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Q16828

- DUS6_HUMAN

UniProt

Q16828 - DUS6_HUMAN

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
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 2 (30 May 2006)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiQ16828.
    BgeeiQ16828.
    CleanExiHS_DUSP6.
    GenevestigatoriQ16828.

    Organism-specific databases

    HPAiCAB017566.

    Interactioni

    Protein-protein interaction databases

    BioGridi108181. 10 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.
    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

    MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI    50
    ESAINVAIPG IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE 100
    SSSDWNENTG GESVLGLLLK KLKDEGCRAF YLEGGFSKFQ AEFSLHCETN 150
    LDGSCSSSSP PLPVLGLGGL RISSDSSSDI ESDLDRDPNS ATDSDGSPLS 200
    NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT PNLPNLFENA 250
    GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS 300
    VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS 350
    SPCDNRVPAQ QLYFTTPSNQ NVYQVDSLQS T 381
    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. 10 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.
    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

    ArrayExpressi Q16828.
    Bgeei Q16828.
    CleanExi HS_DUSP6.
    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

    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 1, 2014
    This is version 150 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