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PRKD3 protein kinase D3 [ Homo sapiens (human) ]

Gene ID: 23683, updated on 3-Apr-2024

Summary

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Official Symbol
PRKD3provided by HGNC
Official Full Name
protein kinase D3provided by HGNC
Primary source
HGNC:HGNC:9408
See related
Ensembl:ENSG00000115825 MIM:607077; AllianceGenome:HGNC:9408
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EPK2; PKD3; PRKCN; PKC-NU; nPKC-NU
Summary
This gene belongs to the multigene protein kinase D family of serine/threonine kinases, which bind diacylglycerol and phorbol esters. Members of this family are characterized by an N-terminal regulatory domain comprised of a tandem repeat of cysteine-rich zinc-finger motifs and a pleckstrin domain. The C-terminal region contains the catalytic domain and is distantly related to calcium-regulated kinases. Catalytic activity of this enzyme promotes its nuclear localization. This protein has been implicated in a variety of functions including negative regulation of human airway epithelial barrier formation, growth regulation of breast and prostate cancer cells, and vesicle trafficking. [provided by RefSeq, Jan 2015]
Expression
Ubiquitous expression in lymph node (RPKM 16.0), testis (RPKM 14.3) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
2p22.2
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (37250502..37324833, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (37257518..37331821, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (37477645..37551976, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene sulfotransferase family 6B member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11355 Neighboring gene ribosomal protein L31 pseudogene 16 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:37431745-37432548 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:37432549-37433353 Neighboring gene CEBPZ opposite strand Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:37441863-37443062 Neighboring gene CCAAT enhancer binding protein zeta Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:37453022-37453626 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:37458084-37459283 Neighboring gene NADH:ubiquinone oxidoreductase complex assembly factor 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15582 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11356 Neighboring gene PRKD3 divergent transcript Neighboring gene RNA, U6 small nuclear 939, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration. Varga A, et al. Cells, 2023 Jan 4. PMID 36672148, Free PMC Article
  2. The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells. Lieb WS, et al. Int J Cancer, 2020 Jun 15. PMID 31745977, Free PMC Article
  3. Oncogenic Protein Kinase D3 Regulating Networks in Invasive Breast Cancer. Liu Y, et al. Int J Biol Sci, 2017. PMID 28656000, Free PMC Article
  4. Higher PKD3 expression in hepatocellular carcinoma (HCC) tissues predicts poorer prognosis for HCC patients. Yang H, et al. Clin Res Hepatol Gastroenterol, 2017 Oct. PMID 28363424
  5. Protein kinase D3 is essential for prostratin-activated transcription of integrated HIV-1 provirus promoter via NF-κB signaling pathway. Wang H, et al. Biomed Res Int, 2014. PMID 25136641, Free PMC Article

See all (86) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.
    Title: Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.
  2. PRKD3 promotes malignant progression of OSCC by downregulating KLF16 expression.
    Title: PRKD3 promotes malignant progression of OSCC by downregulating KLF16 expression.
  3. Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice.
    Title: Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice.
  4. Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c-MYC axis in breast cancer.
    Title: Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c-MYC axis in breast cancer.
  5. The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells.
    Title: The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells.
  6. Protein kinase D3 regulates the expression of the immunosuppressive protein, PDL1, through STAT1/STAT3 signaling.
    Title: Protein kinase D3 regulates the expression of the immunosuppressive protein, PD‑L1, through STAT1/STAT3 signaling.
  7. The PRKD3 up-regulated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and activated glycolysis as shown by increased glucose consumption and lactate production.
    Title: Protein kinase D3 promotes gastric cancer development through p65/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 activation of glycolysis.
  8. KD2 and PKD3 were the two major isoforms of PKD overexpressed in breast cancer. Suppressing either PKD2 or PKD3 was able to reduce breast cancer cell proliferation and metastasis.
    Title: Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer.
  9. exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-kappaB signaling pathway, leading to AP-1 or NF-kappaB binding to the promoter of scf, ccl5 and ccl11.
    Title: Protein kinase Ds promote tumor angiogenesis through mast cell recruitment and expression of angiogenic factors in prostate cancer microenvironment.
  10. Our findings suggest that abnormal PKD3 expression might contribute to hepatocellular carcinoma progression. Furthermore, high PKD3 expression predicts a poor prognosis in hepatocellular carcinoma patients after hepatectomy
    Title: Higher PKD3 expression in hepatocellular carcinoma (HCC) tissues predicts poorer prognosis for HCC patients.
Submit: New GeneRIF Correction See all GeneRIFs (35)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
EBI GWAS Catalog
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Protein kinase C is required for HIV-1 Tat-mediated transactivation of the viral LTR promoter, indicating protein kinase C regulates the process of HIV-1 transactivation and may play a role in the transition of HIV from latency to productive growth PubMed
tat Protein kinase C phosphorylates HIV-1 Tat on serine residue 46 PubMed
tat HIV-1 Tat activates protein kinase C, resulting in the induction of TNF-alpha, IL-6 and IL-10 expression and the secretion of MCP-1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables diacylglycerol-dependent serine/threonine kinase activity TAS
Traceable Author Statement
more info
  
enables kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in phospholipase C-activating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein kinase C-activating G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein phosphorylation TAS
Traceable Author Statement
more info
 PubMed 
involved_in sphingolipid biosynthetic process TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
serine/threonine-protein kinase D3
Names
protein kinase C nu type
protein kinase EPK2
NP_005804.1
XP_005264294.1
XP_005264295.1
XP_016859233.1
XP_047299808.1
XP_047299809.1
XP_047299810.1
XP_047299811.1
XP_047299812.1
XP_054197212.1
XP_054197213.1
XP_054197214.1
XP_054197215.1
XP_054197216.1
XP_054197217.1
XP_054197218.1
XP_054197219.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_005813.6 → NP_005804.1  serine/threonine-protein kinase D3

