Reviewed, UniProtKB/Swiss-Prot Q02156 (KPCE_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein kinase C epsilon type
    EC=2.7.11.13
Alternative name(s):
    nPKC-epsilon

Gene names

Name:	PRKCE
Synonyms:	PKCE

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	737 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is calcium-independent, phospholipid-dependent, serine- and threonine-specific enzyme. PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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.
Subunit structure	Forms a ternary complex with TRIM63 and GN2BL1 By similarity. Interacts with DGKQ. Ref.7
Domain	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.
Post-translational modification	Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 C2 domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	induction of apoptosis Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.7 Inferred from direct assay. Source: UniProtKB plasma membrane Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW enzyme binding Ref.7 Inferred from physical interaction. Source: UniProtKB signal transducer activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAX	Q07812	1	EBI-706254,EBI-516580
PECAM1	P16284	1	EBI-706254,EBI-716404

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 737	737	Protein kinase C epsilon type		PRO_0000055697
Regions
	Domain	1 – 99	99	C2
	Domain	408 – 668	261	Protein kinase
	Domain	669 – 737	69	AGC-kinase C-terminal
	Zinc finger	169 – 220	52	Phorbol-ester/DAG-type 1
	Zinc finger	242 – 292	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	414 – 422	9	ATP By similarity
Sites
	Active site	532	1	Proton acceptor By similarity
	Binding site	437	1	ATP By similarity
Amino acid modifications
	Modified residue	228	1	Phosphothreonine Ref.8
	Modified residue	309	1	Phosphothreonine Ref.8 Ref.9
	Modified residue	316	1	Phosphoserine Ref.8 Ref.9
	Modified residue	329	1	Phosphoserine Ref.8
	Modified residue	337	1	Phosphoserine By similarity
	Modified residue	339	1	Phosphoserine Ref.8
	Modified residue	346	1	Phosphoserine Ref.8
	Modified residue	349	1	Phosphothreonine By similarity
	Modified residue	350	1	Phosphoserine Ref.8
	Modified residue	368	1	Phosphoserine Ref.8
	Modified residue	566	1	Phosphothreonine; by PDPK1 Ref.6
	Modified residue	703	1	Phosphothreonine; by autocatalysis Potential
	Modified residue	710	1	Phosphothreonine; by autocatalysis Potential
	Modified residue	729	1	Phosphoserine; by autocatalysis Ref.8 Ref.6
Natural variations
	Natural variant	143	1	E → K in a colorectal cancer sample; somatic mutation. Ref.10		VAR_035466
	Natural variant	333	1	A → V: dbSNP rs55989965. Ref.11		VAR_042307
	Natural variant	389	1	P → R: dbSNP rs55767130. Ref.11		VAR_042308
	Natural variant	563	1	T → M: dbSNP rs34077350. Ref.11		VAR_042309
	Natural variant	654	1	A → T: dbSNP rs35777875.		VAR_050559
Experimental info
	Mutagenesis	437	1	K → W: Abolishes activity and S-729 phosphorylation. Ref.6
	Mutagenesis	566	1	T → A: Abolishes phosphorylation by PDK1, and S-729 phosphorylation. Ref.6
	Mutagenesis	566	1	T → E: No effect on S-729 phosphorylation. Ref.6
	Mutagenesis	710	1	T → E: No effect on activity; no effect on S-729 phosphorylation. Ref.6
	Mutagenesis	729	1	S → A: Enhances T-566 dephosphorylation. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q02156-1 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 85032D0A091A1F7F	FASTA	737	83,674
	10 20 30 40 50 60 MVVFNGLLKI KICEAVSLKP TAWSLRHAVG PRPQTFLLDP YIALNVDDSR IGQTATKQKT 70 80 90 100 110 120 NSPAWHDEFV TDVCNGRKIE LAVFHDAPIG YDDFVANCTI QFEELLQNGS RHFEDWIDLE 130 140 150 160 170 180 PEGRVYVIID LSGSSGEAPK DNEERVFRER MRPRKRQGAV RRRVHQVNGH KFMATYLRQP 190 200 210 220 230 240 TYCSHCRDFI WGVIGKQGYQ CQVCTCVVHK RCHELIITKC AGLKKQETPD QVGSQRFSVN 250 260 270 280 290 300 MPHKFGIHNY KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA 310 320 330 340 350 360 KVLADLGVTP DKITNSGQRR KKLIAGAESP QPASGSSPSE EDRSKSAPTS PCDQEIKELE 370 380 390 400 410 420 NNIRKALSFD NRGEEHRAAS SPDGQLMSPG ENGEVRQGQA KRLGLDEFNF IKVLGKGSFG 430 440 450 460 470 480 KVMLAELKGK DEVYAVKVLK KDVILQDDDV DCTMTEKRIL ALARKHPYLT QLYCCFQTKD 490 500 510 520 530 540 RLFFVMEYVN GGDLMFQIQR SRKFDEPRSR FYAAEVTSAL MFLHQHGVIY RDLKLDNILL 550 560 570 580 590 600 DAEGHCKLAD FGMCKEGILN GVTTTTFCGT PDYIAPEILQ ELEYGPSVDW WALGVLMYEM 610 620 630 640 650 660 MAGQPPFEAD NEDDLFESIL HDDVLYPVWL SKEAVSILKA FMTKNPHKRL GCVASQNGED 670 680 690 700 710 720 AIKQHPFFKE IDWVLLEQKK IKPPFKPRIK TKRDVNNFDQ DFTREEPVLT LVDEAIVKQI 730 NQEEFKGFSY FGEDLMP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and expression of human protein kinase C-epsilon." Basta P., Strickland M.B., Holmes W., Loomis C.R., Ballas L.M., Burns D.J. Biochim. Biophys. Acta 1132:154-160(1992) [PubMed: 1382605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	SeattleSNPs variation discovery resource Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Regulation of novel protein kinase C epsilon by phosphorylation." Cenni V., Doeppler H., Sonnenburg E.D., Maraldi N., Newton A.C., Toker A. Biochem. J. 363:537-545(2002) [PubMed: 11964154] [Abstract] Cited for: PHOSPHORYLATION AT THR-566 AND SER-729, MUTAGENESIS OF LYS-437; THR-566; THR-710 AND SER-729.
[7]	"Translocation of diacylglycerol kinase theta from cytosol to plasma membrane in response to activation of G protein-coupled receptors and protein kinase C." van Baal J., de Widt J., Divecha N., van Blitterswijk W.J. J. Biol. Chem. 280:9870-9878(2005) [PubMed: 15632189] [Abstract] Cited for: INTERACTION WITH DGKQ.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-228; THR-309; SER-316; SER-329; SER-339; SER-346; SER-350; SER-368; THR-710 AND SER-729, MASS SPECTROMETRY.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-309 AND SER-316, MASS SPECTROMETRY.
[10]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-143.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-333; ARG-389 AND MET-563.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00024539.

