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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.

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei293 – 2931Phosphocysteine intermediate

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

BRENDAi3.1.3.16. 2681.
3.1.3.48. 2681.
ReactomeiREACT_12436. ERKs are inactivated.
SignaLinkiQ16828.

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
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3072. DUSP6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Ensembl
  • 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).

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771F → I in HH19. 1 Publication
VAR_069943
Natural varianti182 – 1821S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. 1 Publication
VAR_069944
Natural varianti189 – 1891N → S in HH19. 1 Publication
Corresponds to variant rs143946794 [ dbSNP | Ensembl ].
VAR_069945
Natural varianti346 – 3461T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. 1 Publication
Corresponds to variant rs146089505 [ dbSNP | Ensembl ].
VAR_069946

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiDUSP6.
DMDMi108860971.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 381381Dual specificity protein phosphatase 6PRO_0000094804Add
BLAST

Proteomic databases

MaxQBiQ16828.
PaxDbiQ16828.
PRIDEiQ16828.

PTM databases

DEPODiQ16828.
PhosphoSiteiQ16828.

Expressioni

Gene expression databases

BgeeiQ16828.
CleanExiHS_DUSP6.
ExpressionAtlasiQ16828. baseline and differential.
GenevisibleiQ16828. HS.

Organism-specific databases

HPAiCAB017566.

Interactioni

Protein-protein interaction databases

BioGridi108181. 9 interactions.
IntActiQ16828. 6 interactions.
MINTiMINT-1442837.
STRINGi9606.ENSP00000279488.

Structurei

Secondary structure

1
381
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 126Combined sources
Beta strandi15 – 184Combined sources
Helixi23 – 297Combined sources
Beta strandi31 – 333Combined sources
Beta strandi35 – 373Combined sources
Helixi43 – 486Combined sources
Beta strandi50 – 523Combined sources
Helixi61 – 644Combined sources
Turni73 – 764Combined sources
Helixi81 – 888Combined sources
Beta strandi95 – 973Combined sources
Beta strandi101 – 1055Combined sources
Helixi114 – 12411Combined sources
Helixi136 – 1438Combined sources
Beta strandi149 – 1524Combined sources
Beta strandi208 – 2114Combined sources
Beta strandi214 – 2174Combined sources
Helixi225 – 2306Combined sources
Beta strandi233 – 2386Combined sources
Beta strandi246 – 2505Combined sources
Beta strandi253 – 2575Combined sources
Helixi269 – 2713Combined sources
Helixi272 – 28413Combined sources
Beta strandi288 – 2925Combined sources
Helixi298 – 31215Combined sources
Helixi316 – 32611Combined sources
Helixi337 – 3459Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HZMNMR-A1-154[»]
1MKPX-ray2.35A205-347[»]
ProteinModelPortaliQ16828.
SMRiQ16828. Positions 1-154, 205-347.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16828.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 148119RhodanesePROSITE-ProRule annotationAdd
BLAST
Domaini206 – 381176Tyrosine-protein phosphataseAdd
BLAST

Sequence similaritiesi

Contains 1 rhodanese domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG2453.
GeneTreeiENSGT00760000118902.
HOGENOMiHOG000294079.
HOVERGENiHBG007347.
InParanoidiQ16828.
KOiK04459.
OMAiRDWNENT.
PhylomeDBiQ16828.
TreeFamiTF105122.

Family and domain databases

Gene3Di3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR008343. MKP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR001763. Rhodanese-like_dom.
IPR000387. Tyr/Dual-sp_Pase.
[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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771F → I in HH19. 1 Publication
VAR_069943
Natural varianti114 – 1141V → L.3 Publications
Corresponds to variant rs2279574 [ dbSNP | Ensembl ].
VAR_015113
Natural varianti144 – 1441S → A.
Corresponds to variant rs770087 [ dbSNP | Ensembl ].
VAR_051750
Natural varianti182 – 1821S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. 1 Publication
VAR_069944
Natural varianti189 – 1891N → S in HH19. 1 Publication
Corresponds to variant rs143946794 [ dbSNP | Ensembl ].
VAR_069945
Natural varianti313 – 3131N → I.
Corresponds to variant rs12828557 [ dbSNP | Ensembl ].
VAR_051751
Natural varianti346 – 3461T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. 1 Publication
Corresponds to variant rs146089505 [ dbSNP | Ensembl ].
VAR_069946

