P17252 · KPCA_HUMAN
- ProteinProtein kinase C alpha type
- GenePRKCA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids672 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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. 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 proteasomal degradation (By similarity).
Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067).
Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231).
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 proteasomal degradation (By similarity).
Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067).
Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Note: Binds 3 Ca2+ ions per subunit. The ions are bound to the C2 domain.
Activity 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.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 186 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 187 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 187 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 193 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 195 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 245 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 246 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 246 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 247 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 248 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 248 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 248 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 252 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 254 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 254 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 345-353 | ATP (UniProtKB | ChEBI) | ||||
Sequence: LGKGSFGKV | ||||||
Binding site | 368 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Active site | 463 | Proton acceptor | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein kinase C alpha type
- EC number
- Short namesPKC-A; PKC-alpha
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP17252
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Mitochondrion membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_042301 | 98 | in a colorectal adenocarcinoma sample; somatic mutation | |||
Sequence: P → S | ||||||
Natural variant | VAR_042302 | 467 | in a glioblastoma multiforme sample; somatic mutation | |||
Sequence: D → N | ||||||
Natural variant | VAR_042303 | 489 | in dbSNP:rs34406842 | |||
Sequence: M → V | ||||||
Natural variant | VAR_050558 | 568 | in dbSNP:rs6504459 | |||
Sequence: V → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 542 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000055679 | 2-672 | UniProt | Protein kinase C alpha type | |||
Sequence: ADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNMELRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV | |||||||
Modified residue | 10 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 10 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 11 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 13 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 48 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 120 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 149 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 226 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 226 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 228 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 241 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 319 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 319 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 494 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 495 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 497 | UniProt | Phosphothreonine; by PDPK1 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 497 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 501 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 501 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 512 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 628 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 631 | UniProt | Phosphothreonine; by autocatalysis | ||||
Sequence: T | |||||||
Modified residue | 638 | UniProt | Phosphothreonine; by autocatalysis | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 638 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 651 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 657 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 657 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 658 | UniProt | Phosphotyrosine; by SYK | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 658 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and RACK1 (By similarity).
Interacts with ADAP1/CENTA1 (PubMed:12893243).
Interacts with CSPG4 (PubMed:15504744).
Binds to CAVIN2 in the presence of phosphatidylserine (By similarity).
Interacts with PRKCABP/PICK1 (via PDZ domain) (PubMed:15247289).
Interacts with TRIM41 (PubMed:17893151).
Interacts with PARD3 (PubMed:27925688).
Interacts with SOCS2 (By similarity).
Interacts with ADAP1/CENTA1 (PubMed:12893243).
Interacts with CSPG4 (PubMed:15504744).
Binds to CAVIN2 in the presence of phosphatidylserine (By similarity).
Interacts with PRKCABP/PICK1 (via PDZ domain) (PubMed:15247289).
Interacts with TRIM41 (PubMed:17893151).
Interacts with PARD3 (PubMed:27925688).
Interacts with SOCS2 (By similarity).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for zinc finger, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 36-86 | Phorbol-ester/DAG-type 1 | ||||
Sequence: DHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSC | ||||||
Zinc finger | 101-151 | Phorbol-ester/DAG-type 2 | ||||
Sequence: KHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLC | ||||||
Domain | 158-275 | C2 | ||||
Sequence: KRGRIYLKAEVADEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRLSVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWY | ||||||
Domain | 339-597 | Protein kinase | ||||
Sequence: FNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFF | ||||||
Domain | 598-668 | AGC-kinase C-terminal | ||||
Sequence: RRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPIL |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length672
- Mass (Da)76,750
- Last updated2011-01-11 v4
- Checksum9EB157789A062349
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 50 | in Ref. 6; AAA60098 | ||||
Sequence: C → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X52479 EMBL· GenBank· DDBJ | CAA36718.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451258 EMBL· GenBank· DDBJ | BAG70072.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451383 EMBL· GenBank· DDBJ | BAG70197.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005918 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC005988 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC006263 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC006947 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC009452 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC060796 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471099 EMBL· GenBank· DDBJ | EAW89014.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC109273 EMBL· GenBank· DDBJ | AAI09274.1 EMBL· GenBank· DDBJ | mRNA | ||
BC109274 EMBL· GenBank· DDBJ | AAI09275.1 EMBL· GenBank· DDBJ | mRNA | ||
M22199 EMBL· GenBank· DDBJ | AAA60098.1 EMBL· GenBank· DDBJ | mRNA | ||
AF395829 EMBL· GenBank· DDBJ | AAK84184.1 EMBL· GenBank· DDBJ | Genomic DNA |