DUSP3 dual specificity phosphatase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DUSP3provided by HGNC
Official Full Name: dual specificity phosphatase 3provided by HGNC
Primary source: HGNC:HGNC:3069
See related: Ensembl:ENSG00000108861 MIM:600183; AllianceGenome:HGNC:3069
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: VHR
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 maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in heart (RPKM 57.5), esophagus (RPKM 29.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q21.31

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (43766125..43778977, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (44618675..44631521, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (41843493..41856345, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

The role of dual-specificity phosphatase 3 in melanocytic oncogenesis.
Title: The role of dual-specificity phosphatase 3 in melanocytic oncogenesis.
DUSP3 maintains genomic stability and cell proliferation by modulating NER pathway and cell cycle regulatory proteins.
Title: DUSP3 maintains genomic stability and cell proliferation by modulating NER pathway and cell cycle regulatory proteins.
Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase 3.
Title: Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase 3.
Allosteric Impact of the Variable Insert Loop in Vaccinia H1-Related (VHR) Phosphatase.
Title: Allosteric Impact of the Variable Insert Loop in Vaccinia H1-Related (VHR) Phosphatase.
Study demonstrated that miR-1915-3p might promote the proliferation and metastasis of breast cancer by repression of DUSP3 and serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer.
Title: Identification of serum miR-1915-3p and miR-455-3p as biomarkers for breast cancer.
Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis.
Title: VRK3-mediated nuclear localization of HSP70 prevents glutamate excitotoxicity-induced apoptosis and Aβ accumulation via enhancement of ERK phosphatase VHR activity.
Data indicated that regulating non-receptor tyrosine kinase FAK and cell migration is a newly revealed function of VHR/DUSP3.
Title: Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.
The loss of DUSP3 activity markedly increases gamma radiation-induced DNA strand breaks, suggesting a potential novel role for DUSP3 in DNA repair.
Title: Loss of DUSP3 activity radiosensitizes human tumor cell lines via attenuation of DNA repair pathways.
In PTP1B and VHR, two new allosteric clusters were identified in each enzyme.
Title: Leveraging Reciprocity to Identify and Characterize Unknown Allosteric Sites in Protein Tyrosine Phosphatases.
In the phosphatase-silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis.
Title: Reduced levels of Dusp3/Vhr phosphatase impair normal spindle bipolarity in an Erk1/2 activity-dependent manner.

Submit: New GeneRIF Correction See all GeneRIFs (26)

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

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

RH48877 (e-PCR)
- UniSTS:38658

SHGC-2457 (e-PCR)
- UniSTS:167710

SGC30297 (e-PCR)
- UniSTS:35383

D17S814E (e-PCR)
- UniSTS:32581

SGC30031 (e-PCR)
- UniSTS:8541

STS-N67742 (e-PCR)
- UniSTS:21647

STS-N24113 (e-PCR)
- UniSTS:72343

D17S1216 (e-PCR)
- UniSTS:33971

HUM0C12C02 (e-PCR)
- UniSTS:55733

DUSP3_588 (e-PCR)
- UniSTS:277176

A006E16 (e-PCR)
- UniSTS:46265

RH78942 (e-PCR)
- UniSTS:34754

HUM000S655 (e-PCR)
- UniSTS:67532

D17S814E (e-PCR)
- UniSTS:147424

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MAP kinase phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables MAP kinase phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cytoskeletal protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase 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	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
enables protein tyrosine/serine/threonine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein tyrosine/serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine/serine/threonine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables receptor tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to epidermal growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of JNK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of T cell receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epidermal growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in peptidyl-tyrosine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-tyrosine dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of focal adhesion disassembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed

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	IDA Inferred from Direct Assay more info	PubMed
located_in immunological synapse	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement 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 3

Names: dual specificity protein phosphatase VHR; serine/threonine specific protein phosphatase; vaccinia H1-related phosphatase; vaccinia virus phosphatase VH1-related

NP_004081.1

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.