    See identical proteins and their annotated locations for NP_005804.1

    Status: REVIEWED

    Source sequence(s)
    AC007390, AC007391
    Consensus CDS
    CCDS1789.1
    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8
    UniProtKB/TrEMBL
    A0A1S5UZ27
    Related
    ENSP00000234179.2, ENST00000234179.8
    Conserved Domains (4) summary
    cd01239
    Location:410 → 534
    PH_PKD; Protein kinase D (PKD/PKCmu) pleckstrin homology (PH) domain
    cd14082
    Location:572 → 831
    STKc_PKD; Catalytic domain of the Serine/Threonine kinase, Protein Kinase D
    cd20841
    Location:145 → 219
    C1_PKD3_rpt1; first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins
    cd20844
    Location:267 → 335
    C1_PKD3_rpt2; second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    37250502..37324833 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005264238.4 → XP_005264295.1  serine/threonine-protein kinase D3 isoform X2

    See identical proteins and their annotated locations for XP_005264295.1

    UniProtKB/TrEMBL
    A0A1S5UZ27
    Conserved Domains (5) summary
    smart00220
    Location:476 → 728
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00029
    Location:168 → 217
    C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
    cd01239
    Location:306 → 430
    PH_PKD; Protein kinase D (PKD/PKCmu) pleckstrin homology (PH) domain
    cd14082
    Location:468 → 727
    STKc_PKD; Catalytic domain of the Serine/Threonine kinase, Protein Kinase D
    pfam00130
    Location:55 → 100
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

  2. XM_047443853.1 → XP_047299809.1  serine/threonine-protein kinase D3 isoform X1

    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8
    Related
    ENSP00000368356.1, ENST00000379066.5

  3. XM_005264237.5 → XP_005264294.1  serine/threonine-protein kinase D3 isoform X1

    See identical proteins and their annotated locations for XP_005264294.1

    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8
    UniProtKB/TrEMBL
    A0A1S5UZ27
    Conserved Domains (4) summary
    cd01239
    Location:410 → 534
    PH_PKD; Protein kinase D (PKD/PKCmu) pleckstrin homology (PH) domain
    cd14082
    Location:572 → 831
    STKc_PKD; Catalytic domain of the Serine/Threonine kinase, Protein Kinase D
    cd20841
    Location:145 → 219
    C1_PKD3_rpt1; first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins
    cd20844
    Location:267 → 335
    C1_PKD3_rpt2; second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins

  4. XM_047443852.1 → XP_047299808.1  serine/threonine-protein kinase D3 isoform X1

    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8

  5. XM_017003744.3 → XP_016859233.1  serine/threonine-protein kinase D3 isoform X4

    UniProtKB/TrEMBL
    B3KNJ2
    Conserved Domains (3) summary
    cd00029
    Location:13 → 62
    C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
    cd01239
    Location:151 → 275
    PH_PKD; Protein kinase D (PKD/PKCmu) pleckstrin homology (PH) domain
    cd14082
    Location:313 → 572
    STKc_PKD; Catalytic domain of the Serine/Threonine kinase, Protein Kinase D

  6. XM_047443854.1 → XP_047299810.1  serine/threonine-protein kinase D3 isoform X3

  7. XM_047443855.1 → XP_047299811.1  serine/threonine-protein kinase D3 isoform X4

  8. XM_047443856.1 → XP_047299812.1  serine/threonine-protein kinase D3 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    37257518..37331821 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341240.1 → XP_054197215.1  serine/threonine-protein kinase D3 isoform X2

  2. XM_054341239.1 → XP_054197214.1  serine/threonine-protein kinase D3 isoform X1

    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8

  3. XM_054341238.1 → XP_054197213.1  serine/threonine-protein kinase D3 isoform X1

    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8

  4. XM_054341237.1 → XP_054197212.1  serine/threonine-protein kinase D3 isoform X1

    UniProtKB/Swiss-Prot
    D6W587, O94806, Q53TR7, Q8NEL8

  5. XM_054341243.1 → XP_054197218.1  serine/threonine-protein kinase D3 isoform X4

  6. XM_054341241.1 → XP_054197216.1  serine/threonine-protein kinase D3 isoform X3

  7. XM_054341242.1 → XP_054197217.1  serine/threonine-protein kinase D3 isoform X4

  8. XM_054341244.1 → XP_054197219.1  serine/threonine-protein kinase D3 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O94806.1 GenPept UniProtKB/Swiss-Prot:O94806

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