Gene/Proteome Database (LMPD)

LMPD ID
LMP000331
Gene ID
18750
Species
Mus musculus (Mouse)
Gene Name
protein kinase C, alpha
Gene Symbol
Prkca
Synonyms
AI875142; Pkca
Alternate Names
protein kinase C alpha type; PKC-A; PKC-alpha; protein kinase c-alpha
Chromosome
11
Map Location
11 E1|11 70.8 cM
EC Number
2.7.11.13

Proteins

protein kinase C alpha type
Refseq ID NP_035231
Protein GI 164663791
UniProt ID P20444
mRNA ID NM_011101
Length 672
RefSeq Status VALIDATED
MADVYPANDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVTDEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSICKGLMTKHPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV

Gene Information

Entrez Gene ID
18750
Gene Name
protein kinase C, alpha
Gene Symbol
Prkca
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0045177 IDA:MGI C apical part of cell
GO:0005737 IDA:MGI C cytoplasm
GO:0030425 IDA:MGI C dendrite
GO:0005739 IDA:MGI C mitochondrion
GO:0043025 IDA:MGI C neuronal cell body
GO:0005634 IDA:MGI C nucleus
GO:0048471 ISS:UniProtKB C perinuclear region of cytoplasm
GO:0001750 IDA:MGI C photoreceptor outer segment
GO:0005886 IDA:MGI C plasma membrane
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0004698 IDA:MGI F calcium-dependent protein kinase C activity
GO:0004697 IDA:MGI F protein kinase C activity
GO:0004674 IDA:MGI F protein serine/threonine kinase activity
GO:0008270 IEA:InterPro F zinc ion binding
GO:0001525 IEA:UniProtKB-KW P angiogenesis
GO:0007155 IEA:UniProtKB-KW P cell adhesion
GO:0006874 IMP:MGI P cellular calcium ion homeostasis
GO:0071322 IDA:MGI P cellular response to carbohydrate stimulus
GO:0002062 IDA:MGI P chondrocyte differentiation
GO:0000188 IMP:MGI P inactivation of MAPK activity
GO:0050930 IMP:MGI P induction of positive chemotaxis
GO:0097193 IMP:MGI P intrinsic apoptotic signaling pathway
GO:0008285 IGI:MGI P negative regulation of cell proliferation
GO:0034351 ISS:UniProtKB P negative regulation of glial cell apoptotic process
GO:0046325 IMP:MGI P negative regulation of glucose import
GO:0046627 IMP:MGI P negative regulation of insulin receptor signaling pathway
GO:0006469 IMP:MGI P negative regulation of protein kinase activity
GO:0001933 IMP:MGI P negative regulation of protein phosphorylation
GO:0030593 IMP:MGI P neutrophil chemotaxis
GO:0036289 IDA:MGI P peptidyl-serine autophosphorylation
GO:0070374 ISS:UniProtKB P positive regulation of ERK1 and ERK2 cascade
GO:0045766 ISS:UniProtKB P positive regulation of angiogenesis
GO:0010613 ISS:UniProtKB P positive regulation of cardiac muscle hypertrophy
GO:0045785 ISS:UniProtKB P positive regulation of cell adhesion
GO:0030335 ISS:UniProtKB P positive regulation of cell migration
GO:2000707 IMP:UniProtKB P positive regulation of dense core granule biogenesis
GO:0010595 ISS:UniProtKB P positive regulation of endothelial cell migration
GO:0001938 ISS:UniProtKB P positive regulation of endothelial cell proliferation
GO:0050729 IMP:MGI P positive regulation of inflammatory response
GO:0031666 ISS:UniProtKB P positive regulation of lipopolysaccharide-mediated signaling pathway
GO:0045651 IMP:UniProtKB P positive regulation of macrophage differentiation
GO:0045931 ISS:UniProtKB P positive regulation of mitotic cell cycle
GO:0001934 IMP:MGI P positive regulation of protein phosphorylation
GO:0006468 IDA:MGI P protein phosphorylation
GO:0006937 IMP:MGI P regulation of muscle contraction
GO:0050730 IMP:MGI P regulation of peptidyl-tyrosine phosphorylation
GO:0090330 IMP:UniProtKB P regulation of platelet aggregation
GO:0002026 IMP:MGI P regulation of the force of heart contraction

KEGG Pathway Links

KEGG Pathway ID Description
mmu04261 Adrenergic signaling in cardiomyocytes
mmu04750 Inflammatory mediator regulation of TRP channels
mmu04921 Oxytocin signaling pathway
mmu04919 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_MOUSE
UniProt ID
P20444
Species
Mouse

Comments

Comment Type Description
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Cofactor Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000250};
Disease Note=Expression of the mutant form UV25 causes malignant transformation of cells.
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, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades 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. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. {ECO:0000269|PubMed:19147982, ECO:0000269|PubMed:8321321, ECO:0000269|PubMed:9508782}.
Interaction O08785:Clock; NbExp=3; IntAct=EBI-6976815, EBI-79859;
Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}.
Similarity Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
Similarity Contains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}.
Similarity Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Similarity Contains 2 phorbol-ester/DAG-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00226}.
Subcellular Location Cytoplasm. Cell membrane; Peripheral membrane protein. Mitochondrion membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Nucleus. Note=Translocated to the cell periphery upon tetradecanoyl phorbol acetate (TPA) treatment.
Subunit 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. {ECO:0000250, ECO:0000269|PubMed:20093473, ECO:0000269|PubMed:7844141}.

Identical and Related Proteins

Unique RefSeq proteins for LMP000331 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
164663791 RefSeq NP_035231 672 protein kinase C alpha type

Identical Sequences to LMP000331 proteins

Reference Database Accession Length Protein Name
GI:164663791 DBBJ BAE27664.1 672 unnamed protein product [Mus musculus]
GI:164663791 EMBL CAA36908.1 672 protein kinase C [Mus musculus]
GI:164663791 GenBank AAH96493.1 672 Prkca protein [Mus musculus]
GI:164663791 GenBank ABK42344.1 672 protein kinase C alpha [synthetic construct]
GI:164663791 GenBank EDL34340.1 672 protein kinase C, alpha [Mus musculus]

Related Sequences to LMP000331 proteins

Reference Database Accession Length Protein Name
GI:164663791 EMBL CAA30266.1 672 unnamed protein product [Rattus rattus]
GI:164663791 GenBank AAI69007.1 672 Prkca protein [Rattus norvegicus]
GI:164663791 RefSeq XP_004655188.1 672 PREDICTED: protein kinase C alpha type [Jaculus jaculus]
GI:164663791 RefSeq XP_005070045.1 672 PREDICTED: protein kinase C alpha type [Mesocricetus auratus]
GI:164663791 RefSeq XP_007621540.1 672 PREDICTED: protein kinase C alpha type isoform X3 [Cricetulus griseus]
GI:164663791 SwissProt P05696.3 672 RecName: Full=Protein kinase C alpha type; Short=PKC-A; Short=PKC-alpha [Rattus norvegicus]