Reviewed, UniProtKB/Swiss-Prot P24723 (KPCL_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	PRKCH
Synonyms:	PKCL, PRKCL

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	683 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-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation.
Subunit structure	Interacts with DGKQ. Ref.8
Tissue specificity	Most abundant in lung, less in heart and skin.
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.
Involvement in disease	Defects in PRKCH may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
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	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.8 Inferred from direct assay. Source: UniProtKB plasma membrane Ref.8 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW enzyme binding Ref.8 Inferred from physical interaction. Source: UniProtKB protein kinase C activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 683

683

Protein kinase C eta type

PRO_0000055705

Regions

Domain

12 – 113

102

C2

Domain

355 – 614

260

Protein kinase

Domain

615 – 683

69

AGC-kinase C-terminal

Zinc finger

171 – 222

52

Phorbol-ester/DAG-type 1

Zinc finger

245 – 295

51

Phorbol-ester/DAG-type 2

Nucleotide binding

361 – 369

9

ATP By similarity

Sites

Active site

479

1

Proton acceptor By similarity

Binding site

384

1

ATP By similarity

Amino acid modifications

Modified residue

28

1

Phosphoserine; by autocatalysis Probable

Modified residue

32

1

Phosphoserine; by autocatalysis Probable

Modified residue

57

1

Phosphothreonine

Modified residue

317

1

Phosphoserine Ref.9 Ref.11

Modified residue

320

1

Phosphoserine Ref.9

Modified residue

513

1

Phosphothreonine Probable

Modified residue

656

1

Phosphothreonine Probable

Modified residue

675

1

Phosphoserine

Natural variations

Natural variant

19

1

A → V: dbSNP rs55645551. Ref.14

VAR_042312

Natural variant

65

1

K → R: dbSNP rs55737090. Ref.14

VAR_042313

Natural variant

149

1

R → Q: dbSNP rs55848048. Ref.14

VAR_042314

Natural variant

359

1

R → Q: dbSNP rs55818778. Ref.14

VAR_042315

Natural variant

374

1

V → I Associated with susceptibility to ischemic stroke; increases autophosphorylation and kinase activity. dbSNP rs2230500. Ref.14 Ref.13

VAR_034604

Natural variant

497

1

D → Y: dbSNP rs11846991.

VAR_060736

Natural variant

575

1

T → A in a aLL TEL/AML1+ sample; somatic mutation. Ref.14

VAR_042316

Natural variant

594

1

T → I in a colorectal adenocarcinoma sample; somatic mutation. Ref.14

VAR_042317

Natural variant

612

1

P → S: dbSNP rs34159231. Ref.14

VAR_042318

Natural variant

645

1

D → V: dbSNP rs35561533.

VAR_042438

Experimental info

Sequence conflict

96

1

Missing in AAA60100. Ref.1

Sequence conflict

109

1

L → R in AAA60100. Ref.1

Sequence conflict

110

1

R → G in AAA60100. Ref.1

Sequence conflict

393

1

Q → L in AAA60100. Ref.1

Sequence conflict

472

1

D → E in AAB32724. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

683

Helix Strand Turn

Details...

