DUSP6

Protein identityUniProt · HPA

UniProt accession

Q16828

Gene

DUSP6

Ensembl

ENSG00000139318

Chromosome

12

Canonical length

381 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

381 residues, UniProt reviewed canonical sequence.

>Q16828|DUSP6
     1  MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI ESAINVAIPG
    61  IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE SSSDWNENTG GESVLGLLLK
   121  KLKDEGCRAF YLEGGFSKFQ AEFSLHCETN LDGSCSSSSP PLPVLGLGGL RISSDSSSDI
   181  ESDLDRDPNS ATDSDGSPLS NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT
   241  PNLPNLFENA GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS
   301  VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS SPCDNRVPAQ
   361  QLYFTTPSNQ NVYQVDSLQS T

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DUSP6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

213 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DUSP6.

Disease | AllUniProt

Conditions DUSP6 is implicated in, by any mechanism.

• Hypogonadotropic hypogonadism 19 with or without anosmia (HH19) MIM:615269

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 100 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypogonadotropic hypogonadism 19 with or without anosmia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.26

gnomAD pLI

0.98

gnomAD missense Z

1.22

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• ERK1 and ERK2 cascade
• MAPK cascade
• negative regulation of ERK1 and ERK2 cascade
• negative regulation of MAPK cascade
• peptidyl-tyrosine dephosphorylation
• positive regulation of apoptotic process
• regulation of heart growth
• response to growth factor
• response to nitrosative stress
• response to xenobiotic stimulus
• signal transduction

Molecular functions

• MAP kinase tyrosine phosphatase activity
• MAP kinase tyrosine/serine/threonine phosphatase activity
• protein serine/threonine phosphatase activity
• protein tyrosine phosphatase activity
• protein tyrosine/serine/threonine phosphatase activity
• protein tyrosine/threonine phosphatase activity

Cellular components

• cytoplasm
• cytosol
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Dual specificity phosphatase, catalytic domain
• Tyrosine-specific protein phosphatases domain
• Rhodanese-like domain
• Mitogen-activated protein (MAP) kinase phosphatase
• Dual specificity protein phosphatase domain
• Protein-tyrosine phosphatase-like
• Rhodanese-like domain superfamily
• Rhodanese-like domain
• Dual specificity phosphatase, catalytic domain

KeywordsUniProt

• Cytoplasm
• Hydrolase
• Hypogonadotropic hypogonadism
• Kallmann syndrome
• Protein phosphatase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of DUSP6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAPK1
• MAPK3