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FLASH GENE
Symbol MAP2K4 contributors: mct/npt - updated : 10-05-2014
HGNC name mitogen-activated protein kinase kinase 4
HGNC id 6844
Location 17p12      Physical location : 11.924.134 - 12.047.050
Synonym name
  • stress associated protein kinase 1 (SAPK-ERK kinase 1), see TSG17E
  • JNK activating kinase 1
  • MAPK/ERK kinase 4
  • dual specificity mitogen-activated protein kinase kinase 4
  • Synonym symbol(s) MEK4, MKK4, JNKK1, SERK1, SEK1, MAPKK4, PRKMK4, JNKK
    EC.number 2.7.11.24, 2.7.12.2, 2.7.1.-
    DNA
    TYPE functioning gene
    STRUCTURE 123.01 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3840 44.16 399 overexpressed in rhabdomyosarcoma 2009 1901224
    12 - 3873 - 410 - 2009 1901224
    13 splicing - - - - 2014 24487067
  • having a an additional exon in front of the substrate binding D-domain
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Endocrinepancreas    
    Lymphoid/Immunelymph node    
    Reproductivefemale systemovary  highly
    Urinarybladder    
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a docking site, a stretch of about 20 amino acids immediately on the C-terminal side of the MAPKK catalytic domain (Takekawa 2005)
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Map2k4
    homolog to C.elegans R03g5.2
    homolog to yeast S.cerevisiae PBS2
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP kinase kinase subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • may be involved in JNK cascade, protein amino acid phosphorylation, signal transduction
  • having serine/threonine kinase activity
  • playing a role in the suppression of metastatic colonization in ovarian cancer
  • MAP2K4 and MAP2K7 are required for optimal activation of JNKs in a synergistic fashion but MAP2K4 can also affect the second stress kinase pathway MAPK14
  • antagonizes cardiomyocyte hypertrophy
  • new role for MAP2K4 in regulating GJA1 expression and preventing hypertrophy-associated arrhythmogenesis
  • regulates GJA1 transcription most likely by virtue of two AP-1 binding sites in the GJA1 proximal promoter region
  • critical cardiac protector preventing hypertrophy-associated ventricular arrhythmias through restriction of GJA1 remodeling
  • MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis
  • plays a crucial role in the stress-activated signal cascade and is enzymatically regulated by ligand or substrate binding, and/or post-translational modification
  • is essential during embryogenesis and involved in a variety of physiological and pathological processes
  • has not always a definite function, but rather triggers a cellular reaction in concert with other modulators
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • components of the two MAPK cascades, MAP3K5-MAP2K4-MAPK10 and RAF1-MAPK1-MAP2K1 interacting with arrestins
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TRIB1
  • ARR3 binds MAPK10, MAP2K4, and MAP3K5
  • MAP2K4 and MAP2K7 compete for ARR3 binding
  • TGFB1I1 serves as a novel scaffold protein that specifically activates MAP2K4/MAPK8 pathway, thereby leading to the induction and activation of MMP in smooth muscle cells and subsequent abdominal aortic aneurysm (AAA) formation
  • YTHDF2 depletion increased the expression and stability of MAP2K4 and MAP4K4 mRNAs
  • cell & other
    REGULATION
    activated by phosphorylation on ser/thr by map kinase kinase kinases
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in pancreatic, lung, prostate, breast, and colorectal carcinomas with metastases
    constitutional     --low  
    age-downregulated in the frontal cortex
    tumoral     --low  
    in ovarian carcinoma
    tumoral     --over  
    in rhabdomyosarcoma (Pazzaglia 2009)
    Susceptibility to sporadic pancreatic cancer
    Variant & Polymorphism SNP
  • rs12939944 located in the MAP2K4 intron was associated with decreased risk of sporadic pancreatic cancer
  • Candidate gene
    Marker
  • MAPK7 and MAP2K4 could be good markers in assessing response to treatment and development of osteosarcoma
  • Therapy target
    SystemTypeDisorderPubmed
    cardiovascularrythm 
    because antagonizes pathological hypertrophy, may lead to the development of better therapies for treating hypertrophy-associated ventricular arrhythmias
    ANIMAL & CELL MODELS
    Sek1 Knockout mice