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    DUSP3 dual specificity phosphatase 3 [ Homo sapiens (human) ]

    Gene ID: 1845, updated on 13-Aug-2016
    Official Symbol
    DUSP3provided by HGNC
    Official Full Name
    dual specificity phosphatase 3provided by HGNC
    Primary source
    HGNC:HGNC:3069
    See related
    Ensembl:ENSG00000108861 HPRD:02553; MIM:600183; Vega:OTTHUMG00000180889
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    VHR
    Summary
    The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    17q21
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 17 NC_000017.11 (43766121..43779000, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (41843489..41856368, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene Wolf-Hirschhorn syndrome candidate 1-like 2, pseudogene Neighboring gene sclerostin Neighboring gene chromosome 17 open reading frame 105 Neighboring gene membrane palmitoylated protein 3 Neighboring gene uncharacterized LOC107984979

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
      Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
    • ERK/MAPK targets, organism-specific biosystem (from REACTOME)
      ERK/MAPK targets, organism-specific biosystemERK/MAPK kinases have a number of targets within the nucleus, usually transcription factors or other kinases. The best known targets, ELK1, ETS1, ATF2, MITF, MAPKAPK2, MSK1, RSK1/2/3 and MEF2 are ann...
    • ERKs are inactivated, organism-specific biosystem (from REACTOME)
      ERKs are inactivated, organism-specific biosystemMAP Kinases are inactivated by a family of protein named MAP Kinase Phosphatases (MKPs). They act through dephosphorylation of threonine and/or tyrosine residues within the signature sequence -pTXpY-...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • MAP kinase activation in TLR cascade, organism-specific biosystem (from REACTOME)
      MAP kinase activation in TLR cascade, organism-specific biosystemThe mitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascad...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK targets/ Nuclear events mediated by MAP kinases, organism-specific biosystem (from REACTOME)
      MAPK targets/ Nuclear events mediated by MAP kinases, organism-specific biosystemMAPKs are protein kinases that, once activated, phosphorylate their specific cytosolic or nuclear substrates at serine and/or threonine residues. Such phosphorylation events can either positively or ...
    • MyD88 cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88 cascade initiated on plasma membrane, organism-specific biosystemMammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of...
    • MyD88 dependent cascade initiated on endosome, organism-specific biosystem (from REACTOME)
      MyD88 dependent cascade initiated on endosome, organism-specific biosystemUpon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I ...
    • MyD88-independent TLR3/TLR4 cascade, organism-specific biosystem (from REACTOME)
      MyD88-independent TLR3/TLR4 cascade, organism-specific biosystemMyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from ...
    • MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystemThe first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also b...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Nuclear Events (kinase and transcription factor activation), organism-specific biosystem (from REACTOME)
      Nuclear Events (kinase and transcription factor activation), organism-specific biosystemAn important function of the kinase cascade triggered by neurotrophins is to induce the phosphorylation and activation of transcription factors in the nucleus to initiate new programs of gene express...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystem (from REACTOME)
      TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystemTRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.
    • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
      TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
    • Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystemLittle is known about TLR10 ligands. It has been established that the receptor homodimerizes upon binding and signals in an MyD88-dependent manner (Hasan U et al 2005; Nyman T et al 2008). It may als...
    • Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystemTLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at le...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
    • Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystemTLR5 is the receptor for flagellin, the protein that forms bacterial flagella. Unlike most other Pathogen-Associated Molecular Patterns (PAMPs), flagellin does not undergo any posttranslational modif...
    • Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystemRNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich...
    • Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystemCpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated....
    • Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystemTLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial...
    • Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystemTLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recog...
    • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
      Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
     
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    immunological synapse IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    dual specificity protein phosphatase 3
    Names
    dual specificity protein phosphatase VHR
    serine/threonine specific protein phosphatase
    vaccinia H1-related phosphatase
    vaccinia virus phosphatase VH1-related
    NP_004081.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_004090.3NP_004081.1  dual specificity protein phosphatase 3

      See identical proteins and their annotated locations for NP_004081.1

      Status: REVIEWED

      Source sequence(s)
      AC055813, AK055834, AK129822, BC002682, BQ575811, BQ652984, DA075379, DA104250, DA167802, DB171573
      Consensus CDS
      CCDS11469.1
      UniProtKB/Swiss-Prot
      P51452
      Related
      ENSP00000226004, OTTHUMP00000265597, ENST00000226004, OTTHUMT00000453503
      Conserved Domains (1) summary
      cd00127
      Location:29174
      DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p7 Primary Assembly

      Range
      43766121..43779000 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018928.2 Alternate CHM1_1.1

      Range
      42079099..42091978 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)