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Names & Taxonomy

Uniprot ID:: P17252
Entry Name:: KPCA_HUMAN
Status:: reviewed
Protein Names:: Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13)
Gene Names:: PRKCA PKCA PRKACA
Gene Names Primary:: PRKCA
Organism:: Homo sapiens (Human)

Structure

Length:: 672
Sequence:: MADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm

Function

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.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Cofactor:: COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
Enzyme Regulation:: 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.
Active Site:: ACT_SITE 463 463 Proton acceptor.
Cross Reference Drug Bank:: DB05013 DB00144 DB00675 DB00163
Gene Ontology Go:: cytoplasm
cytosol
endoplasmic reticulum
extracellular exosome
mitochondrial membrane
mitochondrion
nucleoplasm
perinuclear region of cytoplasm
plasma membrane
ATP binding
enzyme binding
histone kinase activity (H3-T6 specific)
protein kinase activity
protein kinase C activity
protein serine/threonine kinase activity
zinc ion binding
activation of adenylate cyclase activity
activation of phospholipase C activity
angiogenesis
apoptotic signaling pathway
blood coagulation
cell adhesion
desmosome assembly
energy reserve metabolic process
epidermal growth factor receptor signaling pathway
extracellular matrix organization
fibroblast growth factor receptor signaling pathway
gene expression
histone H3-T6 phosphorylation
innate immune response
intracellular signal transduction
mitotic cell cycle
mitotic nuclear envelope disassembly
negative regulation of adenylate cyclase activity
negative regulation of glial cell apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
phototransduction, visible light
platelet activation
positive regulation of angiogenesis
positive regulation of blood vessel endothelial cell migration
positive regulation of cardiac muscle hypertrophy
positive regulation of cell adhesion
positive regulation of cell migration
positive regulation of dense core granule biogenesis
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of lipopolysaccharide-mediated signaling pathway
positive regulation of macrophage differentiation
positive regulation of mitotic cell cycle
protein phosphorylation
regulation of insulin secretion
regulation of mRNA stability
regulation of platelet aggregation
regulation of rhodopsin mediated signaling pathway
response to interleukin-1
rhodopsin mediated signaling pathway
signal transduction
small molecule metabolic process
synaptic transmission
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:: activation of adenylate cyclase activity
activation of phospholipase C activity
angiogenesis
apoptotic signaling pathway
blood coagulation
cell adhesion
desmosome assembly
energy reserve metabolic process
epidermal growth factor receptor signaling pathway
extracellular matrix organization
fibroblast growth factor receptor signaling pathway
gene expression
histone H3-T6 phosphorylation
innate immune response
intracellular signal transduction
mitotic cell cycle
mitotic nuclear envelope disassembly
negative regulation of adenylate cyclase activity
negative regulation of glial cell apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
phototransduction, visible light
platelet activation
positive regulation of angiogenesis
positive regulation of blood vessel endothelial cell migration
positive regulation of cardiac muscle hypertrophy
positive regulation of cell adhesion
positive regulation of cell migration
positive regulation of dense core granule biogenesis
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of lipopolysaccharide-mediated signaling pathway
positive regulation of macrophage differentiation
positive regulation of mitotic cell cycle
protein phosphorylation
regulation of insulin secretion
regulation of mRNA stability
regulation of platelet aggregation
regulation of rhodopsin mediated signaling pathway
response to interleukin-1
rhodopsin mediated signaling pathway
signal transduction
small molecule metabolic process
synaptic transmission
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:: ATP binding
enzyme binding
histone kinase activity (H3-T6 specific)
protein kinase activity
protein kinase C activity
protein serine/threonine kinase activity
zinc ion binding
Gene Ontology Cellular Component:: cytoplasm
cytosol
endoplasmic reticulum
extracellular exosome
mitochondrial membrane
mitochondrion
nucleoplasm
perinuclear region of cytoplasm
plasma membrane
Keywords:: 3D-structure
ATP-binding
Acetylation
Angiogenesis
Apoptosis
Calcium
Cell adhesion
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Kinase
Membrane
Metal-binding
Mitochondrion
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger
Interacts With:: P00533; Q9UBN7; Q24008; P31431; P0CG48

Names & Taxonomy

Structure

Subcellular location

Function

Publication