DUSP6 dual specificity phosphatase 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DUSP6provided by HGNC
Official Full Name: dual specificity phosphatase 6provided by HGNC
Primary source: HGNC:HGNC:3072
See related: Ensembl:ENSG00000139318 MIM:602748; AllianceGenome:HGNC:3072
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: HH19; MKP3; PYST1
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 ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas, and unlike most other members of this family, is localized in the cytoplasm. Mutations in this gene have been associated with congenital hypogonadotropic hypogonadism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]
Expression: Ubiquitous expression in bone marrow (RPKM 46.5), fat (RPKM 44.7) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q21.33

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (89347235..89352501, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (89329179..89334445, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (89741012..89746278, complement)

Chromosome 12 - NC_000012.12 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 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?

Functional Role of DUSP6 in the EGFR-mediated Progression of Head and Neck Squamous Cell Carcinoma.
Title: Functional Role of DUSP6 in the EGFR-mediated Progression of Head and Neck Squamous Cell Carcinoma.
Long non-coding RNA NORAD regulates megakaryocyte differentiation and proplatelet formation via the DUSP6/ERK signaling pathway.
Title: Long non-coding RNA NORAD regulates megakaryocyte differentiation and proplatelet formation via the DUSP6/ERK signaling pathway.
DUSP6 is a memory retention feedback regulator of ERK signaling for cellular resilience of human pluripotent stem cells in response to dissociation.
Title: DUSP6 is a memory retention feedback regulator of ERK signaling for cellular resilience of human pluripotent stem cells in response to dissociation.
N6-methyadenosine modified SUV39H2 regulates homologous recombination through epigenetic repression of DUSP6 in gastric cancer.
Title: N6-methyadenosine modified SUV39H2 regulates homologous recombination through epigenetic repression of DUSP6 in gastric cancer.
SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma.
Title: SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma.
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.
microRNA-211-5p predicts the progression of postmenopausal osteoporosis and attenuates osteogenesis by targeting dual specific phosphatase 6.
Title: microRNA-211-5p predicts the progression of postmenopausal osteoporosis and attenuates osteogenesis by targeting dual specific phosphatase 6.
Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis.
Title: Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis.
Knockdown of TRIM9 attenuates irinotecaninduced intestinal mucositis in IEC6 cells by regulating DUSP6 expression via the P38 pathway.
Title: Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway.
DUSP6 regulates radiosensitivity in glioblastoma by modulating the recruitment of phosphorylated DNAPKcs at DNA double-strand breaks.
Title: DUSP6 regulates radiosensitivity in glioblastoma by modulating the recruitment of phosphorylated DNAPKcs at DNA double-strand breaks.

Submit: New GeneRIF Correction See all GeneRIFs (91)

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

Associated conditions

Description	Tests
Hypogonadotropic hypogonadism 19 with or without anosmia MedGen: C3808981 OMIM: 615269 GeneReviews: Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency	Compare labs
Hypogonadotropic hypogonadism 7 with or without anosmia MedGen: C0342384 OMIM: 146110 GeneReviews: Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency	Compare labs

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

D12S1567 (e-PCR)
- UniSTS:54869

DUSP6_594 (e-PCR)
- UniSTS:462169

WI-14395 (e-PCR)
- UniSTS:20122

D12S1400 (e-PCR)
- UniSTS:1704

WI-18566 (e-PCR)
- UniSTS:2230

Readthrough POC1B-DUSP6

Readthrough gene: POC1B-DUSP6, Included gene: POC1B

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 MAP kinase tyrosine/serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine phosphatase activity	TAS Traceable Author Statement 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 MAPK cascade	TAS Traceable Author Statement more info
involved_in cell differentiation	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 negative regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-tyrosine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of heart growth	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to growth factor	IEA Inferred from Electronic Annotation more info
involved_in response to nitrosative stress	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	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 cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: dual specificity protein phosphatase 6

Names: MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-activated protein kinase phosphatase 3; serine/threonine specific protein phosphatase

NP_001937.2

EC 3.1.3.16

EC 3.1.3.48

NP_073143.2

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.

Genomic

NG_033915.1 RefSeqGene

Range

5359..10625

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001946.4 → NP_001937.2 dual specificity protein phosphatase 6 isoform a

See identical proteins and their annotated locations for NP_001937.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AC024909, BC003143, BC037236, BF087219, DA105027

Consensus CDS

CCDS9033.1

UniProtKB/Swiss-Prot

O75109, Q16828, Q53Y75, Q9BSH6

UniProtKB/TrEMBL

B5BU29

Related

ENSP00000279488.6, ENST00000279488.8

Conserved Domains (2) summary

cd01446
Location:17 → 147

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 ...

cd14566
Location:207 → 343

DSP_MKP_classII; dual specificity phosphatase domain of class II mitogen-activated protein kinase phosphatase
NM_022652.4 → NP_073143.2 dual specificity protein phosphatase 6 isoform b

See identical proteins and their annotated locations for NP_073143.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1. The resulting shorter isoform (b) lacks an internal protein segment compared to isoform a.

Source sequence(s)

AC024909, AK222882, BC003143, BC037236, BF087219, DA105027

Consensus CDS

CCDS9034.1

UniProtKB/TrEMBL

Q53GP9

Related

ENSP00000307835.6, ENST00000308385.6

Conserved Domains (2) summary

cd01446
Location:17 → 134

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 ...

cl28904
Location:134 → 197

PTP_DSP_cys; cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily