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    PRKD3 protein kinase D3 [ Homo sapiens (human) ]

    Gene ID: 23683, updated on 28-Oct-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
    mouse all
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    Genomic context

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    See PRKD3 in Genome Data Viewer
    Location:
    2p22.2
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (37250502..37324833, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (37257518..37331821, complement)
    RS_2024_09 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 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. [PKD3 contributes to up-regulation of prostate-specific antigen in prostate cancer cells]. Deng F, et al. Nan Fang Yi Ke Da Xue Xue Bao, 2010 Aug. PMID 20813663
    4. Influenza A virus proteins PB1 and NS1 are subject to functionally important phosphorylation by protein kinase C. Mahmoudian S, et al. J Gen Virol, 2009 Jun. PMID 19264651
    5. Selective binding of phorbol esters and diacylglycerol by individual C1 domains of the PKD family. Chen J, et al. Biochem J, 2008 Apr 15. PMID 18076381

    See all (87) 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 phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    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_2024_08

    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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