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    PRKCH protein kinase C, eta [ Homo sapiens ]

    Gene ID: 5583, updated on 20-May-2012
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    Summary

    Official Symbol
    PRKCHprovided by HGNC
    Official Full Name
    protein kinase C, etaprovided by HGNC
    Primary source
    HGNC:9403
    See related
    Ensembl:ENSG00000027075; HPRD:05669; MIM:605437; Vega:OTTHUMG00000152341
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PKCL; PKC-L; PRKCL; nPKC-eta; MGC5363; MGC26269
    Summary
    Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    14q23.1
    Sequence :
    Chromosome: 14; NC_000014.8 (61788515..62017698)
    See PRKCH in Epigenomics, MapViewer

    Chromosome 14 - NC_000014.8Genomic Context describing neighboring genes Neighboring gene solute carrier family 38, member 6 Neighboring gene uncharacterized LOC100506751 Neighboring gene transmembrane protein 30B Neighboring gene uncharacterized LOC400221 Neighboring gene hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. PKCη is a negative regulator of AKT inhibiting the IGF-I induced proliferation. Shahaf G, et al. Exp Cell Res, 2012 Apr 15. PMID 22305966.
    2. Association between 1425G/A SNP in PRKCH and ischemic stroke among Chinese and Japanese populations: a meta-analysis including 3686 cases and 4589 controls. Li J, et al. Neurosci Lett, 2012 Jan 6. PMID 22044875.
    3. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    4. Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage. Raveh-Amit H, et al. Biochem Biophys Res Commun, 2011 Aug 26. PMID 21820409.
    5. Contribution of 1425G/A polymorphism in protein kinase C-Eta (PRKCH) gene and brain white matter lesions to the risk of sudden sensorineural hearing loss in a Japanese nested case-control study. Uchida Y, et al. J Neurogenet, 2011 Oct. PMID 21756056.

    See all (91) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. It was shown that the PKCeta isoform is a negative regulator of the AKT signaling pathway. The IGF-I induced phosphorylation on Ser473 of AKT was inhibited by the PKCeta-induced expression in MCF-7 breast adenocarcinoma cancer cells.
      Title: PKCη is a negative regulator of AKT inhibiting the IGF-I induced proliferation.
    2. A remarkable association of minor alleles (1425G/A and _15) in the PRKCH gene with an elevated risk of coronary artery disease and increased levels of LDL-C in a Chinese population.
      Title: The role of PRKCH gene variants in coronary artery disease in a Chinese population.
    3. The present meta-analyses suggested that 1425G/A SNP in PRKCH was associated with ischemic stroke, particularly lacunar infarction, in Chinese and Japanese populations.
      Title: Association between 1425G/A SNP in PRKCH and ischemic stroke among Chinese and Japanese populations: a meta-analysis including 3686 cases and 4589 controls.
    4. In the present study, a significant association between the PRKCH 1425G/A polymorphism and SSNHL risk was observed through a nested case-control analysis within the population-based study.
      Title: Contribution of 1425G/A polymorphism in protein kinase C-Eta (PRKCH) gene and brain white matter lesions to the risk of sudden sensorineural hearing loss in a Japanese nested case-control study.
    5. study suggests that PKCeta is involved in NF-kappaB signaling leading to drug resistance.
      Title: Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage.
    6. Catalytic activity of protein kinase C eta (PKCeta) is not necessary for enlarged and flattened morphology of differentiated human keratinocytes, although it is important for gene expression of the marker proteins.
      Title: Direct binding of RalA to PKCη and its crucial role in morphological change during keratinocyte differentiation.
    7. Three different isotypes of protein kinase C, i.e. PKC-alpha, PKC-eta and PKC-theta, were found to be regulated and translocated in opposite directions upon apoptosis induction.
      Title: Quantitative proteome analysis of detergent-resistant membranes identifies the differential regulation of protein kinase C isoforms in apoptotic T cells.
    8. the AA genotype of PRKCH, relative to the G/G genotype, may be a higher risk genotype for severe gastric atrophy
      Title: PRKCH gene polymorphism is associated with the risk of severe gastric atrophy.
    9. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: PRKCH gene polymorphism is associated with the risk of severe gastric atrophy.
    10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    Submit: New GeneRIF Correction See all (34)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Cerebral infarction, susceptibility to

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways PubMed
    env Induction of apoptosis in cell cultures through binding of HIV-1 gp120 or gp160 to CXCR4 involves protein kinase C, basic fibroblast growth factor, caspase-3, and the pro-apoptotic molecule Bax PubMed
    env HIV-1 gp120 increases the levels of calcium-dependent and -independent PKC isozymes; the most striking change is observed in PKC-zeta isozyme levels PubMed
    env Downmodulation of the interaction between HIV-1 gp120 and CD4 by TPA is blocked by protein kinase C (PKC) inhibitors, suggesting PKC may play an important role in HIV-1 infection PubMed
    env A specific interaction between CD4 and HIV-1 gp120 is required for phosphorylation of CD4, which could involve protein kinase C PubMed
    env IL-16 induces rapid translocation of PKC from the cytosol to the membrane in CD4+ cells; PKC inhibitors completely block IL-16-induced lymphocyte migration as well as the motile response induced by HIV-1 gp120 and anti-CD4 antibody binding to CD4 PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160-induced AP-1 complex formation is dependent upon protein tyrosine phosphorylation and is abolished by inhibitors of protein kinase C, but it is unaffected by calcium channel blockers or cyclosporine A PubMed
    Envelope transmembrane glycoprotein gp41 env A synthetic peptide corresponding to cytoplasmic domain residues 828-848 of HIV-1 gp41 inhibits pKC-catalysed phosphorylation of a protein substrate PubMed
    env A synthetic peptide containing residues 581-597 from HIV-1 gp41 inhibits protein kinase C (pkC)-mediated phosphorylation of the CD3 gamma-chain in intact cells and directly inhibits partially purified pkC PubMed
    Tat tat Protein kinase C is required for HIV-1 Tat-mediated transactivation of the viral LTR promoter, indicating protein kinase C regulates the process of HIV-1 transactivation and may play a role in the transition of HIV from latency to productive growth PubMed
    tat Protein kinase C phosphorylates HIV-1 Tat on serine residue 46 PubMed
    tat HIV-1 Tat activates protein kinase C, resulting in the induction of TNF-alpha, IL-6 and IL-10 expression and the secretion of MCP-1 PubMed
    retropepsin gag-pol Phosphorylation of human recombinant vimentin by PKC inhibits the proteolytic processing of the vimentin head domain by HIV-1 protease PubMed
    reverse transcriptase gag-pol HIV-1 RT heterodimer expressed in bacteria can be phosphorylated in vitro by several purified mammalian protein kinases including auto-activated protein kinase (PK), CKII, cytosolic protamine kinase (CPK), myelin basic protein kinase 1 (MBPK1), and PRKC PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_006246.2 NP_006729.4 AKAP13    BIND  PubMed AKAP-Lbc interacts with PKC-eta. This interaction was modeled on a demonstrated interaction between human AKAP-Lbc and rat PKC-eta. 
    NP_006246.2 PDPK1    BIND  PubMed An unspecified isoform of PDPK1 (PDK1) interacts with and phosphorylates PRKCH (PKC-eta). This interaction was modeled on a demonstrated interaction between PDPK1 from an unspecified species and PRKCH from an unspecified species. 
    NP_006246.2 NP_006246.2 PRKCH    BIND  PubMed PRKCH (PKC-eta) autophosphorylates. This interaction was modeled on a demonstrated interaction using PRKCH from an unspecified species. 
    NP_006246.2 NP_002733.1 PRKD1    BIND  PubMed PRKCH (PKC-eta) phosphorylates PRKD1 (PKC-mu). This interaction was modeled on a demonstrated interaction between PRKCH from an unspecified species and human PRKD1. 
    P24723 P24941 CDK2    HPRD  PubMed  
    P24723 P06241 FYN    HPRD  PubMed  
    P24723 P05107 ITGB2    HPRD  PubMed  
    P24723 P49757 NUMB    HPRD  PubMed  
    P24723 Q9NPB6 PARD6A    HPRD  PubMed  
    P24723 Q15139 PRKD1    HPRD  PubMed  
    P24723 Q06124 PTPN11    HPRD  PubMed  
    P24723 P12931 SRC    HPRD  PubMed  
    BioGRID:111569 BioGRID:107452 CDK2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111569 BioGRID:110411 MGMT    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111569 BioGRID:110852 NFE2L2    BioGRID  PubMed Biochemical Activity 
    BioGRID:111569 BioGRID:111569 PRKCH    BioGRID  PubMed Biochemical Activity 
    BioGRID:111569 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111569 BioGRID:130893 ZBTB8OS    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Calcium Regulation in the Cardiac Cell, organism-specific biosystem (from WikiPathways)
      Calcium Regulation in the Cardiac Cell, organism-specific biosystemCalcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resu...
    • Effects of PIP2 hydrolysis, organism-specific biosystem (from REACTOME)
      Effects of PIP2 hydrolysis, organism-specific biosystemHydrolysis of phosphatidyl inositol-bisphosphate (PIP2) by phospholipase C (PLC) produces diacylglycerol (DAG) and inositol triphosphate (IP3). Both are potent second messengers. IP3 diffuses into th...
    • Endothelins, organism-specific biosystem (from Pathway Interaction Database)
      Endothelins, organism-specific biosystem
      Endothelins
    • G Protein Signaling Pathways, organism-specific biosystem (from WikiPathways)
      G Protein Signaling Pathways, organism-specific biosystemG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades. G proteins are so called because they function as "molecular switches". They...
    • G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
    • G alpha (z) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (z) signalling events, organism-specific biosystemThe heterotrimeric G protein Gz, is a member of the Gi family. Unlike other Gi family members it lacks an ADP ribosylation site cysteine four residues from the carboxyl terminus and is thus pertussis...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Insulin Signaling, organism-specific biosystem (from WikiPathways)
      Insulin Signaling, organism-specific biosystem
      Insulin Signaling
    • MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
      Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • Role of Calcineurin-dependent NFAT signaling in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
      Role of Calcineurin-dependent NFAT signaling in lymphocytes, organism-specific biosystem
      Role of Calcineurin-dependent NFAT signaling in lymphocytes
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Thromboxane A2 receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
      Thromboxane A2 receptor signaling, organism-specific biosystem
      Thromboxane A2 receptor signaling
    • Tight junction, organism-specific biosystem (from KEGG)
      Tight junction, organism-specific biosystemEpithelial tight junctions (TJs) are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic 'plaque' consisting of ma...
    • Tight junction, conserved biosystem (from KEGG)
      Tight junction, conserved biosystemEpithelial tight junctions (TJs) are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic 'plaque' consisting of ma...
    • Vascular smooth muscle contraction, organism-specific biosystem (from KEGG)
      Vascular smooth muscle contraction, organism-specific biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • Vascular smooth muscle contraction, conserved biosystem (from KEGG)
      Vascular smooth muscle contraction, conserved biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • Wnt Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell pluri...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein kinase C activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    blood coagulation TAS
    Traceable Author Statement
    more info
    		  
    cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of glial cell apoptosis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    platelet activation TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of B cell receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of NF-kappaB transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		  
    positive regulation of glial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of keratinocyte differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of macrophage derived foam cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    protein phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    regulation of tight junction assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    protein kinase C eta type
    Names
    protein kinase C eta type
    NP_006246.2
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011514.1 RefSeqGene

      Range
      5001..234184
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006255.3 → NP_006246.2  protein kinase C eta type

      Status: REVIEWED

      Source sequence(s)
      BC037268, CA447784, CB994021, CD522081, M55284
      Consensus CDS
      CCDS9752.1
      UniProtKB/Swiss-Prot
      P24723
      Related
      ENSP00000329127, OTTHUMP00000179058, ENST00000332981, OTTHUMT00000276974
      Conserved Domains (4) summary
      cd00029
      Location:246 – 295
      Blast Score: 161
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      cd05590
      Location:359 – 678
      Blast Score: 1820
      STKc_nPKC_eta; Catalytic domain of the Protein Serine/Threonine Kinase, Novel Protein Kinase C eta
      cd04014
      Location:8 – 140
      Blast Score: 542
      C2_PKC_epsilon; C2 domain in Protein Kinase C (PKC) epsilon
      smart00220
      Location:355 – 614
      Blast Score: 777
      S_TKc; Serine/Threonine protein kinases, catalytic domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000014.8 Reference GRCh37.p5 Primary Assembly

      Range
      61788515..62017698
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000146.1 Alternate HuRef

      Range
      41951908..42181287
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AF045569.1 AAD12779.1
    genomic AL138996.4 (3143..182266) None
    genomic AL355916.2 (120939..170998) None
    genomic CH471061.1 EAW80800.1
      EAW80801.1
      EAW80802.1
    genomic CQ834780.1 CAH05605.1
    genomic HI574284.1 CBX47631.1
    mRNA AB451313.1 BAG70127.1
    mRNA AK093241.1 None
    mRNA AK290183.1 BAF82872.1
    mRNA AK296158.1 BAG58897.1
    mRNA AK300864.1 BAG62513.1
    mRNA AX775931.1 CAE11665.1
    mRNA AX775933.1 CAE11666.1
    mRNA BC001000.2 AAH01000.1
    mRNA BC037268.1 AAH37268.1
    mRNA CA447784.1 None
    mRNA CB994021.1 None
    mRNA CD522081.1 None
    mRNA M55284.1 AAA60100.1
    mRNA S74620.1 AAB32724.1
    other-genetic DQ890890.2 ABM81816.1
    other-genetic DQ894045.2 ABM84971.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P24723.4 GenPept UniProtKB/Swiss-Prot:P24723
    Q71UV9 GenPept UniProtKB/TrEMBL:Q71UV9
    Q9BVQ0 GenPept UniProtKB/TrEMBL:Q9BVQ0
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

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