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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
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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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Related articles in PubMed

  1. Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer by activating JNK signaling. Wu F, et al. Oncol Rep, 2015 Jul. PMID 25998184
  2. Molecular cloning and functional characterization of a novel mitogen-activated protein kinase phosphatase, MKP-4. Muda M, et al. J Biol Chem, 1997 Feb 21. PMID 9030581
  3. Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4. Jeong DG, et al. Acta Crystallogr D Biol Crystallogr, 2011 Jan. PMID 21206059
  4. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma. Wu S, et al. BMC Cancer, 2011 Sep 26. PMID 21943117, Free PMC Article
  5. Dual specificity phosphatase 9 (DUSP9) expression is down-regulated in the severe pre-eclamptic placenta. Czikk MJ, et al. Placenta, 2013 Feb. PMID 23276385

See all (49) citations in PubMed

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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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 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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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

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