PRKCH protein kinase C eta [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKCHprovided by HGNC
Official Full Name: protein kinase C etaprovided by HGNC
Primary source: HGNC:HGNC:9403
See related: Ensembl:ENSG00000027075 MIM:605437; AllianceGenome:HGNC:9403
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; uORF2; nPKC-eta
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. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]
Expression: Ubiquitous expression in lymph node (RPKM 18.8), spleen (RPKM 14.7) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q23.1

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (61187468..61550976)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (55394377..55757580)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (61788297..62017694)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PRKCH polymorphism is associated with rheumatoid arthritis in a Chinese population.
Title: PRKCH polymorphism is associated with rheumatoid arthritis in a Chinese population.
Study provides mechanistic evidence that inhibition of PKCeta isoform alleviated mitochondrial injuries and function, attenuated apoptosis, and renal fibrosis in high glucose (HG)-cultured advanced oxidation protein products (AOPPs)-induced HK-2 cells. Thus, AOPPs-induced mitochondrial dysfunction and oxidative stress cause tubulointerstitial fibrosis in diabetic nephropathy via activation of the PKCeta isoform.
Title: Advanced Oxidation Protein Products Aggravate Tubulointerstitial Fibrosis Through Protein Kinase C-Dependent Mitochondrial Injury in Early Diabetic Nephropathy.
The author show that knockdown of PKCeta caused resistance to chemotherapeutic drug-induced apoptosis and this could be explained by the induction of cellular senescence.
Title: Differential effects of protein kinase C-eta on apoptosis versus senescence.
These results suggest that PKCeta utilizes the ERK signaling pathway to protect against ubiquitin-mediated proteasomal degradation of Mcl-1
Title: Protein kinase C-eta regulates Mcl-1 level via ERK1.
PRKCH rs2230500 gene polymorphism is significantly related to the efficiency in telmisartan therapy (p = 0.02). The PRKCH rs2230500 may influence the antihypertensive efficacy of telmisartan in Chinese EH patients.
Title: Influence of PRKCH gene polymorphism on antihypertensive response to amlodipine and telmisartan.
PRKCH is highly expressed in hematopoietic stem cell (HSC) and is necessary for optimal HSC function.
Title: PRKCH regulates hematopoietic stem cell function and predicts poor prognosis in acute myeloid leukemia.
The association between PRKCH 1425G/A and lacunar infarction was independent of traditional stroke risk factors
Title: Protein kinase Cη polymorphism and the susceptibility to ischemic stroke in the Taiwan population.
Data suggest that targeted manipulation of protein kinase C isoforms PKCalpha, PKCbeta, and PKCeta might be beneficial in certain proteinuric kidney diseases with altered transient receptor potential cation channel subfamily C member 6 protein (TRPC6) functions.
Title: Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes.
variant genotypes of PRKCH 1425G/A are an independent prognostic factor for ischemic stroke in the final multivariate Cox regression model
Title: PRKCH 1425G/A Polymorphism Predicts Recurrence of Ischemic Stroke in a Chinese Population.
Meta-analysis indicated that the 1425G/A SNP in PRKCH may contribute to susceptibility of stroke, especially for ischemic stroke.
Title: A quantitative assessment of the association between 1425G/A polymorphism in PRKCH and risk of stroke.

Submit: New GeneRIF Correction See all GeneRIFs (55)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Ischemic stroke MedGen: C0948008 OMIM: 601367 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide association study for reading and language abilities in two population cohorts. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of protein kinase C, eta (PRKCH) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896	PubMed
	env	Down modulation 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	c-FLIPL inhibits Bax activation via modulating PKC expression at the transcriptional level involving AP-2 during gp120 treatment	PubMed
	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	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
Nef	nef	The N-terminus of HIV-1 Nef associates with PKC eta	PubMed
Tat	tat	Phospholipase C/protein kinase C signaling pathway-dependent phosphorylation of p44/42 and JNK MAP kinases participates partially in IL-1beta induction by TAT	PubMed
	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
matrix	gag	Protein kinase C (PKC) phosphorylates HIV-1 Matrix on serine residue 111 resulting in a shift in localization of Matrix from the cytosol to the cellular membrane, suggesting a myristoyl-protein switch regulated by PKC phosphorylation	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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D14S1245 (e-PCR)
- UniSTS:12331

SHGC-80856 (e-PCR)
- UniSTS:102505

D14S1258 (e-PCR)
- UniSTS:73838

GDB:198169 (e-PCR)
- UniSTS:156022

GDB:198171 (e-PCR)
- UniSTS:156024

GDB:198172 (e-PCR)
- UniSTS:156025

G20342 (e-PCR)
- UniSTS:10620

GDB:198175 (e-PCR)
- UniSTS:156028

A005M45 (e-PCR)
- UniSTS:10621

GDB:198176 (e-PCR)
- UniSTS:156029

GDB:198180 (e-PCR)
- UniSTS:156032

GDB:198182 (e-PCR)
- UniSTS:156034

SHGC-112178 (e-PCR)
- UniSTS:168863

SHGC-77995 (e-PCR)
- UniSTS:101539

D14S168 (e-PCR)
- UniSTS:148392

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables diacylglycerol-dependent serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
enables diacylglycerol-dependent, calcium-independent serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables small GTPase binding	IEA Inferred from Electronic Annotation more info
enables translation regulator activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of glial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of B cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of keratinocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macrophage derived foam cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein localization to plasma membrane	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of translation in response to stress	IDA Inferred from Direct Assay more info	PubMed
involved_in protein kinase C signaling	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of bicellular tight junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein kinase C eta type

Names: Protein uPEP2

NP_006246.2

EC 2.7.11.13

XP_011535256.1

EC 2.7.11.13

XP_011535257.1

EC 2.7.11.13

XP_011535259.1

EC 2.7.11.13

XP_024305429.1

EC 2.7.11.13

XP_024305430.1

EC 2.7.11.13

XP_047287541.1

EC 2.7.11.13

XP_047287542.1

EC 2.7.11.13

XP_054232361.1

EC 2.7.11.13

XP_054232362.1

EC 2.7.11.13

XP_054232363.1

EC 2.7.11.13

XP_054232364.1

EC 2.7.11.13

XP_054232365.1

EC 2.7.11.13

XP_054232366.1

EC 2.7.11.13

XP_054232367.1

EC 2.7.11.13

NCBI Reference Sequences (RefSeq)

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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

NG_011514.1 RefSeqGene

Range

4783..234180

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_006255.5 → NP_006246.2 protein kinase C eta type

See identical proteins and their annotated locations for NP_006246.2

Status: REVIEWED

Source sequence(s)

AL138996, AL355916

Consensus CDS

CCDS9752.1

UniProtKB/Swiss-Prot

B4DJN5, P24723, Q16246, Q8NE03

UniProtKB/TrEMBL

B5BU77

Related

ENSP00000329127.5, ENST00000332981.11

Conserved Domains (4) summary

cd04014
Location:8 → 140

C2_PKC_epsilon; C2 domain in Protein Kinase C (PKC) epsilon

smart00220
Location:355 → 614

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05590
Location:359 → 681

STKc_nPKC_eta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta

pfam00130
Location:246 → 298

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

61187468..61550976

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024449661.2 → XP_024305429.1 protein kinase C eta type isoform X4

Conserved Domains (2) summary

cd05590
Location:198 → 520

STKc_nPKC_eta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta

pfam00130
Location:85 → 137

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
XM_011536957.2 → XP_011535259.1 protein kinase C eta type isoform X6

Conserved Domains (4) summary

cd04014
Location:8 → 140

C2_PKC_epsilon; C2 domain in Protein Kinase C (PKC) epsilon

smart00220
Location:355 → 478

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam00130
Location:246 → 298

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

cl21453
Location:359 → 478

PKc_like; Protein Kinases, catalytic domain
XM_047431586.1 → XP_047287542.1 protein kinase C eta type isoform X5
XM_047431585.1 → XP_047287541.1 protein kinase C eta type isoform X1
XM_024449662.2 → XP_024305430.1 protein kinase C eta type isoform X4

Related

ENSP00000450981.1, ENST00000555082.6

Conserved Domains (2) summary

cd05590
Location:198 → 520

STKc_nPKC_eta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta

pfam00130
Location:85 → 137

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
XM_011536954.4 → XP_011535256.1 protein kinase C eta type isoform X2

UniProtKB/TrEMBL

B5BU77

Conserved Domains (3) summary

smart00220
Location:276 → 535

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05590
Location:280 → 602

STKc_nPKC_eta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta

pfam00130
Location:167 → 219

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
XM_011536955.2 → XP_011535257.1 protein kinase C eta type isoform X3

UniProtKB/TrEMBL

B5BU77

Conserved Domains (3) summary

smart00220
Location:275 → 534

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05590
Location:279 → 601

STKc_nPKC_eta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta

pfam00130
Location:166 → 218

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)