PRKCG protein kinase C gamma [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKCGprovided by HGNC
Official Full Name: protein kinase C gammaprovided by HGNC
Primary source: HGNC:HGNC:9402
See related: Ensembl:ENSG00000126583 MIM:176980
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: PKCC; PKCG; SCA14; PKCI(3); PKCgamma; PKC-gamma
Summary: Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 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 distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
Expression: Biased expression in brain (RPKM 15.6) and testis (RPKM 1.4) See more
Orthologs: mouse all

Genomic context

Location:: 19q13.42

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (53882197..53907652)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (54385467..54410906)

Chromosome 19 - NC_000019.10 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
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?

Dominant negative mechanism due to truncated peptides produced by p.R76X underlies spinocerebellar ataxia type 14. PKCgamma(R76X)-GFP inhibited PKC phosphorylation activity and caused apoptosis in neurons.
Title: Spinocerebellar ataxia type 14 caused by a nonsense mutation in the PRKCG gene.
This study presented one of the largest SCA14 cohorts of patients reported contributing with novel variants and supporting the distinct phenotype spectrum with specific cellular defects resulting from different types of PRKCG mutations.
Title: Genotype-phenotype correlations, dystonia and disease progression in spinocerebellar ataxia type 14.
This study demonstrated that a combination of both, loss-of-function and gain-of-function mechanisms are likely to underlie the pathogenesis of SCA14, caused by mutations in the C1 domain of PKCgamma
Title: Neurodegeneration in SCA14 is associated with increased PKCγ kinase activity, mislocalization and aggregation.
This review showed that the PKC Gamma signaling related genes and calcium signaling related genes then discuss their role for both Purkinje cell dendritic development and cerebellar ataxia.
Title: Calcium Signaling, PKC Gamma, IP3R1 and CAR8 Link Spinocerebellar Ataxias and Purkinje Cell Dendritic Development.
SUMOylation of EphB1 repressed activation of its downstream signaling molecule PKC-gamma, and consequently inhibited neuroblastoma tumorigenesis.
Title: Sumoylation of EphB1 Suppresses Neuroblastoma Tumorigenesis via Inhibiting PKCγ Activation.
two out of three known mutations in the catalytic domain of PKCgamma did indeed show increased biological activity.
Title: Increased biological activity of protein Kinase C gamma is not required in Spinocerebellar ataxia 14.
Lysophosphatidylcholines prime polymorphonuclear neutrophil through Hck-dependent activation of PKCdelta, which stimulates PKCgamma, resulting in translocation of phosphorylated p47(phox).
Title: LysoPCs induce Hck- and PKCδ-mediated activation of PKCγ causing p47phox phosphorylation and membrane translocation in neutrophils.
The gene-environment combination of PRKCG rs3745406 C allele, BDNF rs6265 G allele and high level of negative life events was significantly associated with major depressive disorder.
Title: The interaction of combined effects of the BDNF and PRKCG genes and negative life events in major depressive disorder.
The results showed that carrier of rs454006*C allele and rs3745406*C might elevate the risk of osteosarcoma
Title: Genetic variations in the PRKCG gene and osteosarcoma risk in a Chinese population: a case-control study.
Data suggest that PRKCG (protein kinase C gamma) phosphorylates TA isoforms of p63 (tumor protein p63) at Thr157 to stabilize them and promote cell apoptosis in tumor cells.
Title: PKCδ stabilizes TAp63 to promote cell apoptosis.

Submit: New GeneRIF Correction See all GeneRIFs (56)

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
Spinocerebellar ataxia type 14 MedGen: C1854369 OMIM: 605361 GeneReviews: Hereditary Ataxia Overview, Spinocerebellar Ataxia Type 14	Compare labs

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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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	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	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	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	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

ECD09274 (e-PCR)
- UniSTS:290318

ECD15193 (e-PCR)
- UniSTS:296210

ECD18784 (e-PCR)
- UniSTS:299794

ECD12883 (e-PCR)
- UniSTS:293914

ECD17263 (e-PCR)
- UniSTS:298276

ECD21380 (e-PCR)
- UniSTS:302377

WI-20598 (e-PCR)
- UniSTS:52009

D8S2279 (e-PCR)
- UniSTS:473907

ECD11375 (e-PCR)
- UniSTS:292411

ECD05203 (e-PCR)
- UniSTS:286269

D19S206 (e-PCR), detects polymorphism
- UniSTS:13384

ECD03680 (e-PCR)
- UniSTS:284760

ECD21699 (e-PCR)
- UniSTS:302693

ECD13740 (e-PCR)
- UniSTS:294766

ECD21216 (e-PCR)
- UniSTS:302213

ECD15565 (e-PCR)
- UniSTS:296582

ECD23790 (e-PCR)
- UniSTS:304774

ECD09146 (e-PCR)
- UniSTS:290191

ECD23287 (e-PCR)
- UniSTS:304271

D19S605 (e-PCR), detects polymorphism
- UniSTS:65942

ECD08906 (e-PCR)
- UniSTS:289953

ECD07128 (e-PCR)
- UniSTS:288185

ECD16403 (e-PCR)
- UniSTS:297418

ECD21287 (e-PCR)
- UniSTS:302284

D19S926 (e-PCR)
- UniSTS:68569

ECD23376 (e-PCR)
- UniSTS:304360

ECD04606 (e-PCR)
- UniSTS:285678

PRKCG (e-PCR)
- UniSTS:266737

ECD22364 (e-PCR)
- UniSTS:303352

ECD13624 (e-PCR)
- UniSTS:294652

Homology

Homologs of the PRKCG gene: The PRKCG gene is conserved in chimpanzee, dog, cow, mouse, rat, zebrafish, and frog.
Orthologs from Annotation Pipeline: 165 organisms have orthologs with human gene PRKCG
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
calcium-dependent protein kinase C activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase C activity	TAS Traceable Author Statement more info	PubMed
protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein serine/threonine/tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
chemosensory behavior	IEA Inferred from Electronic Annotation more info
innervation	IEA Inferred from Electronic Annotation more info
intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
learning or memory	IEA Inferred from Electronic Annotation more info
negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of proteasomal protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phosphorylation	IDA Inferred from Direct Assay more info	PubMed
platelet activation	TAS Traceable Author Statement more info
positive regulation of mismatch repair	IDA Inferred from Direct Assay more info	PubMed
presynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
protein autophosphorylation	IEA Inferred from Electronic Annotation more info
protein phosphorylation	TAS Traceable Author Statement more info	PubMed
regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
regulation of phagocytosis	IEA Inferred from Electronic Annotation more info
regulation of response to food	ISS Inferred from Sequence or Structural Similarity more info
regulation of synaptic vesicle exocytosis	IEA Inferred from Electronic Annotation more info
response to morphine	ISS Inferred from Sequence or Structural Similarity more info
response to pain	ISS Inferred from Sequence or Structural Similarity more info
response to psychosocial stress	IEA Inferred from Electronic Annotation more info
rhythmic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
calyx of Held	IEA Inferred from Electronic Annotation more info
cell-cell junction	IEA Inferred from Electronic Annotation more info
cytosol	ISS Inferred from Sequence or Structural Similarity more info
cytosol	TAS Traceable Author Statement more info
dendrite	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IEA Inferred from Electronic Annotation more info
perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
postsynaptic cytosol	IEA Inferred from Electronic Annotation more info
postsynaptic density	IEA Inferred from Electronic Annotation more info
presynaptic cytosol	IEA Inferred from Electronic Annotation more info
synaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein kinase C gamma type

NP_001303258.1

EC 2.7.11.13

NP_002730.1

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_009114.1 RefSeqGene

Range

5001..30435

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_669

mRNA and Protein(s)

NM_001316329.2 → NP_001303258.1 protein kinase C gamma type isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC008440, AK296434, AK312302, BC047876, DC318717

UniProtKB/Swiss-Prot

P05129

UniProtKB/TrEMBL

B2R5T1, B7Z3W6

Conserved Domains (4) summary

cd04026
Location:158 → 289

C2_PKC_alpha_gamma; C2 domain in Protein Kinase C (PKC) alpha and gamma

smart00220
Location:351 → 614

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05587
Location:354 → 677

STKc_cPKC; Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C

pfam00130
Location:101 → 153

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
NM_002739.5 → NP_002730.1 protein kinase C gamma type isoform 2

See identical proteins and their annotated locations for NP_002730.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AC008440, BC047876, DC318717

Consensus CDS

CCDS12867.1

UniProtKB/Swiss-Prot

P05129

Related

ENSP00000263431.3, ENST00000263431.4

Conserved Domains (4) summary

cd04026
Location:158 → 289

C2_PKC_alpha_gamma; C2 domain in Protein Kinase C (PKC) alpha and gamma

smart00220
Location:351 → 614

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05587
Location:354 → 677

STKc_cPKC; Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C

pfam00130
Location:101 → 153

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