Tchem PRKCI Protein kinase C iota type

Protein Summary

Description

Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P41743
• D3DNQ4
• Q8WW06

Gene Name

• PRKCI

Ensembl ID

• ENST00000295797
• ENSP00000295797
• ENSG00000163558

Symbol

• DXS1179E
• PKCI
• DXS1179E
• nPKC-iota

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
biological process	0.99
interacting protein	0.99
molecular function	0.97
virus perturbation	0.94

Protein Classes

PANTHER Classes

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

Protein / Transfer/carrier Protein / Protein Kinase C Iota Type

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

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

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Pkc Family / Pkc Iota Subfamily / Protein Kinase C Iota 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: 120.96   (req: < 5)

Gene RIFs: 98   (req: <= 3)

Antibodies: 203   (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: 120.96   (req: >= 5)

Gene RIFs: 98   (req: > 3)

Antibodies: 203   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 36

Tchem

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

Active Ligands: 7

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 (7)

Explore Active Ligands

1 – 7 of 7

staurosporine

PRKCITchem Kinase

pKd : 7.89

SID103904960

PRKCITchem Kinase

pKi : 8.5

CHEMBL4212424

PRKCITchem Kinase

pIC50 : 8.57

CHEMBL4202753

PRKCITchem Kinase

pIC50 : 8.55

CHEMBL4208685

PRKCITchem Kinase

pIC50 : 8.42

CHEMBL4206065

PRKCITchem Kinase

pIC50 : 8.3

CHEMBL4216507

PRKCITchem Kinase

pIC50 : 8.19

Protein-Protein Interactions (182)

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1 – 10 of 182

• See Interactions on String-DB

PARD6B

Tbio

Novelty:  0.08495161

p_int:  0.999999983

p_ni:  1.7e-8

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

PRKCZ

Tchem

Family:  Kinase

Novelty:  0.00201366

p_int:  0.999997945

p_ni:  0.000002055

Score:  0.975

Data Source:  BioPlex,STRINGDB

LLGL2

Tbio

Novelty:  0.07084531

p_int:  0.999967739

p_ni:  0.000032261

Score:  0.993

Data Source:  BioPlex,STRINGDB

GREM2

Tbio

Novelty:  0.01839564

p_int:  0.997729002

p_ni:  0.002270998

Data Source:  BioPlex

IL17F

Tbio

Novelty:  0.00223549

p_int:  0.997190479

p_ni:  0.00280952

p_wrong:  1e-9

Data Source:  BioPlex

FYN

Tclin

Family:  Kinase

Novelty:  0.00072167

p_int:  0.995916269

p_ni:  0.004083729

p_wrong:  1e-9

Score:  0.207

Data Source:  BioPlex,STRINGDB

EDDM3B

Tdark

Novelty:  0.12874735

p_int:  0.99570024

p_ni:  0.00429976

Data Source:  BioPlex

NGEF

Tbio

Novelty:  0.04628547

p_int:  0.991970848

p_ni:  0.008028852

p_wrong:  3e-7

Score:  0.244

Data Source:  BioPlex,STRINGDB

KBTBD7

Tdark

Novelty:  0.4947466

p_int:  0.991736467

p_ni:  0.00826352

p_wrong:  1.3e-8

Data Source:  BioPlex

GPR156

Tdark

Family:  GPCR

Novelty:  0.39183023

p_int:  0.991279307

p_ni:  0.008720593

p_wrong:  1.01e-7

Data Source:  BioPlex

Nearest Tclin Targets (4)

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Upstream (2)

Downstream (2)

1 – 2 of 2

PIK3CA

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  4

1: Platelet activation

2: Rap1 signaling pathway

3: Human papillomavirus infection

4: Insulin signaling pathway

PIK3CD

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  4

1: Platelet activation

2: Rap1 signaling pathway

3: Human papillomavirus infection

4: Insulin signaling pathway

Pathways (57)

Reactome (12)

KEGG (7)

PathwayCommons (29)

WikiPathways (9)

Cell junction organization (R-HSA-446728)

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5

1 – 5 of 12

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cell junction organization	88 targets	R-HSA-446728
Reactome	Cell-Cell communication	121 targets	R-HSA-1500931
Reactome	Cell-cell junction organization	63 targets	R-HSA-421270
Reactome	Death Receptor Signalling	141 targets	R-HSA-73887
Reactome	Pre-NOTCH Expression and Processing	78 targets	R-HSA-1912422

Name	Explore in Pharos	Explore in Source
Cell junction organization	88 targets	R-HSA-446728
Cell-Cell communication	121 targets	R-HSA-1500931
Cell-cell junction organization	63 targets	R-HSA-421270
Death Receptor Signalling	141 targets	R-HSA-73887
Pre-NOTCH Expression and Processing	78 targets	R-HSA-1912422

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (52)

Functions (7)

Components (16)

Processes (29)

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1 – 7 of 7

GO Term	Evidence	Assigned by
phospholipid binding	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase C activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
ATP binding	Traceable Author Statement (TAS)	UniProtKB
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein domain specific binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (7)

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1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
prostate carcinoma	EFO_0001663	4	2	0	1.2	76.9
glomerular filtration rate	EFO_0005208	3	2	3		31.3
creatinine measurement	EFO_0004518	2	1	2		17.8
urinary albumin to creatinine ratio	EFO_0007778	3	1	3		14.1
albuminuria	EFO_0004285	1	1	1		12.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
prostate carcinoma	EFO_0001663	0	1.2	76.9
glomerular filtration rate	EFO_0005208	3		31.3
creatinine measurement	EFO_0004518	2		17.8
urinary albumin to creatinine ratio	EFO_0007778	3		14.1
albuminuria	EFO_0004285	1		12.6

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
ATP-binding
Complete proteome
Cytoplasm
Endosome
Kinase
Membrane
Metal-binding
Nucleotide-binding

GWAS Trait Find Similar Targets

No Header	No Header
albuminuria
aspartate aminotransferase measurement
creatinine measurement
glomerular filtration rate
Moderate albuminuria
prostate carcinoma
urinary albumin to creatinine ratio

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	protein kinase C iota	VGNC:12133	450143
Mouse	protein kinase C, iota	MGI:99260	18759
Rat	protein kinase C, iota	RGD:620961	84006
Dog	protein kinase C iota	VGNC:44982	478686
Horse	protein kinase C iota	VGNC:21847	100063737

Species	Name	OMA	EggNOG	Inparanoid
Chimp	protein kinase C iota
Mouse	protein kinase C, iota
Rat	protein kinase C, iota
Dog	protein kinase C iota
Horse	protein kinase C iota

Publication Statistics

PubMed Score 120.96

PubMed score by year

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PubTator Score 49.63

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Related Publications

Text Mined References (154)

GeneRif Annotations (98)

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PMID	Year	Title