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UniProtKB/Swiss-Prot entry P24723


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name KPCL_HUMAN
Primary accession number P24723
Secondary accession numbers Q16246 Q8NE03
Integrated into Swiss-Prot on March 1, 1992
Sequence was last modified on April 8, 2008 (Sequence version 3)
Annotations were last modified on    November 25, 2008 (Entry version 91)
Name and origin of the protein
Protein name Protein kinase C eta type
Synonyms EC 2.7.11.13
nPKC-eta
PKC-L
Gene name
Name: PRKCH
Synonyms: PKCL, PRKCL
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Lung;
PubMed=1986216 [NCBI, ExPASy, EBI, Israel, Japan]
Bacher N., Zisman Y., Berent E., Livneh E.;
"Isolation and characterization of PKC-L, a new member of the protein kinase C-related gene family specifically expressed in lung, skin, and heart.";
Mol. Cell. Biol. 11:126-133(1991).
[2]
ERRATUM, AND SEQUENCE REVISION.
PubMed=1545821 [NCBI, ExPASy, EBI, Israel, Japan]
Bacher N., Zisman Y., Berent E., Livneh E.;
Mol. Cell. Biol. 12:1404-1404(1992).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Thalamus;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Testis;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 438-539.
DOI=10.1016/0014-5793(94)01202-4; PubMed=7988719 [NCBI, ExPASy, EBI, Israel, Japan]
Palmer R.H., Ridden J., Parker P.J.;
"Identification of multiple, novel, protein kinase C-related gene products.";
FEBS Lett. 356:5-8(1994).
[7]
X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-138, PHOSPHORYLATION AT SER-28 AND SER-32, AND MASS SPECTROMETRY.
DOI=10.1016/j.bbrc.2006.08.160; PubMed=16973127 [NCBI, ExPASy, EBI, Israel, Japan]
Littler D.R., Walker J.R., She Y.-M., Finerty P.J. Jr., Newman E.M., Dhe-Paganon S.;
"Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites.";
Biochem. Biophys. Res. Commun. 349:1182-1189(2006).
[8]
ASSOCIATION OF VARIANT ILE-374 WITH ISCHEMIC STROKE, AND CHARACTERIZATION OF VARIANT ILE-374.
DOI=10.1038/ng1945; PubMed=17206144 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction.";
Nat. Genet. 39:212-217(2007).
[9]
VARIANTS [LARGE SCALE ANALYSIS] VAL-19; ARG-65; GLN-149; GLN-359; ILE-374; ALA-575; ILE-594 AND SER-612.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
  • FUNCTION: This is calcium-independent, phospholipid-dependent, serine- and threonine-specific enzyme.
  • FUNCTION: 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.
  • 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.
  • SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
  • SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
  • SIMILARITY: Contains 1 C2 domain.
  • SIMILARITY: Contains 2 phorbol-ester/DAG-type zinc fingers.
  • SIMILARITY: Contains 1 protein kinase domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M55284; AAA60100.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK290183; BAF82872.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471061; EAW80801.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC037268; AAH37268.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S74620; AAB32724.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A39666; A39666.
RefSeq NP_006246.2; -.
UniGene Hs.333907
3D structure databases
PDB
2FK9; X-ray; 1.75 A; A=1-138.[ExPASy / RCSB / EBI]
PDBsum 2FK9; -.
SMR P24723; 2-136.
ModBase P24723.
PTM databases
PhosphoSite P24723; -.
Organism-specific databases
HGNC HGNC:9403; PRKCH.
GenAtlas PRKCH.
HPA CAB001998; -.
MIM 601367; phenotype. [NCBI / EBI]
605437; gene. [NCBI / EBI]
PharmGKB PA33767; -.
GeneCards P24723.
Gene expression databases
ArrayExpress P24723; -.
CleanEx HS_PRKCH; -.
GermOnline ENSG00000027075; Homo sapiens.
