Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PRKCI (P41743) - Overview - Molecular Target Synopsis

Protein


PRKCI, Protein kinase C iota type
Enzyme Classification 2.7.11.13
UniProt P41743

Also Known as KPCI_HUMAN, PRKCI, DXS1179E

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. Forms a complex with SQSTM1 and MP2K5 (By similarity). Interacts directly with SQSTM1 (Probable). Interacts with IKBKB. Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and a GTPase protein (CDC42 or RAC1). Part of a complex with LLGL1 and PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the ZN-finger domain, activates the kinase activity. Interacts with CDK7. Forms a complex with RAB2A and GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs). Interacts with ECT2 ('Thr-359' phosphorylated form). Interacts with VAMP2 (PubMed:17313651). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).

5LIH
STRUCTURE OF A PEPTIDE-SUBSTRATE BOUND TO PKCIOTA CORE KINASE DOMAIN
RCSB/PDB
Inspect Structure
See all 3D Structures for PRKCI

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
596ENSG00000163558ENST00000295797ENSP00000295797P41743-1

Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKCI has gain in 17 cell-lines, loss in 0 cell-lines and no signal in 987 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_3, T47D, NCI_H522

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: DV-90, NIH:OVCAR-3, OVSAHO

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, AG445, HMEC

(see details)

RNA Interference


PRKCI was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: G292, HELA. (see details)

3D Structures


For PRKCI there are:
9 structures (14 chains) solved
6 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKCI has been screened with 1701 compounds (2425 bioactivities), 262 compounds have bioactivities that show binding affinity of <= 500nM (281 bioactivities). (see details)