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Protein

Dual specificity protein phosphatase 6

Gene

DUSP6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inactivates MAP kinases. Has a specificity for the ERK family (PubMed:9858808). Plays an important role in alleviating chronic postoperative pain. Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (By similarity).By similarity1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei293Phosphocysteine intermediate1 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

BioCyciZFISH:HS06607-MONOMER.
BRENDAi3.1.3.16. 2681.
3.1.3.48. 2681.
ReactomeiR-HSA-112409. RAF-independent MAPK1/3 activation.
R-HSA-202670. ERKs are inactivated.
R-HSA-5675221. Negative regulation of MAPK pathway.
SignaLinkiQ16828.
SIGNORiQ16828.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein phosphatase 6 (EC:3.1.3.16, EC:3.1.3.48)
Alternative name(s):
Dual specificity protein phosphatase PYST1
Mitogen-activated protein kinase phosphatase 3
Short name:
MAP kinase phosphatase 3
Short name:
MKP-3
Gene namesi
Name:DUSP6
Synonyms:MKP3, PYST1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3072. DUSP6.

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 19 with or without anosmia (HH19)1 Publication
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in DUSP6 also have a heterozygous mutation in another HH-associated gene including FGFR1 and SPRY4 (PubMed:23643382).1 Publication
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:615269
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06994377F → I in HH19. 1 PublicationCorresponds to variant rs587776978dbSNPEnsembl.1
Natural variantiVAR_069944182S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. 1 PublicationCorresponds to variant rs139318648dbSNPEnsembl.1
Natural variantiVAR_069945189N → S in HH19. 1 PublicationCorresponds to variant rs143946794dbSNPEnsembl.1
Natural variantiVAR_069946346T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. 1 PublicationCorresponds to variant rs146089505dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

DisGeNETi1848.
MalaCardsiDUSP6.
MIMi615269. phenotype.
OpenTargetsiENSG00000139318.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA27529.

Chemistry databases

ChEMBLiCHEMBL1250381.

Polymorphism and mutation databases

BioMutaiDUSP6.
DMDMi108860971.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000948041 – 381Dual specificity protein phosphatase 6Add BLAST381

Proteomic databases

MaxQBiQ16828.
PaxDbiQ16828.
PeptideAtlasiQ16828.
PRIDEiQ16828.

PTM databases

DEPODiQ16828.
iPTMnetiQ16828.
PhosphoSitePlusiQ16828.

Expressioni

Gene expression databases

BgeeiENSG00000139318.
CleanExiHS_DUSP6.
ExpressionAtlasiQ16828. baseline and differential.
GenevisibleiQ16828. HS.

Organism-specific databases

HPAiCAB017566.
HPA053188.

Interactioni

Protein-protein interaction databases

BioGridi108181. 10 interactors.
IntActiQ16828. 6 interactors.
MINTiMINT-1442837.
STRINGi9606.ENSP00000279488.

Chemistry databases

BindingDBiQ16828.

Structurei

Secondary structure

1381
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 12Combined sources6
Beta strandi15 – 18Combined sources4
Helixi23 – 29Combined sources7
Beta strandi31 – 33Combined sources3
Beta strandi35 – 37Combined sources3
Helixi43 – 48Combined sources6
Beta strandi50 – 52Combined sources3
Helixi61 – 64Combined sources4
Turni73 – 76Combined sources4
Helixi81 – 88Combined sources8
Beta strandi95 – 97Combined sources3
Beta strandi101 – 105Combined sources5
Helixi114 – 124Combined sources11
Helixi136 – 143Combined sources8
Beta strandi149 – 152Combined sources4
Beta strandi208 – 211Combined sources4
Beta strandi214 – 217Combined sources4
Helixi225 – 230Combined sources6
Beta strandi233 – 238Combined sources6
Beta strandi246 – 250Combined sources5
Beta strandi253 – 257Combined sources5
Helixi269 – 271Combined sources3
Helixi272 – 284Combined sources13
Beta strandi288 – 292Combined sources5
Helixi298 – 312Combined sources15
Helixi316 – 326Combined sources11
Helixi337 – 345Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HZMNMR-A1-154[»]
1MKPX-ray2.35A205-347[»]
ProteinModelPortaliQ16828.
SMRiQ16828.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16828.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 148RhodanesePROSITE-ProRule annotationAdd BLAST119
Domaini206 – 381Tyrosine-protein phosphataseAdd BLAST176

Sequence similaritiesi

Contains 1 rhodanese domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1717. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00760000118902.
HOGENOMiHOG000294079.
HOVERGENiHBG007347.
InParanoidiQ16828.
KOiK04459.
OMAiRDWNENT.
OrthoDBiEOG091G0249.
PhylomeDBiQ16828.
TreeFamiTF105122.

