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Protein

Protein kinase C epsilon type

Gene

Prkce

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

Functioni

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 AKT1.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei437ATPPROSITE-ProRule annotation1
Active sitei532Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri169 – 220Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri242 – 292Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi414 – 422ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell adhesion, Cell cycle, Cell division, Immunity
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13 3474
ReactomeiR-MMU-114508 Effects of PIP2 hydrolysis
R-MMU-1250196 SHC1 events in ERBB2 signaling
R-MMU-1489509 DAG and IP3 signaling
R-MMU-2029485 Role of phospholipids in phagocytosis

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C epsilon type (EC:2.7.11.13)
Alternative name(s):
nPKC-epsilon
Gene namesi
Name:Prkce
Synonyms:Pkce, Pkcea
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:97599 Prkce

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, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi346S → A: Loss of interaction with YWHAB and defects in the completion of cytokinesis. 1 Publication1
Mutagenesisi368S → A: Loss of interaction with YWHAB and defects in the completion of cytokinesis. 1 Publication1
Mutagenesisi729S → A, E or T: Loss of localization to the perinuclear region. Loss of translocation to the nucleus upon PMA stimulation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4366
GuidetoPHARMACOLOGYi1486

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000556981 – 737Protein kinase C epsilon typeAdd BLAST737

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62PhosphoserineCombined sources1
Modified residuei228PhosphothreonineBy similarity1
Modified residuei234Phosphoserine1 Publication1
Modified residuei309PhosphothreonineBy similarity1
Modified residuei316Phosphoserine1 Publication1
Modified residuei329PhosphoserineCombined sources1
Modified residuei337PhosphoserineCombined sources1
Modified residuei346Phosphoserine; by GSK3-betaCombined sources1 Publication1
Modified residuei349PhosphothreonineCombined sources1
Modified residuei350Phosphoserine; by MAPK11 and MAPK141 Publication1
Modified residuei368Phosphoserine; by autocatalysis2 Publications1
Modified residuei388PhosphoserineCombined sources1
Modified residuei566Phosphothreonine; by PDPK1By similarity1
Modified residuei703Phosphothreonine; by autocatalysisSequence analysis1
Modified residuei710PhosphothreonineCombined sources1
Modified residuei729Phosphoserine; by autocatalysis1 Publication1

Post-translational modificationi

Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729 (By similarity). Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB.By similarity3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP16054
PaxDbiP16054
PeptideAtlasiP16054
PRIDEiP16054

PTM databases

iPTMnetiP16054
PhosphoSitePlusiP16054
SwissPalmiP16054

Expressioni

Gene expression databases

BgeeiENSMUSG00000045038 Expressed in 280 organ(s), highest expression level in dentate gyrus of hippocampal formation
CleanExiMM_PRKCE
ExpressionAtlasiP16054 baseline and differential
GenevisibleiP16054 MM

Interactioni

Subunit structurei

Forms a ternary complex with TRIM63 and GN2BL1. Can form a complex with PDLIM5 and N-type calcium channel. Interacts with COPB1, DGKQ and STAT3 (By similarity). Interacts with YWHAB. Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (By similarity).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202198, 12 interactors
DIPiDIP-31066N
IntActiP16054, 97 interactors
MINTiP16054
STRINGi10090.ENSMUSP00000094873

Chemistry databases

BindingDBiP16054

Structurei

3D structure databases

ProteinModelPortaliP16054
SMRiP16054
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 99C2PROSITE-ProRule annotationAdd BLAST99
Domaini408 – 668Protein kinasePROSITE-ProRule annotationAdd BLAST261
Domaini669 – 737AGC-kinase C-terminalAdd BLAST69

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi223 – 228Interaction with actin6

Domaini

The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri169 – 220Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri242 – 292Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00930000150815
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiP16054
KOiK18050
OMAiPCDQELK
OrthoDBiEOG091G0QRS
PhylomeDBiP16054
TreeFamiTF351133

Family and domain databases

CDDicd00029 C1, 2 hits
cd05591 STKc_nPKC_epsilon, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR034669 nPKC_epsilon
IPR002219 PE/DAG-bd
IPR027274 PKC_epsilon
IPR017892 Pkinase_C
IPR014376 Prot_kin_PKC_delta
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
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
PIRSFiPIRSF000551 PKC_delta, 1 hit
PIRSF501106 Protein_kin_C_epsilon, 1 hit
PRINTSiPR00008 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.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P16054-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVVFNGLLKI KICEAVSLKP TAWSLRHAVG PRPQTFLLDP YIALNVDDSR
60 70 80 90 100
IGQTATKQKT NSPAWHDEFV TDVCNGRKIE LAVFHDAPIG YDDFVANCTI
110 120 130 140 150
QFEELLQNGS RHFEDWIDLE PEGKVYVIID LSGSSGEAPK DNEERVFRER
160 170 180 190 200
MRPRKRQGAV RRRVHQVNGH KFMATYLRQP TYCSHCRDFI WGVIGKQGYQ
210 220 230 240 250
CQVCTCVVHK RCHELIITKC AGLKKQETPD EVGSQRFSVN MPHKFGIHNY
260 270 280 290 300
KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA
310 320 330 340 350
KVLADLGVTP DKITNSGQRR KKLAAGAESP QPASGNSPSE DDRSKSAPTS
360 370 380 390 400
PCDQELKELE NNIRKALSFD NRGEEHRASS ATDGQLASPG ENGEVRPGQA
410 420 430 440 450
KRLGLDEFNF IKVLGKGSFG KVMLAELKGK DEVYAVKVLK KDVILQDDDV
460 470 480 490 500
DCTMTEKRIL ALARKHPYLT QLYCCFQTKD RLFFVMEYVN GGDLMFQIQR
510 520 530 540 550
SRKFDEPRSR FYAAEVTSAL MFLHQHGVIY RDLKLDNILL DAEGHCKLAD
560 570 580 590 600
FGMCKEGIMN GVTTTTFCGT PDYIAPEILQ ELEYGPSVDW WALGVLMYEM
610 620 630 640 650
MAGQPPFEAD NEDDLFESIL HDDVLYPVWL SKEAVSILKA FMTKNPHKRL
660 670 680 690 700
GCVAAQNGED AIKQHPFFKE IDWVLLEQKK IKPPFKPRIK TKRDVNNFDQ
710 720 730
DFTREEPILT LVDEAIIKQI NQEEFKGFSY FGEDLMP
Length:737
Mass (Da):83,561
Last modified:April 1, 1990 - v1
Checksum:i7AEBB8CC10C99F57
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8C944Q8C944_MOUSE
Protein kinase C epsilon type
Prkce
125Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028009 mRNA Translation: AAB84189.1
AF325507 mRNA Translation: AAG53692.1
CCDSiCCDS29008.1
PIRiS02270 KIMSCE
RefSeqiNP_035234.1, NM_011104.3
UniGeneiMm.24614

Genome annotation databases

EnsembliENSMUST00000097274; ENSMUSP00000094873; ENSMUSG00000045038
ENSMUST00000097275; ENSMUSP00000094874; ENSMUSG00000045038
GeneIDi18754
KEGGimmu:18754
UCSCiuc008dug.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028009 mRNA Translation: AAB84189.1
AF325507 mRNA Translation: AAG53692.1
CCDSiCCDS29008.1
PIRiS02270 KIMSCE
RefSeqiNP_035234.1, NM_011104.3
UniGeneiMm.24614

3D structure databases

ProteinModelPortaliP16054
SMRiP16054
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202198, 12 interactors
DIPiDIP-31066N
IntActiP16054, 97 interactors
MINTiP16054
STRINGi10090.ENSMUSP00000094873

Chemistry databases

BindingDBiP16054
ChEMBLiCHEMBL4366
GuidetoPHARMACOLOGYi1486

PTM databases

iPTMnetiP16054
PhosphoSitePlusiP16054
SwissPalmiP16054

Proteomic databases

MaxQBiP16054
PaxDbiP16054
PeptideAtlasiP16054
PRIDEiP16054

Protocols and materials databases

DNASUi18754
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000097274; ENSMUSP00000094873; ENSMUSG00000045038
ENSMUST00000097275; ENSMUSP00000094874; ENSMUSG00000045038
GeneIDi18754
KEGGimmu:18754
UCSCiuc008dug.2 mouse

Organism-specific databases

CTDi5581
MGIiMGI:97599 Prkce

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00930000150815
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiP16054
KOiK18050
OMAiPCDQELK
OrthoDBiEOG091G0QRS
PhylomeDBiP16054
TreeFamiTF351133

Enzyme and pathway databases

BRENDAi2.7.11.13 3474
ReactomeiR-MMU-114508 Effects of PIP2 hydrolysis
R-MMU-1250196 SHC1 events in ERBB2 signaling
R-MMU-1489509 DAG and IP3 signaling
R-MMU-2029485 Role of phospholipids in phagocytosis

Miscellaneous databases

ChiTaRSiPrkce mouse
PROiPR:P16054
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000045038 Expressed in 280 organ(s), highest expression level in dentate gyrus of hippocampal formation
CleanExiMM_PRKCE
ExpressionAtlasiP16054 baseline and differential
GenevisibleiP16054 MM

Family and domain databases

CDDicd00029 C1, 2 hits
cd05591 STKc_nPKC_epsilon, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR034669 nPKC_epsilon
IPR002219 PE/DAG-bd
IPR027274 PKC_epsilon
IPR017892 Pkinase_C
IPR014376 Prot_kin_PKC_delta
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
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
PIRSFiPIRSF000551 PKC_delta, 1 hit
PIRSF501106 Protein_kin_C_epsilon, 1 hit
PRINTSiPR00008 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 nameiKPCE_MOUSE
AccessioniPrimary (citable) accession number: P16054
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 7, 2018
This is version 193 of the entry and version 1 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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