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UniProtKB - P20444 (KPCA_MOUSE)

Protein

Protein kinase C alpha type

Gene

Prkca

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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 (By similarity). 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.By similarity3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Ca2+By similarityNote: Binds 3 Ca2+ ions per subunit. The ions are bound to the C2 domain.By similarity

Activity regulationi

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi186Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi187Calcium 1By similarity1
Metal bindingi187Calcium 2By similarity1
Metal bindingi193Calcium 2By similarity1
Binding sitei195Inositol phosphate groupBy similarity1
Binding sitei245Inositol phosphate groupBy similarity1
Metal bindingi246Calcium 1By similarity1
Metal bindingi246Calcium 2By similarity1
Metal bindingi247Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi248Calcium 1By similarity1
Metal bindingi248Calcium 2By similarity1
Metal bindingi248Calcium 3By similarity1
Metal bindingi252Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi254Calcium 1By similarity1
Metal bindingi254Calcium 3By similarity1
Binding sitei368ATPPROSITE-ProRule annotation1
Active sitei463Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri36 – 86Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri101 – 151Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi345 – 353ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processAngiogenesis, Apoptosis, Cell adhesion
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C alpha type (EC:2.7.11.13)
Short name:
PKC-A
Short name:
PKC-alpha
Gene namesi
Name:Prkca
Synonyms:Pkca
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:97595 Prkca

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Expression of the mutant form UV25 causes malignant transformation of cells.

Chemistry databases

ChEMBLiCHEMBL2567

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000556802 – 672Protein kinase C alpha typeAdd BLAST671

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei10PhosphoserineBy similarity1
Modified residuei226PhosphoserineBy similarity1
Modified residuei319PhosphoserineBy similarity1
Modified residuei494PhosphothreonineBy similarity1
Modified residuei495PhosphothreonineBy similarity1
Modified residuei497Phosphothreonine; by PDPK1By similarity1
Modified residuei501PhosphothreonineBy similarity1
Modified residuei628N6-acetyllysineBy similarity1
Modified residuei631Phosphothreonine; by autocatalysisSequence analysisBy similarity1
Modified residuei638Phosphothreonine; by autocatalysisBy similarity1
Modified residuei651PhosphoserineBy similarity1
Modified residuei657PhosphoserineBy similarity1
Modified residuei658Phosphotyrosine; by SYK1 Publication1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP20444
MaxQBiP20444
PaxDbiP20444
PeptideAtlasiP20444
PRIDEiP20444

PTM databases

iPTMnetiP20444
PhosphoSitePlusiP20444
SwissPalmiP20444

Expressioni

Gene expression databases

CleanExiMM_PRKCA

Interactioni

Subunit structurei

Interacts with ADAP1/CENTA1 and CSPG4 (By similarity). Interacts with PRKCABP (PubMed:7844141). Binds to CAVIN2 in the presence of phosphatidylserine. Interacts with PICK1 (via PDZ domain). Interacts with TRIM41 (By similarity). Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and RACK1 (PubMed:20093473). Interacts with PARD3 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ClockO087853EBI-6976815,EBI-79859

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi202194, 13 interactors
DIPiDIP-532N
IntActiP20444, 5 interactors
MINTiP20444
STRINGi10090.ENSMUSP00000062392

Chemistry databases

BindingDBiP20444

Structurei

3D structure databases

DisProtiDP01105
ProteinModelPortaliP20444
SMRiP20444
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini172 – 260C2PROSITE-ProRule annotationAdd BLAST89
Domaini339 – 597Protein kinasePROSITE-ProRule annotationAdd BLAST259
Domaini598 – 668AGC-kinase C-terminalAdd BLAST71

Sequence similaritiesi

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri36 – 86Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri101 – 151Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiP20444
KOiK02677
PhylomeDBiP20444

Family and domain databases

CDDicd00029 C1, 2 hits
cd05615 STKc_cPKC_alpha, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR034663 cPKC_alpha
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR002219 PE/DAG-bd
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR014375 Protein_kinase_C_a/b/g
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00130 C1_1, 2 hits
PF00168 C2, 1 hit
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000550 PKC_alpha, 1 hit
PRINTSiPR00360 C2DOMAIN
PR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00239 C2, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50004 C2, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS00479 ZF_DAG_PE_1, 2 hits
PS50081 ZF_DAG_PE_2, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P20444-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MADVYPANDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC 
        60         70         80         90        100
SHCTDFIWGF GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS 
       110        120        130        140        150
KHKFKIHTYG SPTFCDHCGS LLYGLIHQGM KCDTCDMNVH KQCVINDPSL 
       160        170        180        190        200
CGMDHTEKRG RIYLKAEVTD EKLHVTVRDA KNLIPMDPNG LSDPYVKLKL 
       210        220        230        240        250
IPDPKNESKQ KTKTIRSNLN PQWNESFTFK LKPSDKDRRL SVEIWDWDRT 
       260        270        280        290        300
TRNDFMGSLS FGVSELMKMP ASGWYKAHNQ EEGEYYNVPI PEGDEEGNME 
       310        320        330        340        350
LRQKFEKAKL GPVGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF 
       360        370        380        390        400
GKVMLADRKG TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALLDKPPFL 
       410        420        430        440        450
TQLHSCFQTV DRLYFVMEYV NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG 
       460        470        480        490        500
LFFLHKRGII YRDLKLNNVM LNSEGHIKIA DFGMCKEHMM DGVTTRTFCG 
       510        520        530        540        550
TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG EDEDELFQSI 
       560        570        580        590        600
MEHNVSYPKS LSKEAVSICK GLMTKQPAKR LGCGPEGERD VREHAFFRRI 
       610        620        630        640        650
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVLTPP DQLVIANIDQ 
       660        670 
SDFEGFSYVN PQFVHPILQS AV
Length:672
Mass (Da):76,852
Last modified:January 23, 2007 - v3
Checksum:i394B48C952BB6D50
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q4VA93Q4VA93_MOUSE
Protein kinase C
Prkca mCG_140727
672Annotation score:
Q3TQ39Q3TQ39_MOUSE
Non-specific serine/threonine prote...
Prkca
248Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti147D → V in CAA36908 (PubMed:2469625).Curated1
Sequence conflicti147D → V in CAA36907 (PubMed:2469625).Curated1
Sequence conflicti218N → T in CAA36908 (PubMed:2469625).Curated1
Sequence conflicti218N → T in CAA36907 (PubMed:2469625).Curated1
Sequence conflicti277 – 278AH → LL in CAA36908 (PubMed:2469625).Curated2
Sequence conflicti277 – 278AH → LL in CAA36907 (PubMed:2469625).Curated2
Sequence conflicti313V → A in CAA36908 (PubMed:2469625).Curated1
Sequence conflicti313V → A in CAA36907 (PubMed:2469625).Curated1
Sequence conflicti467N → D in CAA36908 (PubMed:2469625).Curated1
Sequence conflicti467N → D in CAA36907 (PubMed:2469625).Curated1
Sequence conflicti472N → D in CAA36908 (PubMed:2469625).Curated1
Sequence conflicti472N → D in CAA36907 (PubMed:2469625).Curated1
Sequence conflicti576Q → H in CAA36908 (PubMed:2469625).Curated1
Sequence conflicti576Q → H in CAA36907 (PubMed:2469625).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti106I → V in mutant form UV25. 1 Publication1
Natural varianti111S → G in mutant form UV25. 1 Publication1
Natural varianti240L → Q in mutant form UV25. 1 Publication1
Natural varianti339F → L in mutant form UV25. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25811 mRNA Translation: AAA39934.1
X52685 mRNA Translation: CAA36908.1
X52684 mRNA Translation: CAA36907.1
PIRiS07104 KIMSCA
RefSeqiNP_035231.2, NM_011101.3
UniGeneiMm.222178

Genome annotation databases

GeneIDi18750
KEGGimmu:18750

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25811 mRNA Translation: AAA39934.1
X52685 mRNA Translation: CAA36908.1
X52684 mRNA Translation: CAA36907.1
PIRiS07104 KIMSCA
RefSeqiNP_035231.2, NM_011101.3
UniGeneiMm.222178

3D structure databases

DisProtiDP01105
ProteinModelPortaliP20444
SMRiP20444
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202194, 13 interactors
DIPiDIP-532N
IntActiP20444, 5 interactors
MINTiP20444
STRINGi10090.ENSMUSP00000062392

Chemistry databases

BindingDBiP20444
ChEMBLiCHEMBL2567

PTM databases

iPTMnetiP20444
PhosphoSitePlusiP20444
SwissPalmiP20444

Proteomic databases

EPDiP20444
MaxQBiP20444
PaxDbiP20444
PeptideAtlasiP20444
PRIDEiP20444

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi18750
KEGGimmu:18750

Organism-specific databases

CTDi5578
MGIiMGI:97595 Prkca

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiP20444
KOiK02677
PhylomeDBiP20444

Enzyme and pathway databases

BRENDAi2.7.11.13 3474

Miscellaneous databases

ChiTaRSiPrkca mouse
PROiPR:P20444
SOURCEiSearch...

Gene expression databases

CleanExiMM_PRKCA

Family and domain databases

CDDicd00029 C1, 2 hits
cd05615 STKc_cPKC_alpha, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR034663 cPKC_alpha
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR002219 PE/DAG-bd
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR014375 Protein_kinase_C_a/b/g
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00130 C1_1, 2 hits
PF00168 C2, 1 hit
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000550 PKC_alpha, 1 hit
PRINTSiPR00360 C2DOMAIN
PR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00239 C2, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50004 C2, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS00479 ZF_DAG_PE_1, 2 hits
PS50081 ZF_DAG_PE_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiKPCA_MOUSE
AccessioniPrimary (citable) accession number: P20444
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 195 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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