Protein kinase C alpha type - Bos taurus (Bovine)

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P04409 (KPCA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 138. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

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, 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. Depending on the cell type, is 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 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. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or 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. 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 By similarity.
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	Interacts with ADAP1/CENTA1, CSPG4 and PRKCABP. Binds to SDPR in the presence of phosphatidylserine By similarity. Interacts with PICK1 (via PDZ domain) By similarity. Interacts with TRIM41 By similarity. Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and GNB2L1/RACK1 By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane; Peripheral membrane protein By similarity. Mitochondrion membrane; Peripheral membrane protein By similarity. Nucleus By similarity.
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
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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Inferred from direct assay PubMed 8900209. Source: BHF-UCL angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of adenylate cyclase activity Inferred from direct assay PubMed 8900209. Source: BHF-UCL negative regulation of glial cell apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cardiac muscle hypertrophy Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell adhesion Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB positive regulation of endothelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of lipopolysaccharide-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of macrophage differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB regulation of platelet aggregation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from direct assay PubMed 8900209. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 672

671

Protein kinase C alpha type

PRO_0000055678

Regions

Domain

172 – 260

Domain

339 – 597

259

Protein kinase

Domain

598 – 668

AGC-kinase C-terminal

Zinc finger

36 – 86

Phorbol-ester/DAG-type 1

Zinc finger

101 – 151

Phorbol-ester/DAG-type 2

Nucleotide binding

345 – 353

ATP By similarity

Sites

Active site

463

Proton acceptor By similarity

Metal binding

186

Calcium 1; via carbonyl oxygen By similarity

Metal binding

187

Calcium 1 By similarity

Metal binding

187

Calcium 2 By similarity

Metal binding

193

Calcium 2 By similarity

Metal binding

246

Calcium 1 By similarity

Metal binding

246

Calcium 2 By similarity

Metal binding

247

Calcium 2; via carbonyl oxygen By similarity

Metal binding

248

Calcium 1 By similarity

Metal binding

248

Calcium 2 By similarity

Metal binding

248

Calcium 3 By similarity

Metal binding

252

Calcium 3; via carbonyl oxygen By similarity

Metal binding

254

Calcium 1 By similarity

Metal binding

254

Calcium 3 By similarity

Binding site

195

Inositol phosphate group By similarity

Binding site

245

Inositol phosphate group By similarity

Binding site

368

ATP By similarity

Amino acid modifications

Modified residue

226

Phosphoserine By similarity

Modified residue

250

Phosphothreonine; by autocatalysis By similarity

Modified residue

319

Phosphoserine By similarity

Modified residue

494

Phosphothreonine Probable

Modified residue

495

Phosphothreonine Probable

Modified residue

497

Phosphothreonine; by PDPK1 Probable

Modified residue

628

N6-acetyllysine By similarity

Modified residue

631

Phosphothreonine; by autocatalysis Potential

Modified residue

638

Phosphothreonine; by autocatalysis By similarity

Modified residue

651

Phosphoserine By similarity

Modified residue

657

Phosphoserine Ref.4

Modified residue

658

Phosphotyrosine; by SYK By similarity

Experimental info

Mutagenesis

494

T → A: Abolishes phosphorylation and catalytic activity; when associated with A-495 and A-497. Ref.3

Mutagenesis

495

T → A: Abolishes phosphorylation and catalytic activity; when associated with A-494 and A-497. Ref.3

Mutagenesis

497

T → A: Abolishes phosphorylation and catalytic activity; when associated with A-494 and A-495. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

P04409 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 97BF46DB80FCF21A
Show »

FASTA

672

76,837

        10         20         30         40         50         60 
MADVFPAAEP AAPQDVANRF ARKGALRQKN VHEVKNHRFI ARFFKQPTFC SHCTDFIWGF 

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

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

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

       250        260        270        280        290        300 
SEEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKLLNQ EEGEYYNVPI PEGDEEGNVE 

       310        320        330        340        350        360 
LRQKFEKAKL GPAGNKVISP SEDRRQPSNN 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 LSKEAVSICK GLMTKHPGKR LGCGPEGERD VREHAFFRRI 

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

       670 
PQFVHPILQS AV

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References

[1]	"The complete primary structure of protein kinase C -- the major phorbol ester receptor." Parker P.J., Coussens L., Totty N., Rhee L., Young S., Chen E., Stabel S., Waterfield M.D., Ullrich A. Science 233:853-859(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The molecular heterogeneity of protein kinase C and its implications for cellular regulation." Nishizuka Y. Nature 334:661-665(1988) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[3]	"Identification of the phosphorylated region responsible for the permissive activation of protein kinase C." Cazaubon S.M., Parker P.J. J. Biol. Chem. 268:17559-17563(1993) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF THR-494; THR-495 AND THR-497, PHOSPHORYLATION AT THR-494; THR-495 AND THR-497.
[4]	"Phosphorylation of protein kinase C-alpha on serine 657 controls the accumulation of active enzyme and contributes to its phosphatase-resistant state." Bornancin F., Parker P.J. J. Biol. Chem. 272:3544-3549(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-657.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M13973 mRNA. Translation: AAA30706.1.
IPI	IPI00695208.
PIR	KIBOC. A00621.
RefSeq	NP_776860.1. NM_174435.1.
UniGene	Bt.62458.
3D structure databases
ProteinModelPortal	P04409.
SMR	P04409. Positions 37-292, 336-666.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-530N.
MINT	MINT-1529738.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	282001.
KEGG	bta:282001.
Organism-specific databases
CTD	5578.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233022.
HOVERGEN	HBG108317.
InParanoid	P04409.
KO	K02677.
OrthoDB	EOG40ZQX0.
Enzyme and pathway databases
BioCyc	CATTLE:282001-MONOMER.
BRENDA	2.7.11.13. 908.
Reactome	REACT_114534. Signal Transduction.
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	P04409.
ChEMBL	CHEMBL2213.
NextBio	20805869.

Entry information

Entry name

KPCA_BOVIN

Accession

Primary (citable) accession number: P04409

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Other

Entry information

Relevant documents