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FLASH GENE
Symbol MAP2K4 contributors: mct/npt - updated : 19-03-2009
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 122.92 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Physical map
    RPS27AP1 17 ribosomal protein S27a pseudogene 1 MYH13 17p13.1-p12 myosin, heavy polypeptide 13, skeletal muscle MYH8 17p13.1 myosin, heavy polypeptide 8, skeletal muscle, perinatal MYH4 17p13.1 myosin, heavy polypeptide 4, skeletal muscle MYH1 17p13.1 myosin, heavy polypeptide 1, skeletal muscle, adult MYH2 17p13.1 myosin, heavy polypeptide 2, skeletal muscle, adult MYH3 17p13.1 myosin, heavy polypeptide 3, skeletal muscle, embryonic SCO1 17p13-p12 SCO cytochrome oxidase deficient homolog 1 (yeast) MDS006 17p13.1 x 006 protein LOC388335 17 similar to RIKEN cDNA A730055C05 gene LOC388336 17 similar to hypothetical protein D430041B17 LOC284033 17p13.1 hypothetical protein LOC284033 DNAH9 17p12 dynein, axonemal, heavy polypeptide 9 ZNF18 17p13-p12 zinc finger protein 18 (KOX 11) LOC390763 17 similar to 60S ribosomal protein L21 MAP2K4 17p11.2 mitogen-activated protein kinase kinase 4 FLJ34690 17p12 hypothetical protein FLJ34690 LOC390764 17 similar to hypothetical protein MYCD 17p13.3 similar to hypothetical protein KIAA0672 17p11.2 similar to hypothetical protein ELAC2 17p11.2 elaC homolog 2 (E. coli) HS3ST3A1 17p12-p11.2 heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3752 44.16 399 overexpressed in rhabdomyosarcoma Pazzaglia (2009)
    EXPRESSION
    Type widely
    constitutive of
       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
    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
    • 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
    • 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
    Variant & Polymorphism
    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