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UniProtKB - Q16828 (DUS6_HUMAN)

Protein

Dual specificity protein phosphatase 6

Gene

DUSP6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Also important for dephosphorylation of MAPK1/3 in local wound tissue, which further contributes to resolution of acute pain (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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000139318.7
HGNCiHGNC:3072 DUSP6
MIMi602748 gene
neXtProtiNX_Q16828

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs587776978EnsemblClinVar.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 dbSNP:rs139318648EnsemblClinVar.1
Natural variantiVAR_069945189N → S in HH19. 1 PublicationCorresponds to variant dbSNP:rs143946794EnsemblClinVar.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 dbSNP:rs146089505EnsemblClinVar.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

EPDiQ16828
MaxQBiQ16828
PaxDbiQ16828
PeptideAtlasiQ16828
PRIDEiQ16828
ProteomicsDBi61089
61090 [Q16828-2]

PTM databases

DEPODiQ16828
iPTMnetiQ16828
PhosphoSitePlusiQ16828

Expressioni

Gene expression databases

BgeeiENSG00000139318 Expressed in 242 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_DUSP6
ExpressionAtlasiQ16828 baseline and differential
GenevisibleiQ16828 HS

Organism-specific databases

HPAiCAB017566
HPA053188

Interactioni

Protein-protein interaction databases

BioGridi108181, 60 interactors
ELMiQ16828
IntActiQ16828, 6 interactors
MINTiQ16828
STRINGi9606.ENSP00000279488

Chemistry databases

BindingDBiQ16828

Structurei

Secondary structure

1381
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.Curated

Phylogenomic databases

eggNOGiKOG1717 Eukaryota
COG2453 LUCA
GeneTreeiENSGT00760000118902
HOGENOMiHOG000294079
HOVERGENiHBG007347
InParanoidiQ16828
KOiK21946
OMAiLLVMDCR
OrthoDBiEOG091G0249
PhylomeDBiQ16828
TreeFamiTF105122

Family and domain databases

CDDicd00127 DSPc, 1 hit
Gene3Di3.40.250.10, 1 hit
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR000340 Dual-sp_phosphatase_cat-dom
IPR024950 DUSP
IPR008343 MKP
IPR029021 Prot-tyrosine_phosphatase-like
IPR001763 Rhodanese-like_dom
IPR036873 Rhodanese-like_dom_sf
IPR000387 TYR_PHOSPHATASE_dom
IPR020422 TYR_PHOSPHATASE_DUAL_dom
PANTHERiPTHR10159 PTHR10159, 1 hit
PfamiView protein in Pfam
PF00782 DSPc, 1 hit
PF00581 Rhodanese, 1 hit
PIRSFiPIRSF000939 MAPK_Ptase, 1 hit
PRINTSiPR01764 MAPKPHPHTASE
SMARTiView protein in SMART
SM00195 DSPc, 1 hit
SM00450 RHOD, 1 hit
SUPFAMiSSF52799 SSF52799, 1 hit
SSF52821 SSF52821, 1 hit
PROSITEiView protein in PROSITE
PS50206 RHODANESE_3, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50054 TYR_PHOSPHATASE_DUAL, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VW29F8VW29_HUMAN
Dual-specificity protein phosphatas...
DUSP6
256Annotation score:
F8VZA4F8VZA4_HUMAN
Dual-specificity protein phosphatas...
DUSP6
117Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06994377F → I in HH19. 1 PublicationCorresponds to variant dbSNP:rs587776978EnsemblClinVar.1
Natural variantiVAR_015113114V → L3 PublicationsCorresponds to variant dbSNP:rs2279574Ensembl.1
Natural variantiVAR_051750144S → A. Corresponds to variant dbSNP:rs770087Ensembl.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 dbSNP:rs139318648EnsemblClinVar.1
Natural variantiVAR_069945189N → S in HH19. 1 PublicationCorresponds to variant dbSNP:rs143946794EnsemblClinVar.1
Natural variantiVAR_051751313N → I. Corresponds to variant dbSNP:rs12828557Ensembl.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 dbSNP:rs146089505EnsemblClinVar.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

Similar proteinsi

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, 60 interactors
ELMiQ16828
IntActiQ16828, 6 interactors
MINTiQ16828
STRINGi9606.ENSP00000279488

Chemistry databases

BindingDBiQ16828
ChEMBLiCHEMBL1250381

PTM databases

DEPODiQ16828
iPTMnetiQ16828
PhosphoSitePlusiQ16828

Polymorphism and mutation databases

BioMutaiDUSP6
DMDMi108860971

Proteomic databases

EPDiQ16828
MaxQBiQ16828
PaxDbiQ16828
PeptideAtlasiQ16828
PRIDEiQ16828
ProteomicsDBi61089
61090 [Q16828-2]

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
EuPathDBiHostDB:ENSG00000139318.7
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
KOiK21946
OMAiLLVMDCR
OrthoDBiEOG091G0249
PhylomeDBiQ16828
TreeFamiTF105122

Enzyme and pathway databases

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
PROiPR:Q16828
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139318 Expressed in 242 organ(s), highest expression level in pigmented layer of retina
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
InterProiView protein in InterPro
IPR000340 Dual-sp_phosphatase_cat-dom
IPR024950 DUSP
IPR008343 MKP
IPR029021 Prot-tyrosine_phosphatase-like
IPR001763 Rhodanese-like_dom
IPR036873 Rhodanese-like_dom_sf
IPR000387 TYR_PHOSPHATASE_dom
IPR020422 TYR_PHOSPHATASE_DUAL_dom
PANTHERiPTHR10159 PTHR10159, 1 hit
PfamiView protein in Pfam
PF00782 DSPc, 1 hit
PF00581 Rhodanese, 1 hit
PIRSFiPIRSF000939 MAPK_Ptase, 1 hit
PRINTSiPR01764 MAPKPHPHTASE
SMARTiView protein in SMART
SM00195 DSPc, 1 hit
SM00450 RHOD, 1 hit
SUPFAMiSSF52799 SSF52799, 1 hit
SSF52821 SSF52821, 1 hit
PROSITEiView protein in PROSITE
PS50206 RHODANESE_3, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50054 TYR_PHOSPHATASE_DUAL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDUS6_HUMAN
AccessioniPrimary (citable) accession number: Q16828
Secondary accession number(s): O75109, Q53Y75, Q9BSH6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2006
Last modified: September 12, 2018
This is version 182 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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