Potential
Modified residue6381Phosphothreonine; by autocatalysis Ref.27 Ref.33
Modified residue6511Phosphoserine Ref.27
Modified residue6571Phosphoserine By similarity
Modified residue6581Phosphotyrosine; by SYK By similarity

Natural variations

Natural variant981P → S in a colorectal adenocarcinoma sample; somatic mutation. Ref.42
VAR_042301
Natural variant4671D → N in a glioblastoma multiforme sample; somatic mutation. Ref.42
VAR_042302
Natural variant4891M → V. Ref.42
Corresponds to variant rs34406842 [ dbSNP | Ensembl ].
VAR_042303
Natural variant5681V → I. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs6504459 [ dbSNP | Ensembl ].
VAR_050558

Experimental info

Sequence conflict501C → S in AAA60098. Ref.6

Secondary structure

.................................................................................... 672
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P17252 [UniParc].

Last modified January 11, 2011. Version 4.
Checksum: 9EB157789A062349

FASTA67276,750
        10         20         30         40         50         60 
MADVFPGNDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC SHCTDFIWGF 

        70         80         90        100        110        120 
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS KHKFKIHTYG SPTFCDHCGS 

       130        140        150        160        170        180 
LLYGLIHQGM KCDTCDMNVH KQCVINVPSL CGMDHTEKRG RIYLKAEVAD EKLHVTVRDA 

       190        200        210        220        230        240 
KNLIPMDPNG LSDPYVKLKL IPDPKNESKQ KTKTIRSTLN PQWNESFTFK LKPSDKDRRL 

       250        260        270        280        290        300 
SVEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKLLNQ EEGEYYNVPI PEGDEEGNME 

       310        320        330        340        350        360 
LRQKFEKAKL GPAGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF GKVMLADRKG 

       370        380        390        400        410        420 
TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALLDKPPFL TQLHSCFQTV DRLYFVMEYV 

       430        440        450        460        470        480 
NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG LFFLHKRGII YRDLKLDNVM LDSEGHIKIA 

       490        500        510        520        530        540 
DFGMCKEHMM DGVTTRTFCG TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG 

       550        560        570        580        590        600 
EDEDELFQSI MEHNVSYPKS LSKEAVSVCK GLMTKHPAKR LGCGPEGERD VREHAFFRRI 

       610        620        630        640        650        660 
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVLTPP DQLVIANIDQ SDFEGFSYVN 

       670 
PQFVHPILQS AV 

« Hide

References

« Hide 'large scale' references
[1]"Sequence of human protein kinase C alpha."
Finkenzeller G., Marme D., Hug H.
Nucleic Acids Res. 18:2183-2183(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-568.
Tissue: Blood.
[2]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-568.
[3]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-568.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-568.
[6]"Phorbol diester-induced alterations in the expression of protein kinase C isozymes and their mRNAs. Analysis in wild-type and phorbol diester-resistant HL-60 cell clones."
McSwine-Kennick R.L., McKeegan E.M., Johnson M.D., Morin M.J.
J. Biol. Chem. 266:15135-15143(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-445.
[7]"Homo sapiens protein kinase C alpha 5-flanking sequence."
Haridasse V., Hackenbruck J., Glazer R.I.
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-57.
[8]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-19.
Tissue: Platelet.
[9]"A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis."
Ruvolo P.P., Deng X., Carr B.K., May W.S.
J. Biol. Chem. 273:25436-25442(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION.
[10]"Protein kinase C-alpha modulates lipopolysaccharide-induced functions in a murine macrophage cell line."
St-Denis A., Chano F., Tremblay P., St-Pierre Y., Descoteaux A.
J. Biol. Chem. 273:32787-32792(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
[11]"Interleukin-1-induced nuclear factor-kappaB-IkappaBalpha autoregulatory feedback loop in hepatocytes. A role for protein kinase calpha in post-transcriptional regulation of ikappabalpha resynthesis."
Han Y., Meng T., Murray N.R., Fields A.P., Brasier A.R.
J. Biol. Chem. 274:939-947(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
[12]"Induction of p53-dependent, insulin-like growth factor-binding protein-3-mediated apoptosis in glioblastoma multiforme cells by a protein kinase Calpha antisense oligonucleotide."
Shen L., Dean N.M., Glazer R.I.
Mol. Pharmacol. 55:396-402(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS.
[13]"Involvement of p21(Waf1/Cip1) in protein kinase C alpha-induced cell cycle progression."
Besson A., Yong V.W.
Mol. Cell. Biol. 20:4580-4590(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL CYCLE PROGRESSION.
[14]"Inhibition of protein kinase Calpha prevents endothelial cell migration and vascular tube formation in vitro and myocardial neovascularization in vivo."
Wang A., Nomura M., Patan S., Ware J.A.
Circ. Res. 90:609-616(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS.
[15]"Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C."
Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D., Wakefield R.I.D., Johannes F.-J., Aitken A.
Biochem. Biophys. Res. Commun. 307:459-465(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADAP1.
[16]"Direct demonstration of involvement of protein kinase Calpha in the Ca2+-induced platelet aggregation."
Tabuchi A., Yoshioka A., Higashi T., Shirakawa R., Nishioka H., Kita T., Horiuchi H.
J. Biol. Chem. 278:26374-26379(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELET AGGREGATION.
[17]"Identification of a functionally critical protein kinase C phosphorylation residue of cardiac troponin T."
Sumandea M.P., Pyle W.G., Kobayashi T., de Tombe P.P., Solaro R.J.
J. Biol. Chem. 278:35135-35144(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TNNT2/CTNT.
[18]"Signal transduction via the stem cell factor receptor/c-Kit."
Ronnstrand L.
Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN KIT SIGNALING.
[19]"Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells."
Ahmmed G.U., Mehta D., Vogel S., Holinstat M., Paria B.C., Tiruppathi C., Malik A.B.
J. Biol. Chem. 279:20941-20949(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TRPC1.
[20]"The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands."
Dev K.K., Nakanishi S., Henley J.M.
J. Biol. Chem. 279:41393-41397(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PICK1.
[21]"Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates polarized membrane distribution and cell motility."
Makagiansar I.T., Williams S., Dahlin-Huppe K., Fukushi J., Mustelin T., Stallcup W.B.
J. Biol. Chem. 279:55262-55270(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CSPG4, INTERACTION WITH CSPG4.
[22]"Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
Roskoski R. Jr.
Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[23]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"Amplitude control of protein kinase C by RINCK, a novel E3 ubiquitin ligase."
Chen D., Gould C., Garza R., Gao T., Hampton R.Y., Newton A.C.
J. Biol. Chem. 282:33776-33787(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM41.
[25]"Protein kinase C alpha promotes angiogenic activity of human endothelial cells via induction of vascular endothelial growth factor."
Xu H., Czerwinski P., Hortmann M., Sohn H.Y., Foerstermann U., Li H.
Cardiovasc. Res. 78:349-355(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS.
[26]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[27]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-638 AND SER-651, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[29]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[30]"Phosphorylation of activation transcription factor-2 at serine 121 by protein kinase c controls c-Jun-mediated activation of transcription."
Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K.
J. Biol. Chem. 284:8567-8581(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[31]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[32]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-628, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND THR-638, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[34]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1) by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1."
Dobrikov M., Dobrikova E., Shveygert M., Gromeier M.
Mol. Cell. Biol. 31:2947-2959(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EIF4G1.
[36]"Protein kinase C alpha (PKC alpha): regulation and biological function."
Nakashima S.
J. Biochem. 132:669-675(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[37]"Protein kinase Calpha: disease regulator and therapeutic target."
Konopatskaya O., Poole A.W.
Trends Pharmacol. Sci. 31:8-14(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[38]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[39]"Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration."
Evensen N.A., Kuscu C., Nguyen H.L., Zarrabi K., Dufour A., Kadam P., Hu Y.J., Pulkoski-Gross A., Bahou W.F., Zucker S., Cao J.
J. Natl. Cancer Inst. 105:1402-1416(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION.
[40]"Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes."
Wagner J., von Matt P., Sedrani R., Albert R., Cooke N., Ehrhardt C., Geiser M., Rummel G., Stark W., Strauss A., Cowan-Jacob S.W., Beerli C., Weckbecker G., Evenou J.P., Zenke G., Cottens S.
J. Med. Chem. 52:6193-6196(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 320-672 IN COMPLEX WITH INHIBITOR.
[41]"Solution structure of the second phorbol esters/diacylglycerol binding domain of human protein kinase C alpha type."
RIKEN structural genomics initiative (RSGI)
Submitted (APR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 88-169.
[42]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-98; ASN-467 AND VAL-489.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52479 mRNA. Translation: CAA36718.1.
AB451258 mRNA. Translation: BAG70072.1.
AB451383 mRNA. Translation: BAG70197.1.
AC005918 Genomic DNA. No translation available.
AC005988 Genomic DNA. No translation available.
AC006263 Genomic DNA. No translation available.
AC006947 Genomic DNA. No translation available.
AC009452 Genomic DNA. No translation available.
AC060796 Genomic DNA. No translation available.
CH471099 Genomic DNA. Translation: EAW89014.1.
BC109273 mRNA. Translation: AAI09274.1.
BC109274 mRNA. Translation: AAI09275.1.
M22199 mRNA. Translation: AAA60098.1.
AF395829 Genomic DNA. Translation: AAK84184.1.
CCDSCCDS11664.1.
PIRKIHUCA. S09496.
RefSeqNP_002728.1. NM_002737.2.
UniGeneHs.531704.
Hs.708867.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ELINMR-A93-169[»]
3IW4X-ray2.80A/B/C320-672[»]
4DNLX-ray1.90A155-293[»]
ProteinModelPortalP17252.
SMRP17252. Positions 37-670.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111564. 104 interactions.
DIPDIP-531N.
IntActP17252. 25 interactions.
MINTMINT-140812.
STRING9606.ENSP00000284384.

