InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCI

Summary

InnateDB Protein

IDBP-64430.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKCI

Protein Name

protein kinase C, iota

Synonyms

DXS1179E; nPKC-iota; PKCI;

Species

Homo sapiens

Ensembl Protein

ENSP00000295797

InnateDB Gene

IDBG-64428 (PRKCI)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:10356400, ECO:0000269PubMed:10467349, ECO:0000269PubMed:10906326, ECO:0000269PubMed:11042363, ECO:0000269PubMed:11724794, ECO:0000269PubMed:12871960, ECO:0000269PubMed:14684752, ECO:0000269PubMed:15994303, ECO:0000269PubMed:18270268, ECO:0000269PubMed:19327373, ECO:0000269PubMed:21189248, ECO:0000269PubMed:21419810, ECO:0000269PubMed:8226978, ECO:0000269PubMed:9346882}.

Subcellular Localization

Cytoplasm. Membrane. Endosome. Nucleus. Note=Transported into the endosome through interaction with SQSTM1/p62. After phosphorylation by SRC, transported into the nucleus through interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and nucleus. Transported to vesicular tubular clusters (VTCs) through interaction with RAB2A.

Disease Associations

Tissue Specificity

Predominantly expressed in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. Highly expressed in non-small cell lung cancers. {ECO:0000269PubMed:15994303, ECO:0000269PubMed:7607695, ECO:0000269PubMed:8226978}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 100 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	100 [view]
Protein-Protein	98 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004697	protein kinase C activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0005543	phospholipid binding
GO:0008270	zinc ion binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019904	protein domain specific binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006612	protein targeting to membrane
GO:0007010	cytoskeleton organization
GO:0007015	actin filament organization
GO:0010976	positive regulation of neuron projection development
GO:0016192	vesicle-mediated transport
GO:0016477	cell migration
GO:0032869	cellular response to insulin stimulus
GO:0034329	cell junction assembly
GO:0034351	negative regulation of glial cell apoptotic process
GO:0034613	cellular protein localization
GO:0035089	establishment of apical/basal cell polarity
GO:0035556	intracellular signal transduction
GO:0042462	eye photoreceptor cell development
GO:0043066	negative regulation of apoptotic process
GO:0043434	response to peptide hormone
GO:0043524	negative regulation of neuron apoptotic process
GO:0045197	establishment or maintenance of epithelial cell apical/basal polarity
GO:0045216	cell-cell junction organization
GO:0046326	positive regulation of glucose import
GO:0046903	secretion
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048194	Golgi vesicle budding
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0060252	positive regulation of glial cell proliferation
GO:0061024	membrane organization
GO:0070555	response to interleukin-1
GO:0070830	tight junction assembly
GO:0090004	positive regulation of establishment of protein localization to plasma membrane
GO:2000353	positive regulation of endothelial cell apoptotic process

Cellular Component

GO:0000133	polarisome
GO:0000139	Golgi membrane
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005923	tight junction
GO:0015630	microtubule cytoskeleton
GO:0016324	apical plasma membrane
GO:0031252	cell leading edge
GO:0043220	Schmidt-Lanterman incisure
GO:0043234	protein complex
GO:0045171	intercellular bridge
GO:0045177	apical part of cell
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000270 Phox/Bem1p
IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR012233 Protein kinase C, zeta/iota
IPR017892 Protein kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00564
PF00069
PF07714
PF00130
PF00433

PRINTS

PR00109
PR00008

PIRSF

PIRSF000554

SMART

SM00666
SM00133
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References