InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCZ

Summary

InnateDB Protein

IDBP-227088.7

Last Modified

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

Gene Symbol

PRKCZ

Protein Name

protein kinase C, zeta

Synonyms

PKC-ZETA; PKC2;

Species

Homo sapiens

Ensembl Protein

ENSP00000383711

InnateDB Gene

IDBG-86108 (PRKCZ)

Protein Structure

UniProt Annotation

Function

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'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. 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. {ECO:0000269PubMed:11035106, ECO:0000269PubMed:12162751, ECO:0000269PubMed:15084291, ECO:0000269PubMed:15324659, ECO:0000269PubMed:18321849, ECO:0000269PubMed:9447975}.

Subcellular Localization

Cytoplasm. Endosome. Cell junction. Note=In the retina, localizes in the terminals of the rod bipolar cells (By similarity). Associates with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in brain, and to a lesser extent in lung, kidney and testis.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 171 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.

Experimentally validated
Total	171 [view]
Protein-Protein	170 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	22 [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:0008270	zinc ion binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0043560	insulin receptor substrate binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007596	blood coagulation
GO:0018105	peptidyl-serine phosphorylation
GO:0030010	establishment of cell polarity
GO:0030168	platelet activation
GO:0031333	negative regulation of protein complex assembly
GO:0032753	positive regulation of interleukin-4 production
GO:0045630	positive regulation of T-helper 2 cell differentiation
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0046628	positive regulation of insulin receptor signaling pathway
GO:0050732	negative regulation of peptidyl-tyrosine phosphorylation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0060291	long-term synaptic potentiation
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:2000463	positive regulation of excitatory postsynaptic membrane potential
GO:2000553	positive regulation of T-helper 2 cell cytokine production
GO:2000664	positive regulation of interleukin-5 secretion
GO:2000667	positive regulation of interleukin-13 secretion
GO:2001181	positive regulation of interleukin-10 secretion

Cellular Component

GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0016020	membrane
GO:0030054	cell junction
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR017892 Protein kinase, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00433

PRINTS

PR00109

PIRSF

SMART

SM00133
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt