InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKD2

Summary

InnateDB Protein

IDBP-382304.4

Last Modified

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

Gene Symbol

PRKD2

Protein Name

protein kinase D2

Synonyms

nPKC-D2; PKD2;

Species

Homo sapiens

Ensembl Protein

ENSP00000393978

InnateDB Gene

IDBG-58915 (PRKD2)

Protein Structure

UniProt Annotation

Function

Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress- induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. In response to oxidative stress, is phosphorylated at Tyr-438 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B. In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77. Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation. During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens. In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF- kappa-B-dependent pathway. During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane. Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis. In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, plays important roles in angiotensin-2- induced monocyte adhesion to endothelial cells. Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion. {ECO:0000269PubMed:14743217, ECO:0000269PubMed:15604256, ECO:0000269PubMed:16928771, ECO:0000269PubMed:17077180, ECO:0000269PubMed:17951978, ECO:0000269PubMed:17962809, ECO:0000269PubMed:18262756, ECO:0000269PubMed:19001381, ECO:0000269PubMed:19192391, ECO:0000269PubMed:23503467}.

Subcellular Localization

Cytoplasm. Cell membrane {ECO:0000250}. Nucleus. Golgi apparatus, trans-Golgi network. Note=Translocation to the cell membrane is required for kinase activation (By similarity). Accumulates in the nucleus upon CK1-mediated phosphorylation after activation of G-protein-coupled receptors. Nuclear accumulation is regulated by blocking nuclear export of active PRKD2 rather than by increasing import. {ECO:0000250}.

Disease Associations

Tissue Specificity

Widely expressed.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 52 experimentally validated interaction(s) in this database.

Experimentally validated
Total	52 [view]
Protein-Protein	52 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

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:0016772	transferase activity, transferring phosphorus-containing groups
GO:0046872	metal ion binding

Biological Process

GO:0001525	angiogenesis
GO:0001938	positive regulation of endothelial cell proliferation
GO:0006468	protein phosphorylation
GO:0007155	cell adhesion
GO:0008219	cell death
GO:0010595	positive regulation of endothelial cell migration
GO:0018105	peptidyl-serine phosphorylation
GO:0030949	positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0032743	positive regulation of interleukin-2 production
GO:0032757	positive regulation of interleukin-8 production
GO:0032793	positive regulation of CREB transcription factor activity
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0035556	intracellular signal transduction
GO:0035924	cellular response to vascular endothelial growth factor stimulus
GO:0038033	positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
GO:0043536	positive regulation of blood vessel endothelial cell migration
GO:0045743	positive regulation of fibroblast growth factor receptor signaling pathway
GO:0045766	positive regulation of angiogenesis
GO:0045785	positive regulation of cell adhesion
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046777	protein autophosphorylation
GO:0048010	vascular endothelial growth factor receptor signaling pathway
GO:0050852	T cell receptor signaling pathway
GO:0050862	positive regulation of T cell receptor signaling pathway
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0061154	endothelial tube morphogenesis
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:1901727	positive regulation of histone deacetylase activity
GO:1902533	positive regulation of intracellular signal transduction
GO:2000573	positive regulation of DNA biosynthetic process
GO:2001028	positive regulation of endothelial cell chemotaxis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001849 Pleckstrin homology 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
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00169
PF00130

PRINTS

PR00109
PR00008

PIRSF

SMART

SM00233
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt