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FLASH GENE

Symbol

DUSP6

contributors: mct - updated : 27-10-2011

HGNC name	dual specificity phosphatase 6
HGNC id	3072

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	12q21.33      Physical location : 89.741.838 - 89.746.296
Synonym name	mitogen activated protein kinase (MAPK) phosphatase 6
	MAP kinase phosphatase 3
Synonym symbol(s)	MKP3, PYST1, VH-6
EC.number	3.1.3.48/ 3.1.3.16

DNA

TYPE	functioning gene
STRUCTURE	4.46 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	intron 1 of DUSP6 plays a crucial role in transcriptional regulation of DUSP6 in a feedback loop manner responding to MAPK1 via ETS2 in human cells (Furukawa 2008)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	two transcripts (Furukawa)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001946 3 - 2842 42.1 381 - 1998 9788880 NM_022652 2 - 2404 26.3 235 - 1998 9788880

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     highly Lymphoid/Immune spleen       highly Respiratory respiratory tract trachea     highly Urinary bladder       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two N terminal CH2 domains
	an extended active site sequence motif conserved in dual specificity phosphatases
	a rhodanese domain
	a tyrosine-protein phosphatase domain

HOMOLOGY

Homologene

FAMILY

dual specificity protein phosphatase subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	inactivating map kinases and having a specificity for the ERK family
	having a function in shuttles between the nucleus and cytoplasm
	important regulator of PDGF-induced Erk phosphorylation acting in both a rapid positive feed-forward and a later negative feed-back loop
	growth suppressor whose inactivation could promote the progression of lung cancer
	DUSP5 and DUSP6 selectively control ERK pathway activity and proliferation
	protective role of the MAPK signaling in oligodendrocyte death and DUSP6 is relevant negative regulator of this survival pathway
	role of DUSP6 in neuronal cell death
	dephosphorylates phosphotyrosine and phosphothreonine residues on extracellular signal-regulated kinase (ERK1/2; MAPK1/2) to inactivate the ERK1/2 kinase

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein

inactivating ERK2

cell & other

REGULATION

Other	regulated by ETS2 (ETS2 is a key regulatory factor in the transcriptional control of DUSP6 (Dusp6) in responding to activity of MAPK1) (Furukawa (2008)
	PEDRE controls pluripotent state-specific expression of DUSP6 (Zhang, 2009)
	post-transcriptional regulation is a key process in the control of DUSP6 expression

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in primary pancreatic cancer tumoral     --over   exerts a tumor-promoting role in human glioblastomas exacerbating the malignant phenotype constitutional     --over   in optic nerves from multiple sclerosis patients before the appearance of evident damage in this structure

Susceptibility

to congenital Hypogonadotropic Hypogonadism

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology autoimmune multiple sclerosis targeting Dusp6 may be a useful strategy to prevent oligodendrocyte death in multiple sclerosis and other diseases involving CNS white matter.

ANIMAL & CELL MODELS