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

PRKD2 (Q9BZL6) - Overview - Molecular Target Synopsis

Protein


PRKD2, Serine/threonine-protein kinase D2
Enzyme Classification 2.7.11.13
UniProt Q9BZL6

Also Known as KPCD2_HUMAN, PRKD2, PKD2

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 (PubMed:15604256, PubMed:14743217, PubMed:17077180, PubMed:16928771, PubMed:17962809, PubMed:17951978, PubMed:18262756, PubMed:19192391, PubMed:19001381, PubMed:23503467, PubMed:28428613). 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 (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). 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 (PubMed:17962809). 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 (PubMed:17077180). 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 (By similarity). 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 (PubMed:16928771). 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 (PubMed:19192391). 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 (PubMed:14743217). 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 (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). 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 (PubMed:23503467). Interacts (via C-terminus) with LCK (PubMed:19192391). Interacts (via N-terminal AP-rich region) with CIB1 isoform 2 (PubMed:23503467). Interacts (via N-terminus and zing-finger domain 1 and 2) with PRKCD in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation (PubMed:28428613).

4NNX
8 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE D2
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF PKD2 PHOSPHOPEPTIDE BOUND TO HLA-A2
RCSB/PDB
Inspect Structure
See all 3D Structures for PRKD2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PRKD2 is active in the following subcellular-locations: cell membrane, cytoplasm, golgi apparatus, nucleus, trans-golgi network.
GO terms: PRKD2 is active in the following subcellular-locations: cytoplasm, cytosol, Golgi apparatus, nucleoplasm, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKD2 has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HT29, CCRF_CEM, K_562

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KMM-1, KARPAS-620, NCI-H929

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: SK-N-SH, HUVEC, A549

(see details)

RNA Interference


PRKD2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MIAPACA2, JIMT1. (see details)

3D Structures


For PRKD2 there are:
4 structures (4 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKD2 has been screened with 955 compounds (1565 bioactivities), 42 compounds have bioactivities that show binding affinity of <= 500nM (48 bioactivities). (see details)