PRKCA (protein kinase C alpha)

Gene

• Entrez ID: 5578
• Gene name: Protein kinase C alpha
• Gene symbol: PRKCA
• Synonyms: AAG6, PKC-alpha, PKCA, PKCI+/-, PKCalpha, PRKACA
• Chromosome: 17
• Chromosome location: 17q24.2
• 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs16960228	G>A	Drug-response	Intron variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020045	hsa-miR-375	Microarray	20215506
MIRT040995	hsa-miR-505-3p	CLASH	23622248
MIRT041382	hsa-miR-193b-3p	CLASH	23622248
MIRT049636	hsa-miR-92a-3p	CLASH	23622248
MIRT050756	hsa-miR-17-3p	CLASH	23622248
MIRT053072	hsa-miR-203a-3p	qRT-PCR	24040137
MIRT439901	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT614829	hsa-miR-371b-5p	HITS-CLIP	23824327
MIRT614829	hsa-miR-371b-5p	HITS-CLIP	19536157
MIRT614829	hsa-miR-371b-5p	HITS-CLIP	28735896
MIRT614830	hsa-miR-6828-5p	HITS-CLIP	23824327
MIRT614830	hsa-miR-6828-5p	HITS-CLIP	19536157
MIRT614830	hsa-miR-6828-5p	HITS-CLIP	28735896
MIRT614831	hsa-miR-1976	HITS-CLIP	23824327
MIRT614831	hsa-miR-1976	HITS-CLIP	19536157
MIRT614831	hsa-miR-1976	HITS-CLIP	28735896
MIRT614832	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT614832	hsa-miR-6747-3p	HITS-CLIP	19536157
MIRT614832	hsa-miR-6747-3p	HITS-CLIP	28735896
MIRT614833	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT614833	hsa-miR-6727-3p	HITS-CLIP	19536157
MIRT614833	hsa-miR-6727-3p	HITS-CLIP	28735896
MIRT614834	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT614834	hsa-miR-4722-3p	HITS-CLIP	19536157
MIRT614834	hsa-miR-4722-3p	HITS-CLIP	28735896
MIRT614835	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT614835	hsa-miR-660-3p	HITS-CLIP	28735896
MIRT614836	hsa-miR-5193	HITS-CLIP	23824327
MIRT614836	hsa-miR-5193	HITS-CLIP	19536157
MIRT614836	hsa-miR-5193	HITS-CLIP	28735896
MIRT614837	hsa-miR-5196-3p	HITS-CLIP	23824327
MIRT614837	hsa-miR-5196-3p	HITS-CLIP	19536157
MIRT614837	hsa-miR-5196-3p	HITS-CLIP	28735896
MIRT700595	hsa-miR-6821-5p	HITS-CLIP	23313552
MIRT700596	hsa-miR-6842-3p	HITS-CLIP	23313552
MIRT700597	hsa-miR-647	HITS-CLIP	23313552
MIRT700598	hsa-miR-6514-3p	HITS-CLIP	23313552
MIRT700599	hsa-miR-7977	HITS-CLIP	23313552
MIRT700600	hsa-miR-1268b	HITS-CLIP	23313552
MIRT700601	hsa-miR-1268a	HITS-CLIP	23313552
MIRT700602	hsa-miR-585-3p	HITS-CLIP	23313552
MIRT700603	hsa-miR-5787	HITS-CLIP	23313552
MIRT700604	hsa-miR-4505	HITS-CLIP	23313552
MIRT700605	hsa-miR-4430	HITS-CLIP	23313552
MIRT700606	hsa-miR-3652	HITS-CLIP	23313552
MIRT700607	hsa-miR-24-3p	HITS-CLIP	23313552
MIRT700608	hsa-miR-4284	HITS-CLIP	23313552
MIRT700609	hsa-miR-6847-3p	HITS-CLIP	23313552
MIRT700610	hsa-miR-6811-3p	HITS-CLIP	23313552
MIRT700611	hsa-miR-214-5p	HITS-CLIP	23313552
MIRT700612	hsa-miR-4486	HITS-CLIP	23313552
MIRT733898	hsa-miR-142-3p	Microarray, qRT-PCR, Western blot	27113904
MIRT734463	hsa-miR-150-5p	Luciferase reporter assay, qRT-PCR, Western blot	26232986

Transcription factors

Transcription factor	Regulation	Reference
RARA	Activation	11525643
TFAP2A	Activation	12269829

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEA
GO:0001938	Process	Positive regulation of endothelial cell proliferation	IMP	11909826
GO:0002159	Process	Desmosome assembly	IMP	18474624
GO:0004672	Function	Protein kinase activity	IDA	10770950
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	7520444, 7539802, 12391145, 17392515
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0004697	Function	Protein kinase C activity	ISS
GO:0004698	Function	Calcium-dependent protein kinase C activity	IEA
GO:0005178	Function	Integrin binding	ISS
GO:0005515	Function	Protein binding	IPI	12571249, 12893243, 16810323, 17244820, 18566587, 21703451, 21952047, 24658140, 30017192, 31980649, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	15632189, 23990668
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005783	Component	Endoplasmic reticulum	IDA	18556656
GO:0005829	Component	Cytosol	IDA	17983652
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	15632189, 23990668
GO:0005886	Component	Plasma membrane	TAS
GO:0006468	Process	Protein phosphorylation	IDA	10770950
GO:0007077	Process	Mitotic nuclear envelope disassembly	TAS
GO:0007155	Process	Cell adhesion	IEA
GO:0007411	Process	Axon guidance	TAS
GO:0008270	Function	Zinc ion binding	IEA
GO:0010595	Process	Positive regulation of endothelial cell migration	IMP	11909826
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	ISS
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	TAS	26078884
GO:0018107	Process	Peptidyl-threonine phosphorylation	ISS	16717194
GO:0019899	Function	Enzyme binding	IDA	18556656
GO:0030168	Process	Platelet activation	TAS
GO:0030335	Process	Positive regulation of cell migration	IMP	23990668
GO:0031666	Process	Positive regulation of lipopolysaccharide-mediated signaling pathway	IMP	9830023
GO:0031966	Component	Mitochondrial membrane	IEA
GO:0034351	Process	Negative regulation of glial cell apoptotic process	IMP	9927633
GO:0035403	Function	Histone kinase activity (H3-T6 specific)	IDA	20228790
GO:0035408	Process	Histone H3-T6 phosphorylation	IDA	20228790
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035866	Component	Alphav-beta3 integrin-PKCalpha complex	ISS
GO:0038128	Process	ERBB2 signaling pathway	TAS
GO:0043488	Process	Regulation of mRNA stability	TAS
GO:0043536	Process	Positive regulation of blood vessel endothelial cell migration	IDA	20011604
GO:0045651	Process	Positive regulation of macrophage differentiation	ISS
GO:0045766	Process	Positive regulation of angiogenesis	IMP	11909826
GO:0045780	Process	Positive regulation of bone resorption	ISS
GO:0045785	Process	Positive regulation of cell adhesion	IMP	11909826
GO:0045931	Process	Positive regulation of mitotic cell cycle	IMP	10848585
GO:0048471	Component	Perinuclear region of cytoplasm	ISS
GO:0050796	Process	Regulation of insulin secretion	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	ISS
GO:0070555	Process	Response to interleukin-1	IMP	19281832
GO:0090330	Process	Regulation of platelet aggregation	IDA	12724315
GO:0097190	Process	Apoptotic signaling pathway	TAS	10825394
GO:0106071	Process	Positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISS
GO:2000707	Process	Positive regulation of dense core granule biogenesis	ISS

Other IDs

• MIM: 176960
• HGNC: 9393
• e!Ensembl: ENSG00000154229

Protein

• UniProt ID: P17252
• Protein name: Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13)
• Protein 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. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). 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. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteosomal degradation (By similarity).
• PDB: 2ELI, 3IW4, 4DNL, 4RA4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00130	C1_1	37 → 89	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00130	C1_1	102 → 154	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00168	C2	171 → 277	C2 domain	Domain
  PF00069	Pkinase	339 → 597	Protein kinase domain	Domain
  PF00433	Pkinase_C	623 → 658	Protein kinase C terminal domain	Family

• Sequence:

  MADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGF
  GKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGS
  LLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDA
  KNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRL
  SVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNME
  LRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKG
  TEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYV
  NGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIA
  DFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDG
  EDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFFRRI
  DWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVN
  PQFVHPILQSAV

• Sequence length: 672