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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

PRKD1 Gene

protein-coding GIFtS: 64
GCID: GC14M030045

protein kinase D1

(Previous names: protein kinase C, mu )
(Previous symbol: PRKCM)

Explore 26 diseases affiliated with
PRKD1 via

MalaCards

our new
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 D1¹ ²		NPKC-Mu¹
PKD¹ ² ³ ⁵		EC 2.7.11.13³ ⁸
PRKCM¹ ² ³ ⁵		PKC-Mu¹
PKCM¹ ²		PKC-MU²
Protein Kinase C, Mu¹ ²		Serine/Threonine-Protein Kinase D1²
Protein Kinase C Mu Type² ³		PKD1³
Protein Kinase D² ³		EC 2.7.11⁸
NPKC-D1¹

External Ids:	HGNC: 9407¹	Entrez Gene: 5587²	Ensembl: ENSG00000184304⁷	OMIM: 605435⁵	UniProtKB: Q15139³

Export aliases for PRKD1 gene to outside databases

Previous GC identifers: GC14M029115 GC14M010161

(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 PRKD1:

PRKD1 is a serine/threonine kinase that regulates a variety of cellular functions, including membrane receptor

signaling, transport at the Golgi, protection from oxidative stress at the mitochondria, gene transcription, and

regulation of cell shape, motility, and adhesion (summary by Eiseler et al., 2009 (PubMed 19329994)).(supplied by

OMIM, Nov 2010)

UniProtKB/Swiss-Prot: KPCD1_HUMAN, Q15139

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 MAPK8/JNK1 and Ras signaling, Golgi

membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation

by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac

hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response.

Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression

of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates

RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding

to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein

beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein

transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles

that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase

beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential

production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of

specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and

contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1.

Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly

forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenic protein 2 (BMP2)-induced nuclear

export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an

important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in

the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced

by the neuropeptide bombesin or vasopressin 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.

Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained

activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by

phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional

activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac

remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament

calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in

angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In

response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and

endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1

is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells

to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated

inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production

of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be

involved in pain transmission by directly modulating TRPV1 receptor

summary for PRKD1:

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 PRKD1 (Protein kinase D1)

(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_000014.8 NC_018925.1 NT_026437.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the PRKD1 gene promoter:
CREB AP-1 ATF-2 deltaCREB c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): PRKD1 promoter sequence

Search SABiosciences Chromatin IP Primers for PRKD1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat PRKD1

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

Entrez Gene cytogenetic band: 14q11 Ensembl cytogenetic band: 14q12 HGNC cytogenetic band: 14q11

PRKD1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PRKD1 gene location

GeneLoc information about chromosome 14 GeneLoc Exon Structure

GeneLoc location for GC14M030045: view genomic region (about GC identifiers)

Start:	30,045,685 bp from pter	End:	30,661,104 bp from pter
Size:	615,420 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: KPCD1_HUMAN, Q15139 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase D1

Size: 912 amino acids; 101704 Da

Cofactor: Magnesium

Subunit: Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with MAPK13 and SRC. Interacts with DAPK1 in an

oxidative stress-regulated manner

Subcellular location: Cytoplasm. Cell membrane. Golgi apparatus, trans-Golgi network (By similarity).

Note=Translocation to the cell membrane is required for kinase activation

Secondary accessions: A6NL64 B2RAF6

Explore the universe of human proteins at neXtProt for PRKD1: NX_Q15139

Post-translational modifications:

Phosphorylated at Ser-397 and Ser-401 by MAPK13 during regulation of insulin secretion in pancreatic beta cells.

Phosphorylated by DAPK1. Phosphorylated by ABL at Tyr-463, which primes the kinase in response to oxidative stress,

and promotes a second step activating phosphorylation at Ser-738/Ser-742 by PKRD¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q15139

4/31 DME Specific Peptides for PRKD1 (Q15139) (see all 31)

LHHPGVV

IPNNCSG

VKVPHTF

VAIKIID

PRKD1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_002733.2

ENSEMBL proteins:

ENSP00000333568 ENSP00000390535 ENSP00000447723 ENSP00000447333 ENSP00000446866

Reactome Protein details: Q15139
Human Recombinant Protein Products for PRKD1:

	EMD Millipore Purified and/or Recombinant PRKD1 Protein
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for PRKD1
	OriGene Purified Protein: PRKD1 OriGene Protein Over-expression Lysate: PRKD1 OriGene Custom Protein Services for PRKD1
	GenScript Custom Purified and Recombinant Proteins Services for PRKD1
	Novus Biologicals PRKD1 Proteins Novus Biologicals PRKD1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for PRKD1

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	--	--
GO:0005634	nucleus	IEA	--
GO:0005737	cytoplasm	IDA	--
GO:0005794	Golgi apparatus	IEA	--
GO:0005802	trans-Golgi network	IDA	19211839

PRKD1 for ontologies About GeneDecksing

PRKD1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of PRKD1
	Browse R&D Systems for Antibodies
	Cell Signaling Technology (CST) Antibodies for PRKD1 (PKD1)
	OriGene Antibodies (see all 4): PRKD1 OriGene Custom Antibody Services for PRKD1
	GenScript Superior Antibodies for PRKD1
	Novus Biologicals PRKD1 Antibodies
	Abcam antibodies for PRKD1
	Uscn Antibodies for PRKD1
	ThermoFisher Antibodies for PRKD1

Assay Products for PRKD1:

	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 PRKD1
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for PRKD1

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

PRKD1 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 Q15139

ProtoNet protein and cluster: Q15139

1 Blocks protein family: IPB001849 Pleckstrin-like

UniProtKB/Swiss-Prot: KPCD1_HUMAN, Q15139

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, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: KPCD1_HUMAN, Q15139