PIR

S28942.

RefSeq

NP_005391.1.

UniGene

Hs.580351

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WH0	X-ray	2.25	Q/R	342-372	[»]

SMR

Q02156. Positions 1-136, 109-264, 239-295, 405-736.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q02156. 2 interactions.

STRING

Q02156.

PTM databases

PhosphoSite

Q02156.

Proteomic databases

PRIDE

Q02156.

Genome annotation databases

Ensembl

ENST00000306156; ENSP00000306124; ENSG00000171132; Homo sapiens. [Genome view]

GeneID

5581.

KEGG

hsa:5581.

UCSC

uc002rut.1. human.

Organism-specific databases

CTD

5581.

GeneCards

GC02P045790.

H-InvDB

HIX0019150.

HGNC

HGNC:9401. PRKCE.

HPA

CAB001948.

MIM

176975. gene.

PharmGKB

PA33765.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05977.

HOGENOM

HBG755340.

HOVERGEN

Q02156.

InParanoid

Q02156.

OMA

SPCDQEL.

OrthoDB

EOG9CC6KS.

PhylomeDB

Q02156.

Enzyme and pathway databases

BRENDA

2.7.11.13. 247.

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
il2_1pathway. IL2-mediated signaling events.
lysophospholipid_pathway. LPA receptor mediated events.
lpa4_pathway. LPA4-mediated signaling events.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

Q02156.

Bgee

Q02156.

CleanEx

HS_PRKCE.

Genevestigator

Q02156.

Family and domain databases

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.
IPR015745. PKC.
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.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

PANTHER

PTHR22985:SF86. PKC. 1 hit.

Pfam

PF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000551. PKC_delta. 1 hit.

PRINTS

PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

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.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

21644.

PMAP-CutDB

Q02156.

SOURCE

Search...

Entry information

Entry name

KPCE_HUMAN

Accession

Primary (citable) accession number: Q02156
Secondary accession number(s): B0LPH7 , Q32MQ3, Q53SL4, Q53SM5, Q9UE81

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	January 19, 2010
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.