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei134 – 279146Missing in isoform 2. 1 PublicationVSP_005137Add
BLAST

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.
ENST00000308385; ENSP00000307835; ENSG00000139318. [Q16828-2]
GeneIDi1848.
KEGGihsa:1848.
UCSCiuc001tay.3. human. [Q16828-1]
uc001taz.3. human. [Q16828-2]

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
EntryMethodResolution (Å)ChainPositionsPDBsum
1HZMNMR-A1-154[»]
1MKPX-ray2.35A205-347[»]
ProteinModelPortaliQ16828.
SMRiQ16828. Positions 1-154, 205-347.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108181. 9 interactions.
IntActiQ16828. 6 interactions.
MINTiMINT-1442837.
STRINGi9606.ENSP00000279488.

Chemistry

BindingDBiQ16828.
ChEMBLiCHEMBL1250381.

PTM databases

DEPODiQ16828.
PhosphoSiteiQ16828.

Polymorphism and mutation databases

BioMutaiDUSP6.
DMDMi108860971.

Proteomic databases

MaxQBiQ16828.
PaxDbiQ16828.
PRIDEiQ16828.

Protocols and materials databases

DNASUi1848.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000279488; ENSP00000279488; ENSG00000139318.
ENST00000308385; ENSP00000307835; ENSG00000139318. [Q16828-2]
GeneIDi1848.
KEGGihsa:1848.
UCSCiuc001tay.3. human. [Q16828-1]
uc001taz.3. human. [Q16828-2]

Organism-specific databases

CTDi1848.
GeneCardsiGC12M089741.
HGNCiHGNC:3072. DUSP6.
HPAiCAB017566.
MIMi602748. gene.
615269. phenotype.
neXtProtiNX_Q16828.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA27529.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2453.
GeneTreeiENSGT00760000118902.
HOGENOMiHOG000294079.
HOVERGENiHBG007347.
InParanoidiQ16828.
KOiK04459.
OMAiRDWNENT.
PhylomeDBiQ16828.
TreeFamiTF105122.

Enzyme and pathway databases

BRENDAi3.1.3.16. 2681.
3.1.3.48. 2681.
ReactomeiREACT_12436. ERKs are inactivated.
SignaLinkiQ16828.

Miscellaneous databases

ChiTaRSiDUSP6. human.
EvolutionaryTraceiQ16828.
GeneWikiiDUSP6.
GenomeRNAii1848.
NextBioi7569.
PROiQ16828.
SOURCEiSearch...

Gene expression databases

BgeeiQ16828.
CleanExiHS_DUSP6.
ExpressionAtlasiQ16828. baseline and differential.
GenevisibleiQ16828. HS.

Family and domain databases

Gene3Di3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR008343. MKP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR001763. Rhodanese-like_dom.
IPR000387. Tyr/Dual-sp_Pase.
[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...

Publicationsi

« Hide 'large scale' publications
  1. "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase."
    Groom L.A., Sneddon A.A., Alessi D.R., Dowd S., Keyse S.M.
    EMBO J. 15:3621-3632(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-114.
    Tissue: Foreskin.
  2. "Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer."
    Furukawa T., Yatsuoka T., Youssef E.M., Abe T., Yokoyama T., Fukushige S., Soeda E., Hoshi M., Hayashi Y., Sunamura M., Kobari M., Horii A.
    Cytogenet. Cell Genet. 82:156-159(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANT LEU-114.
    Tissue: Liver.
  3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-114.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Colon, Kidney, Skin and Stomach.
  5. "Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation."
    Stewart A.E., Dowd S., Keyse S.M., McDonald N.Q.
    Nat. Struct. Biol. 6:174-181(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 204-347.
  6. Cited for: VARIANTS HH19 ILE-77; PHE-182; SER-189 AND MET-346.

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: July 22, 2015
This is version 158 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

External Data

Dasty 3

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 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.