Beta strand

12 – 16

5

Helix

26 – 31

6

Beta strand

43 – 49

7

Beta strand

70 – 74

5

Beta strand

82 – 88

7

Beta strand

96 – 103

8

Helix

105 – 111

7

Beta strand

116 – 118

3

Beta strand

133 – 136

4

Sequences

	Sequence		Length	Mass (Da)
	P24723-1 [UniParc]. Last modified December 15, 2009. Version 4. Checksum: 0A29806CE31912F2	FASTA	683	77,828
	10 20 30 40 50 60 MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK 70 80 90 100 110 120 QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TTGASDTFEG 130 140 150 160 170 180 WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQIN GHKFMATYLR 190 200 210 220 230 240 QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDSKIAEQRF 250 260 270 280 290 300 GINIPHKFSI HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV 310 320 330 340 350 360 ELAKTLAGMG LQPGNISPTS KLVSRSTLRR QGKESSKEGN GIGVNSSNRL GIDNFEFIRV 370 380 390 400 410 420 LGKGSFGKVM LARVKETGDL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF 430 440 450 460 470 480 CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HDKGIIYRDL 490 500 510 520 530 540 KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM 550 560 570 580 590 600 GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL 610 620 630 640 650 660 TQGGEHAILR HPFFKEIDWA QLNHRQIEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE 670 680 GHLPMINQDE FRNFSYVSPE LQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of PKC-L, a new member of the protein kinase C-related gene family specifically expressed in lung, skin, and heart." Bacher N., Zisman Y., Berent E., Livneh E. Mol. Cell. Biol. 11:126-133(1991) [PubMed: 1986216] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	Erratum Bacher N., Zisman Y., Berent E., Livneh E. Mol. Cell. Biol. 12:1404-1404(1992) [PubMed: 1545821] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[4]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Testis.
[7]	"Identification of multiple, novel, protein kinase C-related gene products." Palmer R.H., Ridden J., Parker P.J. FEBS Lett. 356:5-8(1994) [PubMed: 7988719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 438-539.
[8]	"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.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317 AND SER-320, MASS SPECTROMETRY.
[10]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57; SER-317 AND SER-675, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites." Littler D.R., Walker J.R., She Y.-M., Finerty P.J. Jr., Newman E.M., Dhe-Paganon S. Biochem. Biophys. Res. Commun. 349:1182-1189(2006) [PubMed: 16973127] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-138, PHOSPHORYLATION AT SER-28 AND SER-32, MASS SPECTROMETRY.
[13]	"A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction." Kubo M., Hata J., Ninomiya T., Matsuda K., Yonemoto K., Nakano T., Matsushita T., Yamazaki K., Ohnishi Y., Saito S., Kitazono T., Ibayashi S., Sueishi K., Iida M., Nakamura Y., Kiyohara Y. Nat. Genet. 39:212-217(2007) [PubMed: 17206144] [Abstract] Cited for: ASSOCIATION OF VARIANT ILE-374 WITH ISCHEMIC STROKE, CHARACTERIZATION OF VARIANT ILE-374.
[14]	"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-19; ARG-65; GLN-149; GLN-359; ILE-374; ALA-575; ILE-594 AND SER-612.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M55284 mRNA. Translation: AAA60100.1.
AK290183 mRNA. Translation: BAF82872.1.
AL138996 Genomic DNA. No translation available.
AL355916 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80801.1.
BC037268 mRNA. Translation: AAH37268.1.
S74620 mRNA. Translation: AAB32724.1.

IPI

IPI00184572.

PIR

A39666.

RefSeq

NP_006246.2.

UniGene

Hs.333907

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FK9	X-ray	1.75	A	1-138	[»]

SMR

P24723. Positions 117-266, 239-302, 326-557, 352-683.

ModBase

Search...

Protein-protein interaction databases

STRING

P24723.

PTM databases

PhosphoSite

P24723.

Proteomic databases

PRIDE

P24723.

Genome annotation databases

Ensembl

ENST00000332981; ENSP00000329127; ENSG00000027075; Homo sapiens. [Genome view]

GeneID

5583.

KEGG

hsa:5583.

UCSC

uc001xfn.1. human.

Organism-specific databases

CTD

5583.

GeneCards

GC14P060858.

HGNC

HGNC:9403. PRKCH.

HPA

CAB001998.

MIM

601367. phenotype.
605437. gene.

PharmGKB

PA33767.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15488.

HOGENOM

HBG755340.

HOVERGEN

P24723.

InParanoid

P24723.

Enzyme and pathway databases

BRENDA

2.7.11.13. 247.

Pathway_Interaction_DB

endothelinpathway. Endothelins.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
txa2pathway. Thromboxane A2 receptor signaling.

Gene expression databases

ArrayExpress

P24723.

Bgee

P24723.

CleanEx

HS_PRKCH.

Genevestigator

P24723.

GermOnline

ENSG00000027075. Homo sapiens.

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

21652.

SOURCE

Search...

Entry information

Entry name

KPCL_HUMAN

Accession

Primary (citable) accession number: P24723
Secondary accession number(s): Q16246, Q8NE03

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	December 15, 2009
Last modified:	February 9, 2010
This is version 108 of the entry and version 4 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.