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Details on Person UniProt:Q9BZL6 PRKD2

Class:IdReferenceGeneProduct:58215
_chainChangeLogchain:1-878 added on Sat February 7 2015
_displayNameUniProt:Q9BZL6 PRKD2
_timestamp2025-02-21 18:38:10
chainchain:1-878
checksum8BAB45E8F99D23E7
commentFUNCTION 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:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, 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).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR Activated by DAG and phorbol esters (PubMed:12058027, PubMed:17962809, PubMed:28428613). Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes (PubMed:17962809). Autophosphorylation of Ser-710 and phosphorylation of Ser-706 by PKC relieves auto-inhibition by the PH domain (PubMed:17962809). Catalytic activity is further increased by phosphorylation at Tyr-717 in response to oxidative stress (PubMed:28428613).SUBUNIT 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).INTERACTION Translocation to the cell membrane is required for kinase activation. 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.ALTERNATIVE PRODUCTS Widely expressed.PTM Phosphorylation of Ser-876 correlates with the activation status of the kinase (PubMed:11062248). Ser-706 or/and Ser-710 are probably phosphorylated by PKC (PubMed:12058027, PubMed:28428613). Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting (PubMed:17962809). Phosphorylation at Ser-244, Ser-706 and Ser-710 is required for nuclear localization (PubMed:17962809). Phosphorylated at Tyr-438 by ABL1 in response to oxidative stress (PubMed:15604256). Phosphorylated at Tyr-717 by ABL1 specifically in response to oxidative stress; requires prior phosphorylation at Ser-706 or/and Ser-710 (PubMed:28428613).SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.
descriptionrecommendedName: Serine/threonine-protein kinase D2 ecNumber evidence="9 10 17 23"2.7.11.13 alternativeName: nPKC-D2
geneNamePRKD2
PKD2
HSPC187
identifierQ9BZL6
isSequenceChangedFALSE
keyword3D-structure
Adaptive immunity
Alternative splicing
Angiogenesis
ATP-binding
Cell adhesion
Cell membrane
Cytoplasm
Golgi apparatus
Immunity
Kinase
Magnesium
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
namePRKD2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8962293] ENSEMBL:ENSG00000105287 PRKD2 [Homo sapiens]
secondaryIdentifierKPCD2_HUMAN
B4DTS2
M0QZW1
M0R2R2
Q8NCK8
Q8TB08
Q9P0T6
Q9Y3X8
sequenceLength878
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8974335] UniProt:Q9BZL6-1 PRKD2 [Homo sapiens]
[ReferenceIsoform:8974336] UniProt:Q9BZL6-2 PRKD2 [Homo sapiens]
[ReferenceIsoform:9607537] UniProt:Q9BZL6-3 PRKD2 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:58214] PRKD2 [cytosol] [Homo sapiens]
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