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Protein

Protein kinase C epsilon type

Gene

PRKCE

Organism
Homo sapiens (Human)
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. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. 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). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. 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.

Enzyme 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

  • 14-3-3 protein binding Source: Ensembl
  • actin monomer binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • calcium-independent protein kinase C activity Source: Ensembl
  • enzyme activator activity Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • ethanol binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • protein kinase C activity Source: BHF-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
  • receptor activator activity Source: Ensembl
  • signal transducer activity Source: ProtInc

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 2681
ReactomeiR-HSA-114508 Effects of PIP2 hydrolysis
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1489509 DAG and IP3 signaling
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-418597 G alpha (z) signalling events
SABIO-RKiQ02156
SignaLinkiQ02156
SIGNORiQ02156

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000171132.13
HGNCiHGNC:9401 PRKCE
MIMi176975 gene
neXtProtiNX_Q02156

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
Mutagenesisi437K → W: Abolishes activity and S-729 phosphorylation. 1 Publication1
Mutagenesisi566T → A: Abolishes phosphorylation by PDK1, and S-729 phosphorylation. 1 Publication1
Mutagenesisi566T → E: No effect on S-729 phosphorylation. 1 Publication1
Mutagenesisi710T → E: No effect on activity; no effect on S-729 phosphorylation. 1 Publication1
Mutagenesisi729S → A: Enhances T-566 dephosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi5581
OpenTargetsiENSG00000171132
PharmGKBiPA33765

Chemistry databases

ChEMBLiCHEMBL3582
DrugBankiDB06064 KAI-1455
DB00675 Tamoxifen
GuidetoPHARMACOLOGYi1486

Polymorphism and mutation databases

BioMutaiPRKCE
DMDMi400135

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000556971 – 737Protein kinase C epsilon typeAdd BLAST737

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62PhosphoserineBy similarity1
Modified residuei228PhosphothreonineCombined sources1
Modified residuei234PhosphoserineBy similarity1
Modified residuei309PhosphothreonineCombined sources1
Modified residuei316PhosphoserineCombined sources1
Modified residuei329PhosphoserineCombined sources1
Modified residuei337PhosphoserineBy similarity1
Modified residuei346Phosphoserine; by GSK3-beta1 Publication1
Modified residuei349PhosphothreonineBy similarity1
Modified residuei350Phosphoserine; by MAPK11 and MAPK14By similarityCurated1
Modified residuei368Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei388PhosphoserineCombined sources1
Modified residuei566Phosphothreonine; by PDPK11 Publication1
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. 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.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ02156
PaxDbiQ02156
PeptideAtlasiQ02156
PRIDEiQ02156

PTM databases

iPTMnetiQ02156
PhosphoSitePlusiQ02156

Miscellaneous databases

PMAP-CutDBiQ02156

Expressioni

Gene expression databases

BgeeiENSG00000171132
CleanExiHS_PRKCE
ExpressionAtlasiQ02156 baseline and differential
GenevisibleiQ02156 HS

Organism-specific databases

HPAiCAB001948
HPA044496
HPA054252

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 and YWHAB (By similarity). Interacts with DGKQ and STAT3. Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (PubMed:20353823).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • 14-3-3 protein binding Source: Ensembl
  • actin monomer binding Source: UniProtKB
  • enzyme binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111567, 62 interactors
DIPiDIP-34186N
ELMiQ02156
IntActiQ02156, 15 interactors
MINTiQ02156
STRINGi9606.ENSP00000306124

Chemistry databases

BindingDBiQ02156

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WH0X-ray2.25Q/R342-372[»]
5LIHX-ray3.25F/G149-164[»]
ProteinModelPortaliQ02156
SMRiQ02156
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02156

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 actinBy similarity6

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
GeneTreeiENSGT00820000126964
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiQ02156
KOiK18050
OMAiPCDQELK
OrthoDBiEOG091G0QRS
PhylomeDBiQ02156
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

Sequencei

Sequence statusi: Complete.

Q02156-1 [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 PEGRVYVIID LSGSSGEAPK DNEERVFRER
160 170 180 190 200
MRPRKRQGAV RRRVHQVNGH KFMATYLRQP TYCSHCRDFI WGVIGKQGYQ
210 220 230 240 250
CQVCTCVVHK RCHELIITKC AGLKKQETPD QVGSQRFSVN MPHKFGIHNY
260 270 280 290 300
KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA
310 320 330 340 350
KVLADLGVTP DKITNSGQRR KKLIAGAESP QPASGSSPSE EDRSKSAPTS
360 370 380 390 400
PCDQEIKELE NNIRKALSFD NRGEEHRAAS SPDGQLMSPG ENGEVRQGQA
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
FGMCKEGILN GVTTTTFCGT PDYIAPEILQ ELEYGPSVDW WALGVLMYEM
610 620 630 640 650
MAGQPPFEAD NEDDLFESIL HDDVLYPVWL SKEAVSILKA FMTKNPHKRL
660 670 680 690 700
GCVASQNGED AIKQHPFFKE IDWVLLEQKK IKPPFKPRIK TKRDVNNFDQ
710 720 730
DFTREEPVLT LVDEAIVKQI NQEEFKGFSY FGEDLMP
Length:737
Mass (Da):83,674
Last modified:July 1, 1993 - v1
Checksum:i85032D0A091A1F7F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035466143E → K in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs772834505Ensembl.1
Natural variantiVAR_042307333A → V1 PublicationCorresponds to variant dbSNP:rs55989965Ensembl.1
Natural variantiVAR_042308389P → R1 PublicationCorresponds to variant dbSNP:rs55767130Ensembl.1
Natural variantiVAR_042309563T → M1 PublicationCorresponds to variant dbSNP:rs34077350Ensembl.1
Natural variantiVAR_050559654A → T. Corresponds to variant dbSNP:rs35777875Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X65293 mRNA Translation: CAA46388.1
EU332867 Genomic DNA Translation: ABY87556.1
U51244 Genomic DNA Translation: AAD08855.1
AC017078 Genomic DNA Translation: AAY14773.1
AC017006 Genomic DNA Translation: AAX93253.1
CH471053 Genomic DNA Translation: EAX00258.1
BC109033 mRNA Translation: AAI09034.1
BC109034 mRNA Translation: AAI09035.1
CCDSiCCDS1824.1
PIRiS28942
RefSeqiNP_005391.1, NM_005400.2
XP_005264485.1, XM_005264428.1
UniGeneiHs.580351
Hs.677120

Genome annotation databases

EnsembliENST00000306156; ENSP00000306124; ENSG00000171132
GeneIDi5581
KEGGihsa:5581
UCSCiuc002rut.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKPCE_HUMAN
AccessioniPrimary (citable) accession number: Q02156
Secondary accession number(s): B0LPH7
, Q32MQ3, Q53SL4, Q53SM5, Q9UE81
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: March 28, 2018
This is version 188 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health