Reviewed,
UniProtKB/Swiss-Prot P24723 (KPCL_HUMAN)
Last modified
July 7, 2009.
Version 100.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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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 |
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| 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. |
| Sequence processing | The displayed sequence is not processed. |
| 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. |
| 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 | 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.1Traceable author statement. Source: ProtInc |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol bindingInferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Ref.1Traceable author statement. Source: ProtInc zinc ion bindingInferred 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 | 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 | ||||||
Sequences
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References
| « Hide '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. |
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 | |||||||||||||
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| 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... | ||||||||||||
Entry information
| Entry name | KPCL_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P24723 Secondary accession number(s): Q16246, Q8NE03 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 14 Human chromosome 14: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


