DUSP2 dual specificity phosphatase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DUSP2provided by HGNC
Official Full Name: dual specificity phosphatase 2provided by HGNC
Primary source: HGNC:HGNC:3068
See related: Ensembl:ENSG00000158050 MIM:603068; AllianceGenome:HGNC:3068
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: PAC1; PAC-1
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 and ERK2, is predominantly expressed in hematopoietic tissues, and is localized in the nucleus. [provided by RefSeq, Jul 2008]
Expression: Biased expression in bone marrow (RPKM 49.4), lymph node (RPKM 22.5) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q11.2

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (96143169..96145440, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (96649773..96656541, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (96808908..96811179, complement)

Chromosome 2 - NC_000002.12 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
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?

Retinoblastoma-associated protein is important for TRIM24-mediated activation of the mTOR signaling pathway through DUSP2 action in prostate cancer.
Title: Retinoblastoma-associated protein is important for TRIM24-mediated activation of the mTOR signaling pathway through DUSP2 action in prostate cancer.
Down-regulation of DUSP2 expression in serous ovarian carcinoma was an independent risk factor for patient survival.
Title: Expression of Dual-Specificity Phosphatase 2 (DUSP2) in Patients with Serous Ovarian Carcinoma and in SKOV3 and OVCAR3 Cells In Vitro.
PAC1 is selectively upregulated in exhausted tumor-infiltrating lymphocytes and is associated with poor prognosis of patients with cancer. PAC1(hi) effector T cells lose their proliferative and effector capacities and convert into exhausted T cells.
Title: The phosphatase PAC1 acts as a T cell suppressor and attenuates host antitumor immunity.
Taken together, our findings for the first time suggested DUSP2 as a progression and prognosis biomarker for bladder cancer.
Title: Loss of DUSP2 predicts a poor prognosis in patients with bladder cancer.
Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2 has been reported.
Title: Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2.
hypoxia-induced IL-6 production in endometriotic lesions is mediated via downregulation of DUSP2, which causes aberrant activation of STAT3 signaling pathway and helps the endometriotic cells survive under the ectopic environment
Title: Hypoxia-inhibited DUSP2 expression promotes IL-6/STAT3 signaling in endometriosis.
Authors report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer.
Title: Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness.
Hypoxia inhibits DUSP2 expression in colon cancer, leading to up-regulation of IL-8, which facilitates angiogenesis and tumour metastasis.
Title: Loss of dual-specificity phosphatase-2 promotes angiogenesis and metastasis via up-regulation of interleukin-8 in colon cancer.
Our data show that aberrant epigenetic inactivation of DUSP2 occurs in carcinogenesis and that CTCF is involved in the epigenetic regulation of DUSP2 expression.
Title: The dual specificity phosphatase 2 gene is hypermethylated in human cancer and regulated by epigenetic mechanisms.
Highly recurrent mutation of DUSP2 is associated with nodular lymphocyte predominant Hodgkin lymphoma.
Title: Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma.

Submit: New GeneRIF Correction See all GeneRIFs (23)

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

RH75846 (e-PCR)
- UniSTS:85268

PMC343947P2 (e-PCR)
- UniSTS:273200

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MAP kinase serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation 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 mitogen-activated protein kinase binding	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	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	TAS Traceable Author Statement more info	PubMed
enables protein tyrosine phosphatase activity, metal-dependent	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in endoderm formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of MAPK 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
located_in nuclear membrane	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: dual specificity protein phosphatase 2

Names: dual specificity protein phosphatase PAC-1; serine/threonine specific protein phosphatase

NP_004409.1

EC 3.1.3.16

EC 3.1.3.48

XP_016859035.1

EC 3.1.3.16

EC 3.1.3.48

XP_054196891.1

EC 3.1.3.16

EC 3.1.3.48

XP_054196892.1

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_004418.4 → NP_004409.1 dual specificity protein phosphatase 2

See identical proteins and their annotated locations for NP_004409.1

Status: REVIEWED

Source sequence(s)

BC007771, DB475178

Consensus CDS

CCDS2016.1

UniProtKB/Swiss-Prot

Q05923, Q53T45

Related

ENSP00000288943.4, ENST00000288943.5

Conserved Domains (2) summary

cd00127
Location:172 → 308

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:8 → 143

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 ...

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_000002.12 Reference GRCh38.p14 Primary Assembly

Range

96143169..96145440 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017003546.2 → XP_016859035.1 dual specificity protein phosphatase 2 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

96649773..96656541 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054340916.1 → XP_054196891.1 dual specificity protein phosphatase 2 isoform X2
XM_054340917.1 → XP_054196892.1 dual specificity protein phosphatase 2 isoform X3