CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004407
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C epsilon type 
Protein Synonyms/Alias
 nPKC-epsilon 
Gene Name
 Prkce 
Gene Synonyms/Alias
 Pkce; Pkcea 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
312DLGVTPDKITNSGQRubiquitination[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-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL- mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. 
Sequence Annotation
 DOMAIN 1 99 C2.
 DOMAIN 408 668 Protein kinase.
 DOMAIN 669 737 AGC-kinase C-terminal.
 ZN_FING 169 220 Phorbol-ester/DAG-type 1.
 ZN_FING 242 292 Phorbol-ester/DAG-type 2.
 NP_BIND 414 422 ATP (By similarity).
 MOTIF 223 228 Interaction with actin.
 ACT_SITE 532 532 Proton acceptor (By similarity).
 BINDING 437 437 ATP (By similarity).
 MOD_RES 228 228 Phosphothreonine (By similarity).
 MOD_RES 234 234 Phosphoserine.
 MOD_RES 309 309 Phosphothreonine (By similarity).
 MOD_RES 316 316 Phosphoserine.
 MOD_RES 329 329 Phosphoserine (By similarity).
 MOD_RES 337 337 Phosphoserine.
 MOD_RES 346 346 Phosphoserine; by GSK3-beta.
 MOD_RES 349 349 Phosphothreonine.
 MOD_RES 350 350 Phosphoserine; by MAPK11 and MAPK14.
 MOD_RES 368 368 Phosphoserine; by autocatalysis.
 MOD_RES 388 388 Phosphoserine (By similarity).
 MOD_RES 566 566 Phosphothreonine; by PDPK1 (By
 MOD_RES 703 703 Phosphothreonine; by autocatalysis
 MOD_RES 710 710 Phosphothreonine; by autocatalysis
 MOD_RES 729 729 Phosphoserine; by autocatalysis  
Keyword
 ATP-binding; Cell adhesion; Cell cycle; Cell division; Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; Immunity; Kinase; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 737 AA 
Protein Sequence
MVVFNGLLKI KICEAVSLKP TAWSLRHAVG PRPQTFLLDP YIALNVDDSR IGQTATKQKT 60
NSPAWHDEFV TDVCNGRKIE LAVFHDAPIG YDDFVANCTI QFEELLQNGS RHFEDWIDLE 120
PEGKVYVIID LSGSSGEAPK DNEERVFRER MRPRKRQGAV RRRVHQVNGH KFMATYLRQP 180
TYCSHCRDFI WGVIGKQGYQ CQVCTCVVHK RCHELIITKC AGLKKQETPD EVGSQRFSVN 240
MPHKFGIHNY KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA 300
KVLADLGVTP DKITNSGQRR KKLAAGAESP QPASGNSPSE DDRSKSAPTS PCDQELKELE 360
NNIRKALSFD NRGEEHRASS ATDGQLASPG ENGEVRPGQA KRLGLDEFNF IKVLGKGSFG 420
KVMLAELKGK DEVYAVKVLK KDVILQDDDV DCTMTEKRIL ALARKHPYLT QLYCCFQTKD 480
RLFFVMEYVN GGDLMFQIQR SRKFDEPRSR FYAAEVTSAL MFLHQHGVIY RDLKLDNILL 540
DAEGHCKLAD FGMCKEGIMN GVTTTTFCGT PDYIAPEILQ ELEYGPSVDW WALGVLMYEM 600
MAGQPPFEAD NEDDLFESIL HDDVLYPVWL SKEAVSILKA FMTKNPHKRL GCVAAQNGED 660
AIKQHPFFKE IDWVLLEQKK IKPPFKPRIK TKRDVNNFDQ DFTREEPILT LVDEAIIKQI 720
NQEEFKGFSY FGEDLMP 737 
Gene Ontology
 GO:0071944; C:cell periphery; IDA:UniProtKB.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; IDA:MGI.
 GO:0005783; C:endoplasmic reticulum; IEA:Compara.
 GO:0016020; C:membrane; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; IDA:MGI.
 GO:0005634; C:nucleus; IDA:MGI.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0003785; F:actin monomer binding; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004699; F:calcium-independent protein kinase C activity; IDA:MGI.
 GO:0008047; F:enzyme activator activity; IEA:Compara.
 GO:0035276; F:ethanol binding; IDA:MGI.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0030546; F:receptor activator activity; IDA:MGI.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0071361; P:cellular response to ethanol; IGI:MGI.
 GO:0071456; P:cellular response to hypoxia; IDA:MGI.
 GO:0007635; P:chemosensory behavior; TAS:MGI.
 GO:0035556; P:intracellular signal transduction; IEA:InterPro.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB.
 GO:0035641; P:locomotory exploration behavior; IGI:MGI.
 GO:0002281; P:macrophage activation involved in immune response; IMP:MGI.
 GO:0030838; P:positive regulation of actin filament polymerization; IDA:UniProtKB.
 GO:0043085; P:positive regulation of catalytic activity; IEA:GOC.
 GO:0010811; P:positive regulation of cell-substrate adhesion; IMP:MGI.
 GO:2001031; P:positive regulation of cellular glucuronidation; IEA:Compara.
 GO:0032467; P:positive regulation of cytokinesis; ISS:UniProtKB.
 GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
 GO:0010763; P:positive regulation of fibroblast migration; IMP:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:MGI.
 GO:0032024; P:positive regulation of insulin secretion; IMP:MGI.
 GO:0050996; P:positive regulation of lipid catabolic process; IMP:MGI.
 GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
 GO:0070257; P:positive regulation of mucus secretion; IMP:MGI.
 GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IMP:MGI.
 GO:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
 GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
 GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
 GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:MGI.
 GO:0043278; P:response to morphine; IMP:MGI.
 GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; IMP:UniProtKB. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR018029; C2_membr_targeting.
 IPR020454; DAG/PE-bd.
 IPR011009; Kinase-like_dom.
 IPR027274; PKC_epsilon.
 IPR017892; Pkinase_C.
 IPR014376; Prot_kin_PKC_delta.
 IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 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
 PR00008; DAGPEDOMAIN.