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    DUSP9 dual specificity phosphatase 9 [ Homo sapiens (human) ]

    Gene ID: 1852, updated on 2-Nov-2024

    Summary

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    Official Symbol
    DUSP9provided by HGNC
    Official Full Name
    dual specificity phosphatase 9provided by HGNC
    Primary source
    HGNC:HGNC:3076
    See related
    Ensembl:ENSG00000130829 MIM:300134; AllianceGenome:HGNC:3076
    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
    MKP4; MKP-4
    Summary
    The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product shows selectivity for members of the ERK family of MAP kinases and is localized to the cytoplasm and nucleus. Aberrant expression of this gene is associated with type 2 diabetes and cancer progression in several cell types. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
    Expression
    Biased expression in placenta (RPKM 41.7) and kidney (RPKM 21.4) See more
    Orthologs
    mouse all
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    Genomic context

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    See DUSP9 in Genome Data Viewer
    Location:
    Xq28
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (153642441..153651326)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (151916069..151924981)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (152907895..152916781)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene keratin 18 pseudogene 48 Neighboring gene MRFAP1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21067 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:152888899-152889398 Neighboring gene HNF4 motif-containing MPRA enhancer 232 Neighboring gene ribosomal protein L18a pseudogene 16 Neighboring gene RNA, 7SL, cytoplasmic 687, 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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population.
      Title: Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population.
    2. DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases.
      Title: DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases.
    3. DUSP9 upregulation in the placenta of gestational diabetes mellitus pregnant women may promote insulin resistance, which may correlate with the occurrence of gestational diabetes.
      Title: Expression of Dual-Specificity Phosphatase 9 in Placenta and Its Relationship with Gestational Diabetes Mellitus.
    4. Chemotherapy increased DUSP9 expression and decreased DUSP16 expression in a HIF1-dependent manner.
      Title: Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.
    5. SNP rs5945326 in DUSP9 gene may be not associated with the risk of gestational diabetes mellitus
      Title: [Association of DUSP9 gene polymorphisms with gestational diabetes mellitus].
    6. The results of this study, combined with previous studies, suggested that therapeutic intervention to increase the expression or activity of DUSP9 may enable the activation of anti-proliferation signals in malignant cells.
      Title: Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer by activating JNK signaling.
    7. A possible use for DUSP9 as CIMP marker.
      Title: Development of a DUSP9 methylation screening assay.
    8. DUSP9 protein levels were markedly suppressed in severe pre-eclampsia, but not in severe IUGR. This suppression might be attributable to the prolonged hypoxic conditions found in pre-eclampsia.
      Title: Dual specificity phosphatase 9 (DUSP9) expression is down-regulated in the severe pre-eclamptic placenta.
    9. The DUSP9 locus is a common susceptibility locus for type 2 diabetes across different ethnicities, and 6 loci identified in South Asian genome-wide association studies also have significant effect on susceptibility to Japanese type 2 diabetes.
      Title: A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population.
    10. decreased expression of DUSP-9 is associated with poor prognosis in ccRCC.
      Title: Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.
    EBI GWAS Catalog
    Genome-wide association study identifies three novel loci for type 2 diabetes.
    EBI GWAS Catalog
    Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    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 MAP kinase tyrosine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables MAP kinase tyrosine/serine/threonine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables myosin phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphoprotein phosphatase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine/serine/threonine phosphatase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein tyrosine/threonine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in ERK1 and ERK2 cascade TAS
    Traceable Author Statement
    more info
    		  
    involved_in JNK cascade TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in MAPK cascade TAS
    Traceable Author Statement
    more info
    		  
    involved_in negative regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein dephosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    dual specificity protein phosphatase 9
    Names
    map kinase phosphatase 4
    mitogen-activated protein kinase phosphatase 4
    serine/threonine specific protein phosphatase
    NP_001305432.1
    NP_001386.1
    XP_011529425.1
    XP_047297855.1
    XP_054182616.1
    XP_054182617.1

    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_001318503.2 → NP_001305432.1  dual specificity protein phosphatase 9

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AI253132, BC060837, U52111
      Consensus CDS
      CCDS14724.1
      UniProtKB/Swiss-Prot
      D3DWU5, Q99956
      UniProtKB/TrEMBL
      B2RAL9
      Related
      ENSP00000345853.3, ENST00000342782.4
      Conserved Domains (3) summary
      COG2453
      Location:193 → 342
      CDC14; Protein-tyrosine phosphatase [Signal transduction mechanisms]
      cd00127
      Location:204 → 341
      DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...
      cl00125
      Location:7 → 138
      RHOD; Rhodanese Homology Domain (RHOD); an alpha beta fold domain found duplicated in the rhodanese protein. The cysteine containing enzymatically active version of the domain is also found in the Cdc25 class of protein phosphatases and a variety of proteins ...

    2. NM_001395.4 → NP_001386.1  dual specificity protein phosphatase 9

      See identical proteins and their annotated locations for NP_001386.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AI253132, AK314250, KF459508, U52111, Y08302
      Consensus CDS
      CCDS14724.1
      UniProtKB/Swiss-Prot
      D3DWU5, Q99956
      UniProtKB/TrEMBL
      B2RAL9
      Related
      ENSP00000359186.4, ENST00000370167.8
      Conserved Domains (3) summary
      COG2453
      Location:193 → 342
      CDC14; Protein-tyrosine phosphatase [Signal transduction mechanisms]
      cd00127
      Location:204 → 341
      DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...
      cl00125
      Location:7 → 138
      RHOD; Rhodanese Homology Domain (RHOD); an alpha beta fold domain found duplicated in the rhodanese protein. The cysteine containing enzymatically active version of the domain is also found in the Cdc25 class of protein phosphatases and a variety of 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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      153642441..153651326
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011531123.2 → XP_011529425.1  dual specificity protein phosphatase 9 isoform X1

      UniProtKB/TrEMBL
      B2RAL9
      Conserved Domains (3) summary
      COG2453
      Location:224 → 373
      CDC14; Protein-tyrosine phosphatase [Signal transduction mechanisms]
      cd00127
      Location:235 → 372
      DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...
      cd01446
      Location:38 → 169
      DSP_MapKP; N-terminal regulatory rhodanese domain of dual specificity phosphatases (DSP), such as Mapk Phosphatase. This domain is believed to determine substrate specificity by binding the substrate, such as ERK2, and activating the C-terminal catalytic domain by ...

    2. XM_047441899.1 → XP_047297855.1  dual specificity protein phosphatase 9 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      151916069..151924981
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054326641.1 → XP_054182616.1  dual specificity protein phosphatase 9 isoform X1

    2. XM_054326642.1 → XP_054182617.1  dual specificity protein phosphatase 9 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q99956.1 GenPept UniProtKB/Swiss-Prot:Q99956

    Gene LinkOut

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