Tchem PRKCZ Protein kinase C zeta type

Protein Summary

Description

Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro (PubMed:17313651). Isoform 2: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance. Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q05513
• A8K4N0
• A8MU64
• B7Z2J7
• E9PCW2
• Q15207
• Q5SYT5
• Q969S4

Gene Name

• PRKCZ

Ensembl ID

• ENST00000378567
• ENSP00000367830
• ENSG00000067606
• ENST00000400921
• ENSP00000383712
• ENST00000461106
• ENSP00000426412

Symbol

• PKC2
• PKC2
• PKC-ZETA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
protein domain	1
molecular function	0.99
biological term	0.98

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Protein Kinase C Zeta Type

Protein / Transfer/carrier Protein / Protein Kinase C Zeta Type

Protein / Calcium-binding Protein / Intracellular Calcium-sensing Protein / Calmodulin / Protein Kinase C Zeta Type

Protein / Calcium-binding Protein / Annexin / Protein Kinase C Zeta Type

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Pkc Family / Pkc Iota Subfamily / Protein Kinase C Zeta Type

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 501.3   (req: < 5)

Gene RIFs: 166   (req: <= 3)

Antibodies: 774   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 501.3   (req: >= 5)

Gene RIFs: 166   (req: > 3)

Antibodies: 774   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 50

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 36

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (36)

Explore Active Ligands

1 – 10 of 36

balanol

PRKCZTchem Kinase

pKd : 8.8

SID103904203

PRKCZTchem Kinase

pKi : 8.2

SID103904960

PRKCZTchem Kinase

pKi : 8.5

GSK269962A

PRKCZTchem Kinase

pKi : 7.6

G&ouml; 6983

PRKCZTchem Kinase

pIC50 : 8.22

CHEMBL514197

PRKCZTchem Kinase

pIC50 : 8.65

CHEMBL473631

PRKCZTchem Kinase

pIC50 : 8.25

CHEMBL2393431

PRKCZTchem Kinase

pEC50 : 9

4-(5-(Piperidin-3-ylamino)isoquinolin-7-yl)phenol

PRKCZTchem Kinase

pIC50 : 9.22

CHEMBL4635482

PRKCZTchem Kinase

pIC50 : 10

Protein-Protein Interactions (259)

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1 – 10 of 259

• See Interactions on String-DB

PARD6B

Tbio

Novelty:  0.08495161

p_int:  1

Score:  0.995

Data Source:  BioPlex,STRINGDB

LLGL2

Tbio

Novelty:  0.07084531

p_int:  0.999999997

p_ni:  3e-9

Score:  0.86

Data Source:  BioPlex,STRINGDB

PRKCI

Tchem

Family:  Kinase

Novelty:  0.0076377

p_int:  0.999997945

p_ni:  0.000002055

Score:  0.975

Data Source:  BioPlex,STRINGDB

PARD6G

Tbio

Novelty:  0.23553331

p_int:  0.999656778

p_ni:  1.3e-8

p_wrong:  0.000343209

Score:  0.996

Data Source:  BioPlex,STRINGDB

LLGL1

Tbio

Novelty:  0.01591552

p_int:  0.999421931

p_ni:  0.000578069

Score:  0.922

Data Source:  BioPlex,STRINGDB

TRIM41

Tbio

Family:  Enzyme

Novelty:  0.17238173

p_int:  0.999245634

p_ni:  0.000754365

p_wrong:  1e-9

Score:  0.329

Data Source:  BioPlex,STRINGDB

WWC1

Tbio

Novelty:  0.00905646

p_int:  0.997932395

p_ni:  0.000026397

p_wrong:  0.002041208

Score:  0.979

Data Source:  BioPlex,STRINGDB

NIPSNAP2

Tbio

Novelty:  0.0908929

p_int:  0.990044862

p_ni:  0.009955138

Score:  0.219

Data Source:  BioPlex,STRINGDB

CDC42BPB

Tchem

Family:  Kinase

Novelty:  0.12012285

p_int:  0.986977157

p_ni:  0.013022843

Score:  0.21

Data Source:  BioPlex,STRINGDB

SQSTM1

Tbio

Novelty:  0.00100555

p_int:  0.971148548

p_ni:  0.028851452

Score:  0.955

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (5)

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Upstream (2)

Downstream (3)

1 – 2 of 2

PIK3CD

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  12

1: Axon guidance

2: Platelet activation

3: Relaxin signaling pathway

4: Type II diabetes mellitus

more:  8 more common pathways

PIK3CA

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  12

1: Axon guidance

2: Platelet activation

3: Relaxin signaling pathway

4: Type II diabetes mellitus

more:  8 more common pathways

Pathways (100)

Reactome (18)

KEGG (15)

PathwayCommons (47)

WikiPathways (20)

ESR-mediated signaling (R-HSA-8939211)

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1 – 5 of 18

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	ESR-mediated signaling	189 targets	R-HSA-8939211
Reactome	Estrogen-stimulated signaling through PRKCZ	6 targets	R-HSA-9634635
Reactome	Extra-nuclear estrogen signaling	74 targets	R-HSA-9009391
Reactome	GPVI-mediated activation cascade	32 targets	R-HSA-114604
Reactome	Hemostasis	666 targets	R-HSA-109582

Name	Explore in Pharos	Explore in Source
ESR-mediated signaling	189 targets	R-HSA-8939211
Estrogen-stimulated signaling through PRKCZ	6 targets	R-HSA-9634635
Extra-nuclear estrogen signaling	74 targets	R-HSA-9009391
GPVI-mediated activation cascade	32 targets	R-HSA-114604
Hemostasis	666 targets	R-HSA-109582

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (75)

Functions (11)

Components (25)

Processes (39)

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10

1 – 10 of 11

GO Term	Evidence	Assigned by
protein kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	BHF-UCL
protein kinase C activity	Traceable Author Statement (TAS)	Reactome
insulin receptor substrate binding	Inferred by Curator (IC)	BHF-UCL
14-3-3 protein binding	Inferred from Electronic Annotation (IEA)	Ensembl
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
phospholipase binding	Inferred from Electronic Annotation (IEA)	Ensembl
potassium channel regulator activity	Inferred from Electronic Annotation (IEA)	Ensembl
protein domain specific binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (18)

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1 – 5 of 18

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet count	EFO_0004309	2	2	2		83.7
platelet crit	EFO_0007985	2	2	2		80.4
serum alanine aminotransferase measurement	EFO_0004735	2	2	1	6	76.2
electrocardiography	EFO_0004327	1	1	88		68.6
low density lipoprotein cholesterol measurement	EFO_0004611	1	1	1		52.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 18

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet count	EFO_0004309	2		83.7
platelet crit	EFO_0007985	2		80.4
serum alanine aminotransferase measurement	EFO_0004735	1	6	76.2
electrocardiography	EFO_0004327	88		68.6
low density lipoprotein cholesterol measurement	EFO_0004611	1		52.4

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UniProt Keyword Find Similar Targets

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Alternative promoter usage
Alternative splicing
ATP-binding
Cell junction
Complete proteome
Cytoplasm
Endosome
Inflammatory response
Kinase
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
body height
electrocardiography
influenza A (H1N1)
low density lipoprotein cholesterol measurement
mean corpuscular volume
physical activity measurement
platelet count
platelet crit
PR interval
red blood cell distribution width

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
pigmentation phenotype
vision/eye phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	protein kinase C zeta type-like		100430236
Mouse	protein kinase C, zeta	MGI:97602	18762
Rat	protein kinase C, zeta	RGD:3399	25522
Dog	protein kinase C zeta	VGNC:44985	479577
Horse	protein kinase C zeta	VGNC:21850	100064240

Species	Name	OMA	EggNOG	Inparanoid
Macaque	protein kinase C zeta type-like
Mouse	protein kinase C, zeta
Rat	protein kinase C, zeta
Dog	protein kinase C zeta
Horse	protein kinase C zeta

Publication Statistics

PubMed Score 501.30

PubMed score by year

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PubTator Score 353.40

PubTator score by year

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Patents

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Related Publications

Text Mined References (287)

GeneRif Annotations (166)

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PMID	Year	Title