P17252 (KPCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	672 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.24 Ref.32
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.19 Ref.20 Ref.23
Subcellular location	Cytoplasm. Cell membrane; Peripheral membrane protein. Mitochondrion membrane; Peripheral membrane protein Probable. Nucleus Ref.9.
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 process	Angiogenesis Apoptosis Cell adhesion
Cellular component	Cell membrane Cytoplasm Membrane Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	ATP-binding Calcium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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 cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara cellular response to carbohydrate stimulus Inferred from electronic annotation. Source: Compara chondrocyte differentiation Inferred from electronic annotation. Source: Compara 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 fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome gene expression Traceable author statement. Source: Reactome inactivation of MAPK activity Inferred from electronic annotation. Source: Compara induction of positive chemotaxis Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of insulin receptor signaling pathway Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome neutrophil chemotaxis Inferred from electronic annotation. Source: Compara 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 dense core granule biogenesis Inferred from sequence or structural similarity. 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: Compara 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: Compara regulation of insulin secretion Traceable author statement. Source: Reactome regulation of muscle contraction Inferred from electronic annotation. Source: Compara regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara regulation of platelet aggregation Inferred from direct assay Ref.16. Source: UniProtKB regulation of the force of heart contraction Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from mutant phenotype PubMed 19281832. Source: BHF-UCL small molecule metabolic process Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from direct assay PubMed 17983652. Source: UniProtKB dendrite Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from direct assay PubMed 18556656. Source: BHF-UCL mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell neuronal cell body Inferred from electronic annotation. Source: Compara 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: Compara plasma membrane Inferred from direct assay PubMed 15632189. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-dependent protein kinase C activity Inferred from electronic annotation. Source: Compara histone kinase activity (H3-T6 specific) Inferred from direct assay PubMed 20228790. Source: UniProtKB protein kinase C activity Inferred from sequence or structural similarity. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
inaD	Q24008	2	EBI-1383528,EBI-195326	From a different organism.
SDC4	P31431	2	EBI-1383528,EBI-3913237

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 672

671

Protein kinase C alpha type

PRO_0000055679

Regions

Domain

172 – 260

89

C2

Domain

339 – 597

259

Protein kinase

Domain

598 – 668

71

AGC-kinase C-terminal

Zinc finger

36 – 86

51

Phorbol-ester/DAG-type 1

Zinc finger

101 – 151

51

Phorbol-ester/DAG-type 2

Nucleotide binding

345 – 353

9

ATP By similarity

Sites

Active site

463

1

Proton acceptor By similarity

Metal binding

186

1

Calcium 1; via carbonyl oxygen By similarity

Metal binding

187

1

Calcium 1 By similarity

Metal binding

187

1

Calcium 2 By similarity

Metal binding

193

1

Calcium 2 By similarity

Metal binding

246

1

Calcium 1 By similarity

Metal binding

246

1

Calcium 2 By similarity

Metal binding

247

1

Calcium 2; via carbonyl oxygen By similarity

Metal binding

248

1

Calcium 1 By similarity

Metal binding

248

1

Calcium 2 By similarity

Metal binding

248

1

Calcium 3 By similarity

Metal binding

252

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

254

1

Calcium 1 By similarity

Metal binding

254

1

Calcium 3 By similarity

Binding site

195

1

Inositol phosphate group By similarity

Binding site

245

1

Inositol phosphate group By similarity

Binding site

368

1

ATP By similarity

Amino acid modifications

Modified residue

226

1

Phosphoserine Ref.27 Ref.28 Ref.30

Modified residue

250

1

Phosphothreonine; by autocatalysis

Modified residue

319

1

Phosphoserine By similarity

Modified residue

497

1

Phosphothreonine; by PDPK1 Probable

Modified residue

628

1

N6-acetyllysine Ref.29

Modified residue

631

1

Phosphothreonine; by autocatalysis Potential

Modified residue

638

1

Phosphothreonine; by autocatalysis Ref.26 Ref.30

Modified residue

651

1

Phosphoserine Ref.26

Modified residue

657

1

Phosphoserine By similarity

Modified residue

658

1

Phosphotyrosine; by SYK By similarity

Natural variations

Natural variant

98

1

P → S in a colorectal adenocarcinoma sample; somatic mutation. Ref.37

VAR_042301

Natural variant

467

1

D → N in a glioblastoma multiforme sample; somatic mutation. Ref.37

VAR_042302

Natural variant

489

1

M → V. Ref.37
Corresponds to variant rs34406842 [ dbSNP | Ensembl ].

VAR_042303

Natural variant

568

1

V → I. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs6504459 [ dbSNP | Ensembl ].

