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Q16828 (DUS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:DUSP6
Synonyms:MKP3, PYST1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length381 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inactivates MAP kinases. Has a specificity for the ERK family.

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

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

Subcellular location

Cytoplasm.

Involvement in disease

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).
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 (Ref.6). Ref.6

Sequence similarities

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

Contains 1 rhodanese domain.

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Hypogonadotropic hypogonadism
Kallmann syndrome
   Molecular functionHydrolase
Protein phosphatase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

cell differentiation

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral pattern formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

inactivation of MAPK activity

Inferred from direct assay Ref.1. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

negative regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 18771677. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-tyrosine dephosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 10846176. Source: UniProtKB

regulation of endodermal cell fate specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of fibroblast growth factor receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of heart growth

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to drug

Inferred from electronic annotation. Source: Ensembl

response to nitrosative stress

Inferred from expression pattern PubMed 10846176. Source: UniProtKB

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1PubMed 9788880. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionMAP kinase tyrosine/serine/threonine phosphatase activity

Inferred from direct assay Ref.1. Source: UniProtKB

protein tyrosine phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16828-1)

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.
Isoform 2 (identifier: Q16828-2)

Also known as: DUSP6-ALT;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 381381Dual specificity protein phosphatase 6
PRO_0000094804

Regions

Domain30 – 148119Rhodanese
Domain206 – 381176Tyrosine-protein phosphatase

Sites

Active site2931Phosphocysteine intermediate

Natural variations

Alternative sequence134 – 279146Missing in isoform 2.
VSP_005137
Natural variant771F → I in HH19. Ref.6
VAR_069943
Natural variant1141V → L. Ref.1 Ref.2 Ref.3
Corresponds to variant rs2279574 [ dbSNP | Ensembl ].
VAR_015113
Natural variant1441S → A.
Corresponds to variant rs770087 [ dbSNP | Ensembl ].
VAR_051750
Natural variant1821S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. Ref.6
VAR_069944
Natural variant1891N → S in HH19. Ref.6
Corresponds to variant rs143946794 [ dbSNP | Ensembl ].
VAR_069945
Natural variant3131N → I.
Corresponds to variant rs12828557 [ dbSNP | Ensembl ].
VAR_051751
Natural variant3461T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. Ref.6
Corresponds to variant rs146089505 [ dbSNP | Ensembl ].
VAR_069946

Secondary structure

...................................................... 381
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: 386612227F5D3B2A

FASTA38142,320
        10         20         30         40         50         60 
MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI ESAINVAIPG 

        70         80         90        100        110        120 
IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE SSSDWNENTG GESVLGLLLK 

       130        140        150        160        170        180 
KLKDEGCRAF YLEGGFSKFQ AEFSLHCETN LDGSCSSSSP PLPVLGLGGL RISSDSSSDI 

       190        200        210        220        230        240 
ESDLDRDPNS ATDSDGSPLS NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT 

       250        260        270        280        290        300 
PNLPNLFENA GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS 

       310        320        330        340        350        360 
VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS SPCDNRVPAQ 

       370        380 
QLYFTTPSNQ NVYQVDSLQS T 

« Hide

Isoform 2 (DUSP6-ALT) [UniParc].

Checksum: 24E84490A10D2D87
Show »

FASTA23526,468

References

« Hide 'large scale' references
[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]"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., Kumanov P. expand/collapse author list , Young J., Yialamas M.A., Hall J.E., Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., Pitteloud N.
Am. J. Hum. Genet. 92:725-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HH19 ILE-77; PHE-182; SER-189 AND MET-346.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS9033.1. [Q16828-1]
CCDS9034.1. [Q16828-2]
RefSeqNP_001937.2. NM_001946.3. [Q16828-1]
NP_073143.2. NM_022652.3. [Q16828-2]
UniGeneHs.298654.
Hs.718640.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HZMNMR-A1-154[»]
1MKPX-ray2.35A205-347[»]
ProteinModelPortalQ16828.
SMRQ16828. Positions 1-154, 205-347.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108181. 10 interactions.
IntActQ16828. 6 interactions.
MINTMINT-1442837.
STRING9606.ENSP00000279488.

Chemistry

BindingDBQ16828.
ChEMBLCHEMBL1250381.

PTM databases

PhosphoSiteQ16828.

Polymorphism databases

DMDM108860971.

Proteomic databases

MaxQBQ16828.
PaxDbQ16828.
PRIDEQ16828.

Protocols and materials databases

DNASU1848.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000279488; ENSP00000279488; ENSG00000139318. [Q16828-1]
ENST00000308385; ENSP00000307835; ENSG00000139318. [Q16828-2]
GeneID1848.
KEGGhsa:1848.
UCSCuc001tay.3. human. [Q16828-1]
uc001taz.3. human. [Q16828-2]

Organism-specific databases

CTD1848.
GeneCardsGC12M089741.
HGNCHGNC:3072. DUSP6.
HPACAB017566.
MIM602748. gene.
615269. phenotype.
neXtProtNX_Q16828.
Orphanet478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBPA27529.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2453.
HOGENOMHOG000294079.
HOVERGENHBG007347.
InParanoidQ16828.
KOK04459.
OMASEWNENT.
PhylomeDBQ16828.
TreeFamTF105122.

Enzyme and pathway databases

BRENDA3.1.3.48. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkQ16828.

Gene expression databases

ArrayExpressQ16828.
BgeeQ16828.
CleanExHS_DUSP6.
GenevestigatorQ16828.

Family and domain databases

Gene3D3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProIPR000340. 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]
PANTHERPTHR10159. PTHR10159. 1 hit.
PfamPF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PIRSFPIRSF000939. MAPK_Ptase. 1 hit.
PRINTSPR01764. MAPKPHPHTASE.
SMARTSM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMSSF52799. SSF52799. 1 hit.
SSF52821. SSF52821. 1 hit.
PROSITEPS50206. RHODANESE_3. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDUSP6. human.
EvolutionaryTraceQ16828.
GeneWikiDUSP6.
GenomeRNAi1848.
NextBio7569.
PROQ16828.
SOURCESearch...

Entry information

Entry nameDUS6_HUMAN
AccessionPrimary (citable) accession number: Q16828
Secondary accession number(s): O75109, Q53Y75, Q9BSH6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM