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FLASH GENE
Symbol DUSP4 contributors: mct/npt/pgu - updated : 31-08-2018
HGNC name dual specificity phosphatase 4
HGNC id 3070
Location 8p12      Physical location : 29.193.616 - 29.208.185
Synonym name
  • vaccinia virus phosphatase VH1-like 2
  • mitogen activated protein kinase (MAPK) phosphatase 4
  • MAP kinase phosphatase 2
  • dual specificity protein phosphatase hVH2
  • serine/threonine specific protein phosphatase
    • Synonym symbol(s) HVH2, MKP2, TYP, MKP-2
    EC.number 3.1.3.48, 3.1.3.16
    DNA
    TYPE functioning gene
    STRUCTURE 14.57 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map pter - D8S1771 - DUSP4 - D8S505 - cen
    Authors SCW8-3 (96)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2498 - 394 - 2010 19843478
  • MKP-2-L
  • able to reverse serum-induced ERK activation or significantly inhibit endothelial cell proliferation
    • 5 - 3404 - 303 - 2010 19843478
  • MKP-2-S
  • lacking the MAP kinase binding site but retaining the phosphatase catalytic domain
  • lack of a kinase interacting motif (KIM), and MKP-2-S did not bind to JNK or ERK
  • retained its ability to deactivate JNK in a similar manner as MKP-2-L and was an effective inhibitor of LPS-stimulated COX-2 induction
  • unlike MKP-2-L, MKP-2-S was unable to reverse serum-induced ERK activation or significantly inhibit endothelial cell proliferation
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two N terminal CH2 domains
  • an extended active site sequence motif conserved in dual specificity phosphatases
    • HOMOLOGY
    Homologene
    FAMILY
  • protein-tyrosine phosphatase family
  • non-receptor class dual specificity subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text
  • nuclear located enzyme
    • basic FUNCTION
  • involved, with DUSP2 in stimulus-specific, and phosphatase-specific mechanism of MAPK1 regulation in the nucleus
  • part of a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate
  • involved in negative feedback control of EGFR signaling
  • having functions to inactivate the ERK and JNK MAP kinase signalling pathways
  • critical non-redundant role in regulating cell cycle progression and apoptosis
  • required for cardiac fibroblast and macrophage proliferation
  • essential role in protecting cellular integrity
  • plays potentially opposing roles in different types of cancer depending on which kinase, ERK or JNK, is being preferentially regulated in that cell type
  • MAP kinase-induced DUSP member that is dynamically expressed during thymocyte differentiation
  • DUSP4 causes cardiac dysfunction and may contribute to the development of LMNA cardiomyopathy
  • attenuates ERK signaling and reduces cell viability, suggesting that the novel crosstalk between NFKB1 and MAPK pathways contributes to cell survival
  • DUSP4 is crucial for neuronal differentiation and functions in the neurogenesis of embryonic stem cells (ESCs)
  • regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation
  • is important for helper T cell development, and there is a DUSP4-mediated regulation of STAT5B protein stability
  • is a critical regulator of the growth and invasion of triple-negative breast cancer cells
  • is crucial in regulating corticosteroid sensitivity
  • is a key contributor to the pathogenesis of LMNA cardiomyopathy
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • bound ERK and to a lesser extent JNK
  • DUSP4 suppresses CD4(+) T-cell proliferation through novel regulations in STAT5B phosphorylation and IL2 signaling
  • TNF caused a significant suppression of a dual specificity phosphatase, DUSP4, that regulates ERK1/2 activation
  • DUSP4 regulates STAT5B protein stability and helper T cell polarization
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in senescent fibroblasts, compared to their young counterparts
    tumoral somatic mutation     gain of function
    activating KRAS mutations is significantly correlated to an upregulation of 13 genes among them DUSP4, a MAP-kinase phosphatase, and SMYD3 in colorectal cancer
    tumoral     --low  
    through activation of the MAPK signaling pathway is responsible for progression of Colorectal cancer
    tumoral   deletion    
    in approximately 50 p100 of breast cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • low DUSP4 expression levels predict recurrence and mortality in Triple-negative breast cancer (TNBC) patients independently from known clinical and molecular predictors
    • Therapy target
    SystemTypeDisorderPubmed
    respiratorylung 
    might be a novel therapeutic target in severe asthma
    ANIMAL & CELL MODELS