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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

PRKD2 Gene

protein-coding GIFtS: 64
GCID: GC19M047177

protein kinase D2

Explore 13 diseases affiliated with
PRKD2 via

MalaCards

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Protein Kinase D2¹ ²		DKFZP586E0820¹
PKD2¹ ² ³ ⁵		HSPC187¹
NPKC-D2¹		Serine/Threonine-Protein Kinase D2²
EC 2.7.11.13³ ⁸		EC 2.7.11⁸

External Ids:	HGNC: 17293¹	Entrez Gene: 25865²	Ensembl: ENSG00000105287⁷	OMIM: 607074⁵	UniProtKB: Q9BZL6³

Export aliases for PRKD2 gene to outside databases

Previous GC identifers: GC19M047568 GC19M051853 GC19M051869 GC19M043602

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for PRKD2:

The protein encoded by this gene belongs to the protein kinase D (PKD) family of serine/threonine protein kinases. This

kinase can be activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric

cancer cells. It can bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral

membrane protein exit from TGN. Alternative splicing results in multiple transcript variants encoding different

isoforms. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: KPCD2_HUMAN, Q9BZL6

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

summary for PRKD2:

The protein kinase D (PKD) family of serine/threonine protein kinases contains three members; PKD1, PKD2 and

PKD2. These enzymes occupy a unique position in the signal transduction pathway initiated by diacylglycerol

(DAG) and protein kinase C (PKC). PKDs are direct targets of DAG, and also lie downstream of PKC in a novel

signal transduction pathway that is implicated in a variety of biological processes. Structurally, PKDs

contain an N' terminal cysteine-rich domain (CRD), which binds phorbol esters with high affinity and has a

role in mediating PKD translocation to the plasma membrane upon activation. The PH domains have an

autoregulatory phosphorylation site (PKD1 and PKD2 only) and the catalytic domains have a high degree of

homology to myosin light chain and calmodulin-dependent kinases. In the inactivated state, PKD1 and PKD2 are

localized mainly to the cytoplasm, whilst PKD3 is found both in the cytoplasm and nucleus. Kinase activity

of these enzymes is repressed by their CRD and PH domains. PKDs are activated by a variety of stimuli

including regulatory peptides, lysophosphatidic acid, thrombin, PDGF, IGF-1, oxidative stress,

cholecystokinin, Gbetagamma, ATP and more. These stimuli produce a rapid generation of DAG, which induces

CRD-mediated PKD translocation from the cytosol to the plasma membrane. Novel PKCs are also recruited to the

plasma membrane in response to DAG generation. Novel PKCs are allosterically activated by DAG, and

transphosphorylate PKDs. This stabilizes PKD in its active conformation. Activated PKD dissociates from the

plasma membrane, translocates to the cytosol and subsequently to the nucleus. PKDs have been implicated in

fundamental physiological processes including signal transduction, membrane trafficking, and cell survival,

migration, differentiation and proliferation. PKD upregulates the ERK and Ras signaling pathways, and

suppresses the JNK signaling pathway. These enzymes regulate the budding of secretory vesicles from the

trans-Golgi network and promote integrin recruitment to focal adhesions. In addition, PKDs have a role in

regulating apoptosis and have functions in cell survival pathways induced by oxidative stress. They also

have a role in immune regulation. Despite the plethora of physiological processes PKDs are involved in, only

a few direct targets are known. These include kidins220, an integral membrane protein of neuroendocrine

cells, c-Jun and RIN1, a protein that associates with Ras and 14.3.3 and activates the Ras-MEK-ERK pathway.

Gene Wiki entry for PRKD2

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011109.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the PRKD2 gene promoter:
AREB6 Spz1 Roaz c-Ets-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): PRKD2 promoter sequence

Search SABiosciences Chromatin IP Primers for PRKD2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat PRKD2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19q13.3 Ensembl cytogenetic band: 19q13.32 HGNC cytogenetic band: 19q13.2

PRKD2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PRKD2 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19M047177: view genomic region (about GC identifiers)

Start:	47,177,573 bp from pter	End:	47,220,384 bp from pter
Size:	42,812 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: KPCD2_HUMAN, Q9BZL6 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase D2

Size: 878 amino acids; 96750 Da

Cofactor: Magnesium (By similarity)

Subunit: Interacts (via C-terminus) with LCK

Subcellular location: Cytoplasm. Cell membrane (By similarity). 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

Sequence caution: Sequence=AAF36107.1; Type=Frameshift; Positions=604, 606, 738, 744, 755, 758, 833, 854;

2 PDB 3D structures from and Proteopedia for PRKD2:

2COA (3D)

3BGM (3D)

Secondary accessions: Q8TB08 Q9P0T6 Q9Y3X8

Explore the universe of human proteins at neXtProt for PRKD2: NX_Q9BZL6

Post-translational modifications:

Phosphorylation of Ser-876 correlates with the activation status of the kinase. Ser-706 is probably phosphorylated by

PKC. Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting.

Phosphorylation at Ser-244, Ser-706 and Ser-710 is required for nuclear localization. Phosphorylated at Tyr-438 by

ABL1 in response to oxidative stress¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q9BZL6

4/30 DME Specific Peptides for PRKD2 (Q9BZL6) (see all 30)

IPNNCSG

VKVPHTF

LSHPWLQ

HSYTRPT

PRKD2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (4 alternative transcripts):

NP_001073349.1 NP_001073350.1 NP_001073351.1 NP_057541.2

ENSEMBL proteins:

ENSP00000291281 ENSP00000393978

Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant PRKD2 Protein
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for PRKD2
	OriGene Purified Proteins (see all 2): PRKD2 OriGene Protein Over-expression Lysate (see all 5): PRKD2 OriGene Custom Protein Services for PRKD2
	GenScript Custom Purified and Recombinant Proteins Services for PRKD2
	Novus Biologicals PRKD2 Proteins Novus Biologicals PRKD2 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for PRKD2

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	NAS	--
GO:0005634	nucleus	IDA	17077180
GO:0005737	cytoplasm	IDA	17077180
GO:0005794	Golgi apparatus	IEA	--
GO:0005886	plasma membrane	IEA	--

PRKD2 for ontologies About GeneDecksing

PRKD2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of PRKD2
	Browse R&D Systems for Antibodies
	Cell Signaling Technology (CST) Antibodies for PRKD2 (PKD2)
	OriGene Antibodies (see all 10): PRKD2 OriGene Custom Antibody Services for PRKD2
	GenScript Custom Superior Antibodies Services for PRKD2
	Novus Biologicals PRKD2 Antibodies
	Abcam antibodies for PRKD2
	Uscn Antibodies for PRKD2
	ThermoFisher Antibody for PRKD2

Assay Products for PRKD2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for PRKD2
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for PRKD2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

PRKD2 for domains About GeneDecksing

5/10 InterPro domains/families (see all 10):

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR020454 DAG/PE-bd

IPR011009 Kinase-like_dom

IPR001849 Pleckstrin_homology

Graphical View of Domain Structure for InterPro Entry Q9BZL6

ProtoNet protein and cluster: Q9BZL6

1 Blocks protein family: IPB001849 Pleckstrin-like

UniProtKB/Swiss-Prot: KPCD2_HUMAN, Q9BZL6

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily

Similarity: Contains 1 PH domain

Similarity: Contains 2 phorbol-ester/DAG-type zinc fingers

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: