DUSP4 dual specificity phosphatase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DUSP4provided by HGNC
Official Full Name: dual specificity phosphatase 4provided by HGNC
Primary source: HGNC:HGNC:3070
See related: Ensembl:ENSG00000120875 MIM:602747; AllianceGenome:HGNC:3070
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: TYP; HVH2; MKP2; MKP-2
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 are 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 inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported. [provided by RefSeq, Jul 2008]
Expression: Broad expression in stomach (RPKM 8.5), gall bladder (RPKM 5.0) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8p12

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (29333064..29350684, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (29611341..29628961, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (29190581..29208201, complement)

Chromosome 8 - NC_000008.11 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?

Dual-Specificity Phosphatase 4 Promotes Malignant Features in Colorectal Cancer Through Cyclic-AMP Response Element Binding Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta Activation.
Title: Dual-Specificity Phosphatase 4 Promotes Malignant Features in Colorectal Cancer Through Cyclic-AMP Response Element Binding Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta Activation.
Dual specific phosphatase 4 suppresses ferroptosis and enhances sorafenib resistance in hepatocellular carcinoma.
Title: Dual specific phosphatase 4 suppresses ferroptosis and enhances sorafenib resistance in hepatocellular carcinoma.
DUSP4 maintains the survival and LSD1 protein stability in esophageal squamous cell carcinoma cells by inhibiting JNK signaling-dependent autophagy.
Title: DUSP4 maintains the survival and LSD1 protein stability in esophageal squamous cell carcinoma cells by inhibiting JNK signaling-dependent autophagy.
Proteomic Signaling of Dual-Specificity Phosphatase 4 (DUSP4) in Alzheimer's Disease.
Title: Proteomic Signaling of Dual-Specificity Phosphatase 4 (DUSP4) in Alzheimer's Disease.
ARID1A loss activates MAPK signaling via DUSP4 downregulation.
Title: ARID1A loss activates MAPK signaling via DUSP4 downregulation.
An integrative analysis of the single-cell transcriptome identifies DUSP4 as an exhaustion-associated gene in tumor-infiltrating CD8+ T cells.
Title: An integrative analysis of the single-cell transcriptome identifies DUSP4 as an exhaustion-associated gene in tumor-infiltrating CD8+ T cells.
DUSP4 inhibits autophagic cell death and apoptosis in colorectal cancer by regulating BCL2-Beclin1/Bax signaling.
Title: DUSP4 inhibits autophagic cell death and apoptosis in colorectal cancer by regulating BCL2-Beclin1/Bax signaling.
Investigating the Role of DUSP4 in Uveal Melanoma.
Title: Investigating the Role of DUSP4 in Uveal Melanoma.
Low expression of DUSP4 expression predicts unfavorable prognosis in gallbladder adenocarcinoma.
Title: Low expression of DUSP4 expression predicts unfavorable prognosis in gallbladder adenocarcinoma.
DUSP4 Inactivation Leads to Reduced Extracellular SignalRegulated Kinase Activity through Upregulation of DUSP6 in Melanoma Cells.
Title: DUSP4 Inactivation Leads to Reduced Extracellular Signal‒Regulated Kinase Activity through Upregulation of DUSP6 in Melanoma Cells.

Submit: New GeneRIF Correction See all GeneRIFs (64)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association of lipid-lowering response to statins in combined study populations. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Primary human Muller glia cells treated with HIV-1 clade B Tat, but not with clade C Tat, upregulate the expression of MKP-2 protein	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH36102 (e-PCR)
- UniSTS:56590

RH18016 (e-PCR)
- UniSTS:50766

DUSP4_V11 (e-PCR)
- UniSTS:462168

DUSP4_590.2 (e-PCR)
- UniSTS:462168

A004W39 (e-PCR)
- UniSTS:2165

WI-22140 (e-PCR)
- UniSTS:69753

D8S1424E (e-PCR)
- UniSTS:151213

SGC35388 (e-PCR)
- UniSTS:47321

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MAP kinase serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
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 phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphoprotein phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
enables protein tyrosine phosphatase activity, metal-dependent	IEA Inferred from Electronic Annotation more info
enables protein tyrosine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in endoderm formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
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
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: dual specificity protein phosphatase 4

Names: MAP kinase phosphatase 2; VH1 homologous phosphatase 2; dual specificity protein phosphatase hVH2; mitogen-activated protein kinase phosphatase 2; serine/threonine specific protein phosphatase

NP_001385.1

EC 3.1.3.16

EC 3.1.3.48

NP_476499.1

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_001394.7 → NP_001385.1 dual specificity protein phosphatase 4 isoform 1

See identical proteins and their annotated locations for NP_001385.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript but encodes the longer isoform (1).

Source sequence(s)

AC084262, AK314820, AL137704, BC012900, DA645190

Consensus CDS

CCDS6072.1

UniProtKB/Swiss-Prot

B2RBU5, D3DSU4, G5E930, Q13115, Q13524

UniProtKB/TrEMBL

Q13649

Related

ENSP00000240100.2, ENST00000240100.7

Conserved Domains (2) summary

cd00127
Location:195 → 331

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:9 → 158

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 ...
NM_057158.4 → NP_476499.1 dual specificity protein phosphatase 4 isoform 2

See identical proteins and their annotated locations for NP_476499.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC084262, AL137704, BC012900

Consensus CDS

CCDS6073.1

UniProtKB/Swiss-Prot

Q13115

Related

ENSP00000240101.2, ENST00000240101.2

Conserved Domains (1) summary

cd00127
Location:104 → 240

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 ...