Protein kinase C eta type - Homo sapiens (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

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Protein attributes

Sequence length	683 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.
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.

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Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Phorbol-ester binding 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
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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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

513

1

Phosphothreonine Probable

Modified residue

656

1

Phosphothreonine Probable

Modified residue

675

1

Phosphoserine Probable

Natural variations

Natural variant

19

1

A → V Ref.9

VAR_042312

Natural variant

65

1

K → R Ref.9

VAR_042313

Natural variant

149

1

R → Q Ref.9

VAR_042314

Natural variant

359

1

R → Q Ref.9

VAR_042315

Natural variant

374

1

V → I Associated with susceptibility to ischemic stroke; increases autophosphorylation and kinase activity. dbSNP rs2230500. Ref.9 Ref.8

VAR_034604

Natural variant

575

1

T → A in a aLL TEL/AML1+ sample; somatic mutation. Ref.9

VAR_042316

Natural variant

594

1

T → I in a colorectal adenocarcinoma sample; somatic mutation. Ref.9

VAR_042317

Natural variant

612

1

P → S Ref.9

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

R → V in AAA60100. Ref.1

Sequence conflict

393

1

Q → L in AAA60100. Ref.1

Sequence conflict

472

1

D → E in AAB32724. Ref.6

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Sequences

Sequence

Length

Mass (Da)

Tools

P24723-1 [UniParc].

Last modified April 8, 2008. Version 3.
Checksum: AA329B696C3F3154
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FASTA

683

77,772

        10         20         30         40         50         60 
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK 

        70         80         90        100        110        120 
QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELRG 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

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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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[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. Venter J.C. Submitted (JUL-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]. Tissue: Testis.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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. 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.

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Cross-references

Sequence databases

M55284 mRNA. Translation: AAA60100.1.
AK290183 mRNA. Translation: BAF82872.1.
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

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

SMR

P24723. Positions 2-136.

ModBase

Search...

PTM databases

PhosphoSite

P24723.

Proteomic databases

PRIDE

P24723.

Genome annotation databases

Ensembl

ENSG00000027075. Homo sapiens. [Contig view]

GeneID

5583.

KEGG

hsa:5583.

UCSC

uc001xfn.1. human.

Organism-specific databases

GeneCards

GC14P060858.

HGNC

HGNC:9403. PRKCH.

HPA

CAB001998.

MIM

601367. phenotype.
605437. gene.

PharmGKB

PA33767.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

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.

GermOnline

ENSG00000027075. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR000008. C2_Ca-dep.
IPR018029. C2_membr_targeting.
IPR002219. DAG_PE_bd.
IPR015745. PKC.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[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]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00109. C1. 2 hits.
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...

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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:	April 8, 2008
Last modified:	July 7, 2009
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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