Family and domain databases

CDDicd00127. DSPc. 1 hit.
Gene3Di3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR008343. MKP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR001763. Rhodanese-like_dom.
IPR000387. TYR_PHOSPHATASE_dom.
IPR020422. TYR_PHOSPHATASE_DUAL_dom.
[Graphical view]
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiPF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PIRSFiPIRSF000939. MAPK_Ptase. 1 hit.
PRINTSiPR01764. MAPKPHPHTASE.
SMARTiSM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF52821. SSF52821. 1 hit.
PROSITEiPS50206. RHODANESE_3. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16828-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI
60 70 80 90 100
ESAINVAIPG IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE
110 120 130 140 150
SSSDWNENTG GESVLGLLLK KLKDEGCRAF YLEGGFSKFQ AEFSLHCETN
160 170 180 190 200
LDGSCSSSSP PLPVLGLGGL RISSDSSSDI ESDLDRDPNS ATDSDGSPLS
210 220 230 240 250
NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT PNLPNLFENA
260 270 280 290 300
GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS
310 320 330 340 350
VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS
360 370 380
SPCDNRVPAQ QLYFTTPSNQ NVYQVDSLQS T
Length:381
Mass (Da):42,320
Last modified:May 30, 2006 - v2
Checksum:i386612227F5D3B2A
GO
Isoform 2 (identifier: Q16828-2) [UniParc]FASTAAdd to basket
Also known as: DUSP6-ALT

The sequence of this isoform differs from the canonical sequence as follows:
     134-279: Missing.

Show »
Length:235
Mass (Da):26,468
Checksum:i24E84490A10D2D87
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06994377F → I in HH19. 1 PublicationCorresponds to variant rs587776978dbSNPEnsembl.1
Natural variantiVAR_015113114V → L.3 PublicationsCorresponds to variant rs2279574dbSNPEnsembl.1
Natural variantiVAR_051750144S → A.Corresponds to variant rs770087dbSNPEnsembl.1
Natural variantiVAR_069944182S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. 1 PublicationCorresponds to variant rs139318648dbSNPEnsembl.1
Natural variantiVAR_069945189N → S in HH19. 1 PublicationCorresponds to variant rs143946794dbSNPEnsembl.1
Natural variantiVAR_051751313N → I.Corresponds to variant rs12828557dbSNPEnsembl.1
Natural variantiVAR_069946346T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. 1 PublicationCorresponds to variant rs146089505dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005137134 – 279Missing in isoform 2. 1 PublicationAdd BLAST146

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93920 mRNA. Translation: CAA63813.1.
AB013601 Genomic DNA. Translation: BAA31968.1.
AB013382 mRNA. Translation: BAA34369.1.
AB013602 mRNA. Translation: BAA31969.1.
BT006895 mRNA. Translation: AAP35541.1.
BC003143 mRNA. Translation: AAH03143.1.
BC003562 mRNA. Translation: AAH03562.1.
BC005047 mRNA. Translation: AAH05047.1.
BC037236 mRNA. Translation: AAH37236.1.
CCDSiCCDS9033.1. [Q16828-1]
CCDS9034.1. [Q16828-2]
RefSeqiNP_001937.2. NM_001946.3. [Q16828-1]
NP_073143.2. NM_022652.3. [Q16828-2]
UniGeneiHs.298654.
Hs.718640.

Genome annotation databases

EnsembliENST00000279488; ENSP00000279488; ENSG00000139318. [Q16828-1]
ENST00000308385; ENSP00000307835; ENSG00000139318. [Q16828-2]
GeneIDi1848.
KEGGihsa:1848.
UCSCiuc001tay.5. human. [Q16828-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93920 mRNA. Translation: CAA63813.1.
AB013601 Genomic DNA. Translation: BAA31968.1.
AB013382 mRNA. Translation: BAA34369.1.
AB013602 mRNA. Translation: BAA31969.1.
BT006895 mRNA. Translation: AAP35541.1.
BC003143 mRNA. Translation: AAH03143.1.
BC003562 mRNA. Translation: AAH03562.1.
BC005047 mRNA. Translation: AAH05047.1.
BC037236 mRNA. Translation: AAH37236.1.
CCDSiCCDS9033.1. [Q16828-1]
CCDS9034.1. [Q16828-2]
RefSeqiNP_001937.2. NM_001946.3. [Q16828-1]
NP_073143.2. NM_022652.3. [Q16828-2]
UniGeneiHs.298654.
Hs.718640.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HZMNMR-A1-154[»]
1MKPX-ray2.35A205-347[»]
ProteinModelPortaliQ16828.
SMRiQ16828.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108181. 10 interactors.
IntActiQ16828. 6 interactors.
MINTiMINT-1442837.
STRINGi9606.ENSP00000279488.

Chemistry databases

BindingDBiQ16828.
ChEMBLiCHEMBL1250381.

PTM databases

DEPODiQ16828.
iPTMnetiQ16828.
PhosphoSitePlusiQ16828.

Polymorphism and mutation databases

BioMutaiDUSP6.
DMDMi108860971.

Proteomic databases

MaxQBiQ16828.
PaxDbiQ16828.
PeptideAtlasiQ16828.
PRIDEiQ16828.

Protocols and materials databases

DNASUi1848.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000279488; ENSP00000279488; ENSG00000139318. [Q16828-1]
ENST00000308385; ENSP00000307835; ENSG00000139318. [Q16828-2]
GeneIDi1848.
KEGGihsa:1848.
UCSCiuc001tay.5. human. [Q16828-1]

Organism-specific databases

CTDi1848.
DisGeNETi1848.
GeneCardsiDUSP6.
HGNCiHGNC:3072. DUSP6.
HPAiCAB017566.
HPA053188.
MalaCardsiDUSP6.
MIMi602748. gene.
615269. phenotype.
neXtProtiNX_Q16828.
OpenTargetsiENSG00000139318.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA27529.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1717. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00760000118902.
HOGENOMiHOG000294079.
HOVERGENiHBG007347.
InParanoidiQ16828.
KOiK04459.
OMAiRDWNENT.
OrthoDBiEOG091G0249.
PhylomeDBiQ16828.
TreeFamiTF105122.

Enzyme and pathway databases

BioCyciZFISH:HS06607-MONOMER.
BRENDAi3.1.3.16. 2681.
3.1.3.48. 2681.
ReactomeiR-HSA-112409. RAF-independent MAPK1/3 activation.
R-HSA-202670. ERKs are inactivated.
R-HSA-5675221. Negative regulation of MAPK pathway.
SignaLinkiQ16828.
SIGNORiQ16828.

Miscellaneous databases

ChiTaRSiDUSP6. human.
EvolutionaryTraceiQ16828.
GeneWikiiDUSP6.
GenomeRNAii1848.
PROiQ16828.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139318.
CleanExiHS_DUSP6.
ExpressionAtlasiQ16828. baseline and differential.
GenevisibleiQ16828. HS.

Family and domain databases

CDDicd00127. DSPc. 1 hit.
Gene3Di3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR008343. MKP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR001763. Rhodanese-like_dom.
IPR000387. TYR_PHOSPHATASE_dom.
IPR020422. TYR_PHOSPHATASE_DUAL_dom.
[Graphical view]
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiPF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PIRSFiPIRSF000939. MAPK_Ptase. 1 hit.
PRINTSiPR01764. MAPKPHPHTASE.
SMARTiSM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF52821. SSF52821. 1 hit.
PROSITEiPS50206. RHODANESE_3. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDUS6_HUMAN
AccessioniPrimary (citable) accession number: Q16828
Secondary accession number(s): O75109, Q53Y75, Q9BSH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2006
Last modified: November 30, 2016
This is version 171 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.