Ontologies
GO
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0019992; Molecular function: diacylglycerol binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004697; Molecular function: protein kinase C activity (traceable author statement from ProtInc).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0007242; Biological process: intracellular signaling cascade (inferred from electronic annotation from InterPro).
GO:0006468; Biological process: protein amino acid phosphorylation (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR002219; DAG_PE_bd.
IPR015745; PKC.
IPR000961; Pkinase_C.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.
PANTHER PTHR22985:SF86; PKC; 1.
Pfam PF00130; C1_1; 2.
PF00069; Pkinase; 1.
PF00433; Pkinase_C; 1.
Pfam graphical view of domain structure.
PRINTS PR00360; C2DOMAIN.
PR00008; DAGPEDOMAIN.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00109; C1; 2.
SM00239; C2; 1.
SM00133; S_TK_X; 1.
SM00220; S_TKc; 1.
SMART graphical view of domain structure.
PROSITE PS51285; AGC_KINASE_CTER; 1.
PS50004; C2; 1.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PS00479; ZF_DAG_PE_1; 2.
PS50081; ZF_DAG_PE_2; 2.
PROSITE graphical view of domain structure (profiles).
ProtoNet P24723.
Genome annotation databases
Ensembl ENSG00000027075; Homo sapiens. [Contig view]
GeneID 5583; -.
KEGG hsa:5583; -.
Phylogenomic databases
HOVERGEN P24723; -.
Other
LinkHub P24723; -.
NextBio 21652; -.
SOURCE PRKCH; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Kinase; Metal-binding; Nucleotide-binding; Phorbol-ester binding; Phosphoprotein; Polymorphism; Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   683  683     Protein kinase C eta type. PRO_0000055705
DOMAIN   12   113  102     C2. 
DOMAIN   355   614  260     Protein kinase. 
DOMAIN   615   683  69     AGC-kinase C-terminal. 
ZN_FING   171   222  52     Phorbol-ester/DAG-type 1. 
ZN_FING   245   295  51     Phorbol-ester/DAG-type 2. 
NP_BIND   361   369  9     ATP (By similarity). 
ACT_SITE   479   479        Proton acceptor (By similarity). 
BINDING   384   384        ATP (By similarity). 
MOD_RES   28    28        Phosphoserine; by autocatalysis (Probable). 
MOD_RES   32    32        Phosphoserine; by autocatalysis (Probable). 
MOD_RES   513   513        Phosphothreonine (Probable). 
MOD_RES   656   656        Phosphothreonine (Probable). 
MOD_RES   675   675        Phosphoserine (Probable). 
VARIANT   19    19  1     A -> V. VAR_042312 [3D]
VARIANT   65    65  1     K -> R. VAR_042313 [3D]
VARIANT   149   149  1     R -> Q. VAR_042314 
VARIANT   359   359  1     R -> Q. VAR_042315 
VARIANT   374   374  1     V -> I (associated with susceptibility to ischemic stroke; increases autophosphorylation and kinase activity). VAR_034604 
VARIANT   575   575  1     T -> A (in a aLL TEL/AML1+ sample; somatic mutation). VAR_042316 
VARIANT   594   594  1     T -> I (in a colorectal adenocarcinoma sample; somatic mutation). VAR_042317 
VARIANT   612   612  1     P -> S. VAR_042318 
VARIANT   645   645  1     D -> V (in dbSNP:rs35561533 [NCBI]). VAR_042438 
CONFLICT   96    96        Missing (in Ref. 1; AAA60100). 
CONFLICT   109   109        R -> V (in Ref. 1; AAA60100). 
CONFLICT   393   393        Q -> L (in Ref. 1; AAA60100). 
CONFLICT   472   472        D -> E (in Ref. 6; AAB32724). 
Sequence information
Length: 683 AA [This is the length of the unprocessed precursor] Molecular weight: 77772 Da [This is the MW of the unprocessed precursor] CRC64: AA329B696C3F3154 [This is a checksum on the sequence]
        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 

P24723 in FASTA format

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