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Q16828

- DUS6_HUMAN

UniProt

Q16828 - DUS6_HUMAN

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Protein

Dual specificity protein phosphatase 6

Gene

DUSP6

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. MAP kinase tyrosine/serine/threonine phosphatase activity Source: UniProtKB
  2. protein tyrosine phosphatase activity Source: UniProtKB-EC

GO - Biological processi

  1. cell differentiation Source: Ensembl
  2. dorsal/ventral pattern formation Source: RefGenome
  3. inactivation of MAPK activity Source: UniProtKB
  4. innate immune response Source: Reactome
  5. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  6. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  7. negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  8. neurotrophin TRK receptor signaling pathway Source: Reactome
  9. peptidyl-tyrosine dephosphorylation Source: UniProtKB
  10. positive regulation of apoptotic process Source: UniProtKB
  11. regulation of endodermal cell fate specification Source: RefGenome
  12. regulation of fibroblast growth factor receptor signaling pathway Source: RefGenome
  13. regulation of heart growth Source: RefGenome
  14. response to drug Source: Ensembl
  15. response to nitrosative stress Source: UniProtKB
  16. response to organic cyclic compound Source: Ensembl
  17. stress-activated MAPK cascade Source: Reactome
  18. toll-like receptor 10 signaling pathway Source: Reactome
  19. toll-like receptor 2 signaling pathway Source: Reactome
  20. toll-like receptor 3 signaling pathway Source: Reactome
  21. toll-like receptor 4 signaling pathway Source: Reactome
  22. toll-like receptor 5 signaling pathway Source: Reactome
  23. toll-like receptor 9 signaling pathway Source: Reactome
  24. toll-like receptor signaling pathway Source: Reactome
  25. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  26. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  27. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

BRENDAi3.1.3.48. 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: Chromosome 12

Organism-specific databases

HGNCiHGNC:3072. DUSP6.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 19 with or without anosmia (HH19) [MIM:615269]: A 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).1 Publication
Note: 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
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.

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

PhosphoSiteiQ16828.

Expressioni

Gene expression databases

BgeeiQ16828.
CleanExiHS_DUSP6.
ExpressionAtlasiQ16828. baseline and differential.
GenevestigatoriQ16828.

Organism-specific databases

HPAiCAB017566.

Interactioni

Protein-protein interaction databases

BioGridi108181. 11 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 – 126
Beta strandi15 – 184
Helixi23 – 297
Beta strandi31 – 333
Beta strandi35 – 373
Helixi43 – 486
Beta strandi50 – 523
Helixi61 – 644
Turni73 – 764
Helixi81 – 888
Beta strandi95 – 973
Beta strandi101 – 1055
Helixi114 – 12411
Helixi136 – 1438
Beta strandi149 – 1524
Beta strandi208 – 2114
Beta strandi214 – 2174
Helixi225 – 2306
Beta strandi233 – 2386
Beta strandi246 – 2505
Beta strandi253 – 2575
Helixi269 – 2713
Helixi272 – 28413
Beta strandi288 – 2925
Helixi298 – 31215
Helixi316 – 32611
Helixi337 – 3459

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.
OMAiSEWNENT.
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. Align

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:
EMBL
GenBank
DDBJ
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

GeneIDi1848.
KEGGihsa:1848.
UCSCiuc001tay.3. human. [Q16828-1]
uc001taz.3. human. [Q16828-2]

Polymorphism databases

DMDMi108860971.

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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS9033.1. [Q16828-1 ]
CCDS9034.1. [Q16828-2 ]
RefSeqi NP_001937.2. NM_001946.3. [Q16828-1 ]
NP_073143.2. NM_022652.3. [Q16828-2 ]
UniGenei Hs.298654.
Hs.718640.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HZM NMR - A 1-154 [» ]
1MKP X-ray 2.35 A 205-347 [» ]
ProteinModelPortali Q16828.
SMRi Q16828. Positions 1-154, 205-347.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108181. 11 interactions.
IntActi Q16828. 6 interactions.
MINTi MINT-1442837.
STRINGi 9606.ENSP00000279488.

Chemistry

BindingDBi Q16828.
ChEMBLi CHEMBL1250381.

PTM databases

PhosphoSitei Q16828.

Polymorphism databases

DMDMi 108860971.

Proteomic databases

MaxQBi Q16828.
PaxDbi Q16828.
PRIDEi Q16828.

Protocols and materials databases

DNASUi 1848.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 1848.
KEGGi hsa:1848.
UCSCi uc001tay.3. human. [Q16828-1 ]
uc001taz.3. human. [Q16828-2 ]

Organism-specific databases

CTDi 1848.
GeneCardsi GC12M089741.
HGNCi HGNC:3072. DUSP6.
HPAi CAB017566.
MIMi 602748. gene.
615269. phenotype.
neXtProti NX_Q16828.
Orphaneti 478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBi PA27529.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2453.
GeneTreei ENSGT00760000118902.
HOGENOMi HOG000294079.
HOVERGENi HBG007347.
InParanoidi Q16828.
KOi K04459.
OMAi SEWNENT.
PhylomeDBi Q16828.
TreeFami TF105122.

Enzyme and pathway databases

BRENDAi 3.1.3.48. 2681.
Reactomei REACT_12436. ERKs are inactivated.
SignaLinki Q16828.

Miscellaneous databases

ChiTaRSi DUSP6. human.
EvolutionaryTracei Q16828.
GeneWikii DUSP6.
GenomeRNAii 1848.
NextBioi 7569.
PROi Q16828.
SOURCEi Search...

Gene expression databases

Bgeei Q16828.
CleanExi HS_DUSP6.
ExpressionAtlasi Q16828. baseline and differential.
Genevestigatori Q16828.

Family and domain databases

Gene3Di 3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProi IPR000340. 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 ]
PANTHERi PTHR10159. PTHR10159. 1 hit.
Pfami PF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view ]
PIRSFi PIRSF000939. MAPK_Ptase. 1 hit.
PRINTSi PR01764. MAPKPHPHTASE.
SMARTi SM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view ]
SUPFAMi SSF52799. SSF52799. 1 hit.
SSF52821. SSF52821. 1 hit.
PROSITEi PS50206. RHODANESE_3. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 151 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