Gene/Proteome Database (LMPD)

LMPD ID
LMP001411
Gene ID
5578
Species
Homo sapiens (Human)
Gene Name
protein kinase C, alpha
Gene Symbol
PRKCA
Synonyms
AAG6; PKC-alpha; PKCA; PRKACA
Alternate Names
protein kinase C alpha type; PKC-A; aging-associated gene 6
Chromosome
17
Map Location
17q22-q23.2
EC Number
2.7.11.13
Summary
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for PRKCA

Proteins

protein kinase C alpha type
Refseq ID NP_002728
Protein GI 4506067
UniProt ID P17252
mRNA ID NM_002737
Length 672
RefSeq Status REVIEWED
MADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSICKGLMTKHPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV

Gene Information

Entrez Gene ID
5578
Gene Name
protein kinase C, alpha
Gene Symbol
PRKCA
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0045177 IEA:Ensembl C apical part of cell
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0005829 IDA:UniProtKB C cytosol
GO:0030425 IEA:Ensembl C dendrite
GO:0005783 IDA:BHF-UCL C endoplasmic reticulum
GO:0070062 IDA:UniProt C extracellular vesicular exosome
GO:0005739 IDA:UniProt C mitochondrion
GO:0043025 IEA:Ensembl C neuronal cell body
GO:0005654 TAS:Reactome C nucleoplasm
GO:0048471 ISS:UniProtKB C perinuclear region of cytoplasm
GO:0001750 IEA:Ensembl C photoreceptor outer segment
GO:0005886 IDA:UniProtKB C plasma membrane
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0004698 IEA:Ensembl F calcium-dependent protein kinase C activity
GO:0019899 IDA:BHF-UCL F enzyme binding
GO:0035403 IDA:UniProtKB F histone kinase activity (H3-T6 specific)
GO:0004697 ISS:BHF-UCL F protein kinase C activity
GO:0004672 IDA:UniProtKB F protein kinase activity
GO:0008270 IEA:InterPro F zinc ion binding
GO:0016070 TAS:Reactome P RNA metabolic process
GO:0007190 ISS:BHF-UCL P activation of adenylate cyclase activity
GO:0007202 TAS:Reactome P activation of phospholipase C activity
GO:0001525 IEA:UniProtKB-KW P angiogenesis
GO:0097190 TAS:ProtInc P apoptotic signaling pathway
GO:0007596 TAS:Reactome P blood coagulation
GO:0007155 IEA:UniProtKB-KW P cell adhesion
GO:0006874 IEA:Ensembl P cellular calcium ion homeostasis
GO:0071322 IEA:Ensembl P cellular response to carbohydrate stimulus
GO:0002062 IEA:Ensembl P chondrocyte differentiation
GO:0002159 IMP:BHF-UCL P desmosome assembly
GO:0006112 TAS:Reactome P energy reserve metabolic process
GO:0007173 TAS:Reactome P epidermal growth factor receptor signaling pathway
GO:0030198 TAS:Reactome P extracellular matrix organization
GO:0008543 TAS:Reactome P fibroblast growth factor receptor signaling pathway
GO:0010467 TAS:Reactome P gene expression
GO:0035408 IDA:UniProtKB P histone H3-T6 phosphorylation
GO:0000188 IEA:Ensembl P inactivation of MAPK activity
GO:0050930 IEA:Ensembl P induction of positive chemotaxis
GO:0045087 TAS:Reactome P innate immune response
GO:0097193 IEA:Ensembl P intrinsic apoptotic signaling pathway
GO:0016071 TAS:Reactome P mRNA metabolic process
GO:0007194 ISS:BHF-UCL P negative regulation of adenylate cyclase activity
GO:0008285 IEA:Ensembl P negative regulation of cell proliferation
GO:0034351 IMP:UniProtKB P negative regulation of glial cell apoptotic process
GO:0046325 IEA:Ensembl P negative regulation of glucose import
GO:0046627 IEA:Ensembl P negative regulation of insulin receptor signaling pathway
GO:0048011 TAS:Reactome P neurotrophin TRK receptor signaling pathway
GO:0030593 IEA:Ensembl P neutrophil chemotaxis
GO:0036289 IEA:Ensembl P peptidyl-serine autophosphorylation
GO:0007603 TAS:Reactome P phototransduction, visible light
GO:0030168 TAS:Reactome P platelet activation
GO:0070374 ISS:UniProtKB P positive regulation of ERK1 and ERK2 cascade
GO:0045766 IMP:UniProtKB P positive regulation of angiogenesis
GO:0043536 IDA:DFLAT P positive regulation of blood vessel endothelial cell migration
GO:0010613 ISS:UniProtKB P positive regulation of cardiac muscle hypertrophy
GO:0045785 IMP:UniProtKB P positive regulation of cell adhesion
GO:0030335 IMP:UniProtKB P positive regulation of cell migration
GO:2000707 ISS:UniProtKB P positive regulation of dense core granule biogenesis
GO:0010595 IMP:UniProtKB P positive regulation of endothelial cell migration
GO:0001938 IMP:UniProtKB P positive regulation of endothelial cell proliferation
GO:0050729 IEA:Ensembl P positive regulation of inflammatory response
GO:0031666 IMP:UniProtKB P positive regulation of lipopolysaccharide-mediated signaling pathway
GO:0045651 ISS:UniProtKB P positive regulation of macrophage differentiation
GO:0045931 IMP:UniProtKB P positive regulation of mitotic cell cycle
GO:0001934 IEA:Ensembl P positive regulation of protein phosphorylation
GO:0006468 IDA:UniProtKB P protein phosphorylation
GO:0050796 TAS:Reactome P regulation of insulin secretion
GO:0006937 IEA:Ensembl P regulation of muscle contraction
GO:0050730 IEA:Ensembl P regulation of peptidyl-tyrosine phosphorylation
GO:0090330 IDA:UniProtKB P regulation of platelet aggregation
GO:0022400 TAS:Reactome P regulation of rhodopsin mediated signaling pathway
GO:0002026 IEA:Ensembl P regulation of the force of heart contraction
GO:0070555 IMP:BHF-UCL P response to interleukin-1
GO:0016056 TAS:Reactome P rhodopsin mediated signaling pathway
GO:0007165 TAS:Reactome P signal transduction
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0007268 TAS:Reactome P synaptic transmission

KEGG Pathway Links

KEGG Pathway ID Description
hsa04261 Adrenergic signaling in cardiomyocytes
hsa04750 Inflammatory mediator regulation of TRP channels
hsa04921 Oxytocin signaling pathway
hsa04919 Thyroid hormone signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR000961 AGC-kinase, C-terminal
IPR000008 C2 domain
IPR020454 Diacylglycerol/phorbol-ester binding
IPR014375 Protein kinase C, alpha/beta/gamma types
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR000719 Protein kinase domain
IPR017441 Protein kinase, ATP binding site
IPR017892 Protein kinase, C-terminal
IPR011009 Protein kinase-like domain
IPR008271 Serine/threonine-protein kinase, active site
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain

UniProt Annotations

Entry Information

Gene Name
protein kinase C, alpha
Protein Entry
KPCA_HUMAN
UniProt ID
P17252
Species
Human

Comments

Comment Type Description
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Cofactor Name=Ca(2+); Xref=ChEBI
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.
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. {ECO
Interaction P00533:EGFR; NbExp=2; IntAct=EBI-1383528, EBI-297353; Q9UBN7:HDAC6; NbExp=2; IntAct=EBI-1383528, EBI-301697; Q24008:inaD (xeno); NbExp=2; IntAct=EBI-1383528, EBI-195326; P31431:SDC4; NbExp=2; IntAct=EBI-1383528, EBI-3913237; P0CG48:UBC; NbExp=2; IntAct=EBI-1383528, EBI-3390054;
Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Similarity Contains 1 AGC-kinase C-terminal domain.
Similarity Contains 1 C2 domain. {ECO
Similarity Contains 1 protein kinase domain.
Similarity Contains 2 phorbol-ester/DAG-type zinc fingers.
Subcellular Location Cytoplasm. Cell membrane; Peripheral membrane protein. Mitochondrion membrane ; Peripheral membrane protein . Nucleus.
Subunit 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. {ECO

Identical and Related Proteins

Unique RefSeq proteins for LMP001411 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
4506067 RefSeq NP_002728 672 protein kinase C alpha type

Identical Sequences to LMP001411 proteins

Reference Database Accession Length Protein Name
GI:4506067 GenBank ADM03569.1 672 Sequence 164 from patent US 7727958
GI:4506067 GenBank ADS40177.1 672 Sequence 120 from patent US 7792665
GI:4506067 GenBank AGV86227.1 672 Sequence 164 from patent US 8524673
GI:4506067 GenBank AHD71835.1 672 Sequence 6529 from patent US 8586006
GI:4506067 GenBank AIC49474.1 672 PRKCA, partial [synthetic construct]
GI:4506067 RefSeq XP_004041162.1 672 PREDICTED: protein kinase C alpha type [Gorilla gorilla gorilla]

Related Sequences to LMP001411 proteins

Reference Database Accession Length Protein Name
GI:4506067 GenBank AAX36750.1 673 protein kinase C alpha, partial [synthetic construct]
GI:4506067 GenBank AGC09604.1 672 protein kinase C, alpha [Homo sapiens]
GI:4506067 RefSeq XP_002919986.1 152 PREDICTED: tyrosine-protein kinase Fer-like [Ailuropoda melanoleuca]
GI:4506067 RefSeq XP_003415462.1 745 PREDICTED: LOW QUALITY PROTEIN: ribosomal protein S6 kinase alpha-1-like [Loxodonta africana]
GI:4506067 RefSeq XP_008010230.1 672 PREDICTED: protein kinase C alpha type isoform X1 [Chlorocebus sabaeus]
GI:4506067 SwissProt P17252.4 672 RecName: Full=Protein kinase C alpha type; Short=PKC-A; Short=PKC-alpha [Homo sapiens]