CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004870
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C alpha type 
Protein Synonyms/Alias
 PKC-A; PKC-alpha 
Gene Name
 Prkca 
Gene Synonyms/Alias
 Pkca 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
197GLSDPYVKLKLIPDPubiquitination[1]
199SDPYVKLKLIPDPKNubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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 cascade 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. 
Sequence Annotation
 DOMAIN 172 260 C2.
 DOMAIN 339 597 Protein kinase.
 DOMAIN 598 668 AGC-kinase C-terminal.
 ZN_FING 36 86 Phorbol-ester/DAG-type 1.
 ZN_FING 101 151 Phorbol-ester/DAG-type 2.
 NP_BIND 345 353 ATP (By similarity).
 ACT_SITE 463 463 Proton acceptor (By similarity).
 METAL 186 186 Calcium 1; via carbonyl oxygen (By
 METAL 187 187 Calcium 1 (By similarity).
 METAL 187 187 Calcium 2 (By similarity).
 METAL 193 193 Calcium 2 (By similarity).
 METAL 246 246 Calcium 1 (By similarity).
 METAL 246 246 Calcium 2 (By similarity).
 METAL 247 247 Calcium 2; via carbonyl oxygen (By
 METAL 248 248 Calcium 1 (By similarity).
 METAL 248 248 Calcium 2 (By similarity).
 METAL 248 248 Calcium 3 (By similarity).
 METAL 252 252 Calcium 3; via carbonyl oxygen (By
 METAL 254 254 Calcium 1 (By similarity).
 METAL 254 254 Calcium 3 (By similarity).
 BINDING 195 195 Inositol phosphate group (By similarity).
 BINDING 245 245 Inositol phosphate group (By similarity).
 BINDING 368 368 ATP (By similarity).
 MOD_RES 2 2 N-acetylalanine (By similarity).
 MOD_RES 226 226 Phosphoserine (By similarity).
 MOD_RES 250 250 Phosphothreonine; by autocatalysis (By
 MOD_RES 319 319 Phosphoserine.
 MOD_RES 497 497 Phosphothreonine; by PDPK1 (By
 MOD_RES 628 628 N6-acetyllysine (By similarity).
 MOD_RES 631 631 Phosphothreonine; by autocatalysis
 MOD_RES 638 638 Phosphothreonine; by autocatalysis (By
 MOD_RES 651 651 Phosphoserine (By similarity).
 MOD_RES 657 657 Phosphoserine (By similarity).
 MOD_RES 658 658 Phosphotyrosine; by SYK.  
Keyword
 Acetylation; Angiogenesis; Apoptosis; ATP-binding; Calcium; Cell adhesion; Cell membrane; Complete proteome; Cytoplasm; Kinase; Membrane; Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 672 AA 
Protein Sequence
MADVYPANDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC SHCTDFIWGF 60
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS KHKFKIHTYG SPTFCDHCGS 120
LLYGLIHQGM KCDTCDMNVH KQCVINDPSL CGMDHTEKRG RIYLKAEVTD EKLHVTVRDA 180
KNLIPMDPNG LSDPYVKLKL IPDPKNESKQ KTKTIRSNLN PQWNESFTFK LKPSDKDRRL 240
SVEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKAHNQ EEGEYYNVPI PEGDEEGNME 300
LRQKFEKAKL GPVGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF GKVMLADRKG 360
TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALLDKPPFL TQLHSCFQTV DRLYFVMEYV 420
NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG LFFLHKRGII YRDLKLNNVM LNSEGHIKIA 480
DFGMCKEHMM DGVTTRTFCG TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG 540
EDEDELFQSI MEHNVSYPKS LSKEAVSICK GLMTKQPAKR LGCGPEGERD VREHAFFRRI 600
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVLTPP DQLVIANIDQ SDFEGFSYVN 660
PQFVHPILQS AV 672 
Gene Ontology
 GO:0030425; C:dendrite; IDA:MGI.
 GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IDA:MGI.
 GO:0043025; C:neuronal cell body; IDA:MGI.
 GO:0005634; C:nucleus; IDA:MGI.
 GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
 GO:0001750; C:photoreceptor outer segment; IDA:MGI.
 GO:0005886; C:plasma membrane; IDA:MGI.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004698; F:calcium-dependent protein kinase C activity; IDA:MGI.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
 GO:0071322; P:cellular response to carbohydrate stimulus; IDA:MGI.
 GO:0002062; P:chondrocyte differentiation; IDA:MGI.
 GO:0000188; P:inactivation of MAPK activity; IMP:MGI.
 GO:0050930; P:induction of positive chemotaxis; IMP:MGI.
 GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:MGI.
 GO:0008285; P:negative regulation of cell proliferation; IGI:MGI.
 GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
 GO:0046325; P:negative regulation of glucose import; IMP:MGI.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:MGI.
 GO:0030593; P:neutrophil chemotaxis; IMP:MGI.
 GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
 GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
 GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
 GO:2000707; P:positive regulation of dense core granule biogenesis; IMP:UniProtKB.
 GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
 GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0050729; P:positive regulation of inflammatory response; IMP:MGI.
 GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
 GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB.
 GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
 GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
 GO:0006937; P:regulation of muscle contraction; IMP:MGI.
 GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
 GO:0090330; P:regulation of platelet aggregation; IMP:UniProtKB.
 GO:0002026; P:regulation of the force of heart contraction; IMP:MGI. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR020477; C2_dom.
 IPR018029; C2_membr_targeting.
 IPR020454; DAG/PE-bd.
 IPR011009; Kinase-like_dom.
 IPR017892; Pkinase_C.
 IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR014375; Protein_kinase_C_a/b/g.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00130; C1_1
 PF00168; C2
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00109; C1
 SM00239; C2
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS50004; C2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS
 PR00360; C2DOMAIN.
 PR00008; DAGPEDOMAIN.