PRKCQ protein kinase C theta [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKCQprovided by HGNC
Official Full Name: protein kinase C thetaprovided by HGNC
Primary source: HGNC:HGNC:9410
See related: Ensembl:ENSG00000065675 MIM:600448; AllianceGenome:HGNC:9410
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PRKCT; nPKC-theta
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. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors. [provided by RefSeq, Jul 2008]
Expression: Broad expression in thyroid (RPKM 4.0), lymph node (RPKM 2.9) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10p15.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (6394097..6580646, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (6394273..6580768, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (6436059..6622608, complement)

Chromosome 10 - NC_000010.11 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?

PD1 inhibits PKCtheta;-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation.
Title: PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation.
The Peptidyl-Prolyl cis-trans isomerase, Pin1, associates with Protein Kinase C theta; via a critical Phospho-Thr-Pro motif in the V3 regulatory domain.
Title: The Peptidyl-Prolyl cis-trans isomerase, Pin1, associates with Protein Kinase C θ via a critical Phospho-Thr-Pro motif in the V3 regulatory domain.
Crocin attenuates NF-kappaB-mediated inflammation and proliferation in breast cancer cells by down-regulating PRKCQ.
Title: Crocin attenuates NF-κB-mediated inflammation and proliferation in breast cancer cells by down-regulating PRKCQ.
Crosstalk between miR-203 and PKCtheta regulates breast cancer stem cell markers.
Title: Crosstalk between miR-203 and PKCθ regulates breast cancer stem cell markers.
The Emerging Function of PKCtheta in Cancer.
Title: The Emerging Function of PKCtheta in Cancer.
PKCtheta-JunB axis via upregulation of VEGFR3 expression mediates hypoxia-induced pathological retinal neovascularization.
Title: PKCθ-JunB axis via upregulation of VEGFR3 expression mediates hypoxia-induced pathological retinal neovascularization.
Annexin A5 is essential for PKCtheta translocation during T-cell activation.
Title: Annexin A5 is essential for PKCθ translocation during T-cell activation.
PRKCQ inhibition enhances chemosensitivity of triple-negative breast cancer by regulating Bim.
Title: PRKCQ inhibition enhances chemosensitivity of triple-negative breast cancer by regulating Bim.
Two novel pleiotropic loci associated with osteoporosis and abdominal obesity.
Title: Two novel pleiotropic loci associated with osteoporosis and abdominal obesity.
These findings demonstrate that PKCtheta; plays an important role in a positive feedback regulatory loop that modulates TCR-proximal signaling and, moreover, provide a mechanistic explanation for earlier reports that documented an important role for PKCtheta; in T cell Ca(2+) signaling. This PKCtheta;-Zap70 interaction could potentially serve as a promising and highly selective immunosuppressive drug target in autoimmu...
Title: Phosphotyrosine-dependent interaction between the kinases PKCθ and Zap70 promotes proximal TCR signaling.

Submit: New GeneRIF Correction See all GeneRIFs (102)

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

EBI GWAS Catalog

Description
A genome-wide association study of bronchodilator response in asthmatics. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at CD40 and other loci confer risk of rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of antibody response to smallpox vaccine. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of body mass index in 23 000 individuals with and without asthma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. 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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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 micro domains 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	PKCtheta is a downstream effector of LCK and is recruited by HIV-1 Nef to form the Nef/LCK/PKCtheta complex, which promotes HIV transcription	PubMed
	nef	The formation of Nef/LCK/PKCtheta complex activates the ERK MAPK signaling pathway	PubMed
	nef	Interactions between HIV-1 Nef and PKC isozymes in Jurkat cells show that Nef interacts preferentially with PKCtheta; the interaction of Nef and PKCtheta is independent of calcium, but enhanced by phospholipid activators of PKC	PubMed
Tat	tat	HIV-1 Tat relocalizes PRKCQ (PKC-theta) and RELA (NFkB) to the nucleus of Jurkat T cells that stably express Tat	PubMed
	tat	HIV-1 Tat induces phosphorylation of Threonine538 in PRKCQ (PKC-theta) in Jurkat T cells stably expressing Tat	PubMed
	tat	HIV-1 Tat activates PRKCQ (PKC-theta) kinase activity, which leads to RELA (NFkB), NRAS, RAF1, MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK3 (ERK1), and MAPK1 (ERK2) activation, in Jurkat T cells that stably express Tat	PubMed
	tat	HIV-1 Tat upregulates PRKCQ (PKC-theta) expression in Jurkat T cells stably expressing Tat	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
	tat	Tat-triggered PKCdelta and PKCtheta activation results in the downstream signaling through the apoptosis pathways mediated by both ERK1/2 and caspase-3	PubMed
	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
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

SHGC-34074 (e-PCR)
- UniSTS:66575

SHGC-85682 (e-PCR)
- UniSTS:103725

STS-W72149 (e-PCR)
- UniSTS:76607

RH68983 (e-PCR)
- UniSTS:10356

D10S2139 (e-PCR)
- UniSTS:31654

PRKCQ_2384 (e-PCR)
- UniSTS:471728

STS-R16896 (e-PCR)
- UniSTS:9912

SHGC-36302 (e-PCR)
- UniSTS:31422

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	EXP Inferred from Experiment more info	PubMed
enables diacylglycerol-dependent serine/threonine kinase activity	TAS Traceable Author Statement more info
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 activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
involved_in axon guidance	TAS Traceable Author Statement more info
involved_in cell chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in membrane protein ectodomain proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T-helper 17 type immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T-helper 2 cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-17 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-2 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-4 production	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell growth	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of platelet aggregation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in aggresome	IDA Inferred from Direct Assay more info
located_in centriolar satellite	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in immunological synapse	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: protein kinase C theta type

NP_001229342.1

EC 2.7.11.13

NP_001269573.1

EC 2.7.11.13

NP_001269574.1

EC 2.7.11.13

NP_001310194.1

EC 2.7.11.13

NP_001310195.1

EC 2.7.11.13

NP_001310196.1

EC 2.7.11.13

NP_006248.1

EC 2.7.11.13

XP_005252553.1

EC 2.7.11.13

XP_005252554.1

EC 2.7.11.13

XP_054222269.1

EC 2.7.11.13

XP_054222270.1

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.

mRNA and Protein(s)

NM_001242413.2 → NP_001229342.1 protein kinase C theta type isoform 2

See identical proteins and their annotated locations for NP_001229342.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AA234440, AK293935, AK308099, AK312411, AY702977, BX647657, L01087, R40214

Consensus CDS

CCDS55701.1

UniProtKB/Swiss-Prot

Q04759

Related

ENSP00000380361.2, ENST00000397176.6

Conserved Domains (3) summary

PTZ00263
Location:376 → 631

PTZ00263; protein kinase A catalytic subunit; Provisional

pfam00130
Location:232 → 284

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

cl21453
Location:374 → 641

PKc_like; Protein Kinases, catalytic domain
NM_001282644.2 → NP_001269573.1 protein kinase C theta type isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 5' region. This difference results in translation initiation at an alternate AUG and results in an isoform (3) with a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AA234440, AK308099, BX647657, R40214

UniProtKB/Swiss-Prot

Q04759

Conserved Domains (3) summary

smart00220
Location:344 → 598

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05619
Location:338 → 668

STKc_nPKC_theta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta

pfam00130
Location:196 → 248

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
NM_001282645.1 → NP_001269574.1 protein kinase C theta type isoform 4

See identical proteins and their annotated locations for NP_001269574.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks an exon in the 5' region. This difference results in translation initiation at an alternate AUG and results in an isoform (4) with a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AA234440, AK293935, AK308099, BX647657, L01087, R40214

Consensus CDS

CCDS60482.1

UniProtKB/Swiss-Prot

Q04759

Related

ENSP00000441752.1, ENST00000539722.5

Conserved Domains (2) summary

cd05619
Location:249 → 579

STKc_nPKC_theta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta

pfam00130
Location:107 → 159

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
NM_001323265.1 → NP_001310194.1 protein kinase C theta type isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (5) and variant 1 both encode isoform 1.

Source sequence(s)

AL137145, AL158043

Consensus CDS

CCDS7079.1

UniProtKB/Swiss-Prot

B4DF52, Q04759, Q14DH6, Q3MJF1, Q64FY5, Q9H508, Q9H549

Conserved Domains (2) summary

cd05619
Location:374 → 704

STKc_nPKC_theta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta

pfam00130
Location:232 → 284

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
NM_001323266.2 → NP_001310195.1 protein kinase C theta type isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (6) and variant 4 both encode isoform 4.

Source sequence(s)

AL137145, AL158043

Consensus CDS

CCDS60482.1

UniProtKB/Swiss-Prot

Q04759

Conserved Domains (2) summary

cd05619
Location:249 → 579

STKc_nPKC_theta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta

pfam00130
Location:107 → 159

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
NM_001323267.2 → NP_001310196.1 protein kinase C theta type isoform 5

Status: VALIDATED

Source sequence(s)

AL137145, AL158043
NM_006257.5 → NP_006248.1 protein kinase C theta type isoform 1

See identical proteins and their annotated locations for NP_006248.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1 and 5 both encode the same isoform (1).

Source sequence(s)

AA234440, AK293935, AK308099, AK312411, BX647657, R40214

Consensus CDS

CCDS7079.1

UniProtKB/Swiss-Prot

B4DF52, Q04759, Q14DH6, Q3MJF1, Q64FY5, Q9H508, Q9H549

Related

ENSP00000263125.5, ENST00000263125.10

Conserved Domains (2) summary

cd05619
Location:374 → 704

STKc_nPKC_theta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta

pfam00130
Location:232 → 284

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_000010.11 Reference GRCh38.p14 Primary Assembly

Range

6394097..6580646 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005252497.5 → XP_005252554.1 protein kinase C theta type isoform X2

Conserved Domains (3) summary

smart00220
Location:414 → 668

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam00130
Location:266 → 318

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

cl21453
Location:408 → 695

PKc_like; Protein Kinases, catalytic domain
XM_005252496.5 → XP_005252553.1 protein kinase C theta type isoform X1

Conserved Domains (3) summary

smart00220
Location:414 → 668

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05619
Location:408 → 738

STKc_nPKC_theta; Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta

pfam00130
Location:266 → 318

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