VAR_050558

Experimental info

Sequence conflict

50

1

C → S in AAA60098. Ref.6

Secondary structure

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672

Helix Strand Turn

Details...

Turn

98 – 100

3

Beta strand

105 – 107

3

Beta strand

116 – 118

3

Beta strand

125 – 127

3

Beta strand

129 – 131

3

Beta strand

133 – 135

3

Beta strand

138 – 140

3

Turn

141 – 146

6

Beta strand

161 – 169

9

Beta strand

172 – 182

11

Beta strand

194 – 202

9

Beta strand

222 – 230

9

Helix

233 – 237

5

Beta strand

239 – 246

8

Beta strand

249 – 251

3

Beta strand

254 – 262

9

Helix

263 – 268

6

Beta strand

271 – 276

6

Helix

282 – 284

3

Helix

336 – 338

3

Beta strand

339 – 348

10

Beta strand

351 – 358

8

Beta strand

364 – 371

8

Helix

372 – 377

6

Helix

381 – 392

12

Beta strand

403 – 408

6

Beta strand

410 – 418

9

Beta strand

422 – 424

3

Helix

425 – 432

8

Helix

437 – 456

20

Helix

466 – 468

3

Beta strand

469 – 471

3

Beta strand

477 – 479

3

Helix

502 – 504

3

Helix

507 – 510

4

Helix

518 – 533

16

Helix

543 – 552

10

Helix

563 – 572

10

Turn

577 – 579

3

Helix

587 – 592

6

Helix

595 – 597

3

Helix

602 – 605

4

Turn

606 – 608

3

Helix

642 – 646

5

Helix

650 – 653

4

Sequences

	Sequence		Length	Mass (Da)
	P17252 [UniParc]. Last modified January 11, 2011. Version 4. Checksum: 9EB157789A062349	FASTA	672	76,750
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[29]	"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, MASS SPECTROMETRY.
[30]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[31]	"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].
[32]	"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.
[33]	"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.
[34]	"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.
[35]	"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.
[36]	"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.
[37]	"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. , 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.

IPI

IPI00385449.

PIR

KIHUCA. S09496.

RefSeq

NP_002728.1. NM_002737.2.

UniGene

Hs.531704.
Hs.708867.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ELI	NMR	-	A	92-169	[»]
3IW4	X-ray	2.80	A/B/C	320-672	[»]
4DNL	X-ray	1.90	A	155-293	[»]

ProteinModelPortal

P17252.

SMR

P17252. Positions 37-670.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-531N.

IntAct

P17252. 9 interactions.

MINT

MINT-140812.

STRING

9606.ENSP00000284384.

PTM databases

PhosphoSite

P17252.

Polymorphism databases

DMDM

125549.

Proteomic databases

PaxDb

P17252.

PRIDE

P17252.

Protocols and materials databases

DNASU

5578.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000413366; ENSP00000408695; ENSG00000154229.

GeneID

5578.

KEGG

hsa:5578.

UCSC

uc002jfo.1. human.

Organism-specific databases

CTD

5578.

GeneCards

GC17P064298.

HGNC

HGNC:9393. PRKCA.

HPA

CAB003844.
CAB016290.
HPA006563.
HPA006564.

MIM

176960. gene.

neXtProt

NX_P17252.

PharmGKB

PA33759.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233022.

HOVERGEN

HBG108317.

InParanoid

P17252.

KO

K02677.

OMA

HEYVTFI.

OrthoDB

EOG40ZQX0.

PhylomeDB

P17252.

Enzyme and pathway databases

BRENDA

2.7.11.13. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
syndecan_4_pathway. Syndecan-4-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
txa2pathway. Thromboxane A2 receptor signaling.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_21257. Metabolism of RNA.
REACT_604. Hemostasis.
REACT_6900. Immune System.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P17252.

Bgee

P17252.

CleanEx

HS_PRKACA.
HS_PRKCA.

Genevestigator

P17252.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR020477. C2_dom.
IPR018029. C2_membr_targeting.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_cat_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]

Pfam

PF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000550. PKC_alpha. 1 hit.

PRINTS

PR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS51285. 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]

ProtoNet

Search...

Other

BindingDB

P17252.

ChEMBL

CHEMBL299.

ChiTaRS

PRKCA. human.

DrugBank

DB00144. Phosphatidylserine.
DB00163. Vitamin E.

EvolutionaryTrace

P17252.

GenomeRNAi

5578.

NextBio

21628.

PMAP-CutDB

P17252.

SOURCE

Search...

Entry information

Entry name

KPCA_HUMAN

Accession

Primary (citable) accession number: P17252
Secondary accession number(s): B5BU22 , Q15137, Q32M72, Q96RE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 11, 2011
Last modified:	April 3, 2013
This is version 158 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.