Chemistry

BindingDBP17252.
ChEMBLCHEMBL2096620.
DrugBankDB00144. Phosphatidylserine.
DB00163. Vitamin E.
GuidetoPHARMACOLOGY1482.

PTM databases

PhosphoSiteP17252.

Polymorphism databases

DMDM317373571.

Proteomic databases

MaxQBP17252.
PaxDbP17252.
PRIDEP17252.

Protocols and materials databases

DNASU5578.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000413366; ENSP00000408695; ENSG00000154229.
GeneID5578.
KEGGhsa:5578.
UCSCuc002jfo.1. human.

Organism-specific databases

CTD5578.
GeneCardsGC17P064298.
HGNCHGNC:9393. PRKCA.
HPACAB003844.
CAB016290.
HPA006563.
HPA006564.
MIM176960. gene.
neXtProtNX_P17252.
PharmGKBPA33759.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidP17252.
KOK02677.
OMAPQFVHPL.
OrthoDBEOG77M8QM.
PhylomeDBP17252.
TreeFamTF351133.

Enzyme and pathway databases

BRENDA2.7.11.13. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_13685. Neuronal System.
REACT_21257. Metabolism of RNA.
REACT_21300. Mitotic M-M/G1 phases.
REACT_604. Hemostasis.
REACT_6900. Immune System.
REACT_71. Gene Expression.
SignaLinkP17252.

Gene expression databases

ArrayExpressP17252.
BgeeP17252.
CleanExHS_PRKACA.
HS_PRKCA.
GenevestigatorP17252.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014375. Protein_kinase_C_a/b/g.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000550. PKC_alpha. 1 hit.
PRINTSPR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKCA. human.
EvolutionaryTraceP17252.
GeneWikiPKC_alpha.
GenomeRNAi5578.
NextBio21628.
PMAP-CutDBP17252.
PROP17252.
SOURCESearch...

Entry information

Entry nameKPCA_HUMAN
AccessionPrimary (citable) accession number: P17252
Secondary accession number(s): B5BU22 expand/collapse secondary AC list , Q15137, Q32M72, Q96RE4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 171 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM