Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein kinase C epsilon type

Gene

PRKCE

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

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-565 (activation loop of the kinase domain), Thr-709 (turn motif) and Ser-728 (hydrophobic region), need to be phosphorylated for its full activation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei436ATPPROSITE-ProRule annotation1
Active sitei531Proton 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 bindingi413 – 421ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell adhesion, Cell cycle, Cell division, Immunity

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 1749.

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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity
  • Cytoplasmcytoskeleton By similarity
  • Cell membrane By similarity
  • Cytoplasmperinuclear region By similarity
  • Nucleus By similarity

  • Note: Translocated to plasma membrane in epithelial cells stimulated by HGF. Associated with the Golgi at the perinuclear site in pre-passage fibroblasts. In passaging cells, translocated to the cell periphery. Translocated to the nucleus in PMA-treated cells (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000556991 – 736Protein kinase C epsilon typeAdd BLAST736

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62PhosphoserineBy similarity1
Modified residuei228PhosphothreonineBy similarity1
Modified residuei234PhosphoserineBy similarity1
Modified residuei309PhosphothreonineBy similarity1
Modified residuei316PhosphoserineBy similarity1
Modified residuei329PhosphoserineBy similarity1
Modified residuei337PhosphoserineBy similarity1
Modified residuei346Phosphoserine; by GSK3-betaBy similarity1
Modified residuei349PhosphothreonineBy similarity1
Modified residuei350Phosphoserine; by MAPK11 and MAPK14By similarity1
Modified residuei368Phosphoserine; by autocatalysisBy similarity1
Modified residuei388PhosphoserineBy similarity1
Modified residuei565Phosphothreonine; by PDPK1By similarity1
Modified residuei702Phosphothreonine; by autocatalysisSequence analysis1
Modified residuei709Phosphothreonine; by autocatalysisSequence analysisBy similarity1
Modified residuei728Phosphoserine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylation on Thr-565 by PDPK1 triggers autophosphorylation on Ser-728. 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 similarity).By similarity

Keywords - PTMi

Phosphoprotein

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, STAT3 and YWHAB (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000011861.

Structurei

3D structure databases

ProteinModelPortaliP10830.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 99C2PROSITE-ProRule annotationAdd BLAST99
Domaini407 – 667Protein kinasePROSITE-ProRule annotationAdd BLAST261
Domaini668 – 736AGC-kinase C-terminalAdd BLAST69

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

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 2 phorbol-ester/DAG-type zinc fingers.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

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.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiP10830.
KOiK18050.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501106. Protein_kin_C_epsilon. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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. 1 hit.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P10830-1 [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 RCHELIITKV AGLKKQETPD EVGSQRFSVN MPHKFGIHNY
260 270 280 290 300
KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA
310 320 330 340 350
KVLADLGVTP DKITNSGQRR KKLIGGAESP QPTSGSSPSE EDRSKSAPTS
360 370 380 390 400
PCDQELKELE NNIRKALSFD NRGEEHRAAS STDGQLGSPE NGEVRQGQAK
410 420 430 440 450
RLGLDEFNFI KVLGKGSFGK VMLAELKGKD EVYAVKVLKK DVILQDDDVD
460 470 480 490 500
CTMTEKRILA LARKHPYLTQ LYCCFQTKDR LFFVMEYVNG GDLMFQIQRS
510 520 530 540 550
RKFDEPRSRF YAAEVTSALM FLHQHGVIYR DLKLDNILLD AEGHCKLADF
560 570 580 590 600
GMCKEGILNG VTTTTFCGTP DYIAPEILQE LEYGPSVDWW ALGVLMYEMM
610 620 630 640 650
AGQPPFEADN EDDLFESILH DDVLYPVWLS KEAVSILKAF MTKNPHKRLG
660 670 680 690 700
CVAAQNGEDA IKQHPFFKEI DWVLLEQKKI KPPFKPRIKT KRDVNNFDQD
710 720 730
FTREEPVLTL VDEAIVKQIN QEEFKGFSYF GEDLMP
Length:736
Mass (Da):83,516
Last modified:July 1, 1989 - v1
Checksum:i261C4FEE59E9BFEB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20014 mRNA. Translation: AAA31426.1.
PIRiA29880. KIRBCE.
RefSeqiNP_001075743.1. NM_001082274.1.
UniGeneiOcu.1940.

Genome annotation databases

GeneIDi100009103.
KEGGiocu:100009103.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20014 mRNA. Translation: AAA31426.1.
PIRiA29880. KIRBCE.
RefSeqiNP_001075743.1. NM_001082274.1.
UniGeneiOcu.1940.

3D structure databases

ProteinModelPortaliP10830.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000011861.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009103.
KEGGiocu:100009103.

Organism-specific databases

CTDi5581.

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiP10830.
KOiK18050.

Enzyme and pathway databases

BRENDAi2.7.11.13. 1749.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501106. Protein_kin_C_epsilon. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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. 1 hit.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPCE_RABIT
AccessioniPrimary (citable) accession number: P10830
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 136 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.