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

Summary

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

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_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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?

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.
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.
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.
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.
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].
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.
A possible use for DUSP9 as CIMP marker.
Title: Development of a DUSP9 methylation screening assay.
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.
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.
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 EBI GWAS CatalogPubMed
Genome-wide association study identifies three novel loci for type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70965 (e-PCR)
- UniSTS:48651

DUSP9_319 (e-PCR)
- UniSTS:277178

A005O13 (e-PCR)
- UniSTS:250

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MAP kinase serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation more info
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 RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables calmodulin-dependent protein phosphatase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS140 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine 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 phosphatase activity, metal-dependent	IEA Inferred from Electronic Annotation more info
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 chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of transcription by RNA polymerase II	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

EC 3.1.3.16

EC 3.1.3.48

NP_001386.1

EC 3.1.3.16

EC 3.1.3.48

XP_011529425.1

EC 3.1.3.16

EC 3.1.3.48

XP_047297855.1

EC 3.1.3.16

EC 3.1.3.48

XP_054182616.1

EC 3.1.3.16

EC 3.1.3.48

XP_054182617.1

EC 3.1.3.16

EC 3.1.3.48

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)

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 ...
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

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

153642441..153651326

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Alternate T2T-CHM13v2.0

Genomic

NC_060947.1 Alternate T2T-CHM13v2.0

Range

151916069..151924981

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054326641.1 → XP_054182616.1 dual specificity protein phosphatase 9 isoform X1
XM_054326642.1 → XP_054182617.1 dual specificity protein phosphatase 9 isoform X2