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FLASH GENE
Symbol MAP2K7 contributors: mct - updated : 12-03-2019
HGNC name mitogen-activated protein kinase kinase 7
HGNC id 6847
DNA
TYPE functioning gene
STRUCTURE 10.70 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map pter - EEF2 - FUT3 - D19S216 - GTF2F1 - INSR - EMR1 - D19S812 - FCER2 - MAP2K7 - RPS28 - D19S413 - cen
Authors Gene Map
RNA
TRANSCRIPTS type messenger
text two isoforms produced by alternative splicing
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 splicing 3386 47 419 - 2006 9372971
- splicing 3900 - 461 - 2006 9372971
- - 1308 - 435 in various normal tissues, tumors, and in synoviocytes from rheumatoid and osteoarthritis patients 2006 9372971
  • can be phosphorylated and activated by MEKK1
  • Filamin A binds to an N-terminal region (residues 31-60) present in the MKK7gamma
  • importance of MKK7gamma1 in its ability to reverse basic cellular programmes by simply using JNKs as effectors
    • 12 - 3525 - 435 - 2006 9372971
    11 - 3498 - 426 - 2006 9372971
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a protein kinase domain
  • a docking site, a stretch of about 20 amino acids immediately on the C-terminal side of the MAPKK catalytic domain (Takekawa 2005)
    • HOMOLOGY
    interspecies ortholog to Drosophila Dhep
    ortholog to C.elegans
    homolog to murine Map2k7
    homolog to F35c8.3
    Homologene
    FAMILY
  • MAP (mitogen-activated-protein) kinase family
  • Dual specificity protein kinase family
    • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • activating JNK
  • involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses
  • works as a cytoplasmic anchoring protein for JNK1 in various types of cells, including human peripheral blood mononuclear cell (PBMC) T-cells
  • acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of TP53, which is required for cell cycle arrest and suppression of epithelial cancers
  • is a vital molecular sensor to set a cellular anti-cancer barrier
  • 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
  • functions as a tumor suppressor for epithelial cancers of the lung, mammary gland and skin downstream of various oncogenes
  • MAP2K7 undergoes likely neddylation in human breast cancer cells, which limits its basal kinase activity
  • is an indispensable kinase of the JUN N-terminal kinase signal cascade and is rigorously regulated via phosphorylation
    • CELLULAR PROCESS protein
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • MAP2K7-MAPK8 signaling plays an important regulatory role in neural development, and MAP2K7-MAPK8 signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with DUSP19 to negatively regulate JNK pathway
  • interacting with GADD45B (could induce cardiomyocytes hypertrophic response and GADD45B could inhibit the enzymatic activity of MAP2K7 by contacting critical residues in the catalytic domain)
  • FLNA, FLNB and FLNC interact with MAP2K4 and MAP2K7, but not with JNK
  • ARR3 directly binds MAP2K7
  • MAP2K4 and MAP2K7 compete for ARR3 binding
  • ARR3 promotes MAPK10 phosphorylation by MAP2K7
  • stimulation of nTregs through TNFRSF18 initiates a signaling cascade that involves MAP2K7, MAPK8 phosphorylation, JUN activation, and the activation of NFKB1
  • activates the JUN N-terminal kinase (MAPK8) pathway and is the only MKK containing three motifs within its regulatory domain
  • KLF4 represses the gene encoding the kinase MAP2K7
  • GADD45 proteins bind the JNK kinase mitogen-activated protein kinase kinase 7 (MAP2K7) and inhibit its activity, even under normal physiological conditions
  • MAP2K7, which selectively phosphorylates MAPK8, is a SENP3 substrate and SENP3-mediated deSUMOylation of MAP2K7 may favor its binding to MAPK8
    • cell & other
    REGULATION
    activated by phosphorylation
    FLNA (Filamin A enhances MAP2K7 activation and is important for synergistic stress-induced JNK activation)
    inhibited by CYLD
    Other MAP kinase in the JUNK pathway
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    of the MAP2K7-JUN N-terminal kinase (JNK) signalling cascade may underlie some of the neurochemical changes and core symptoms in schizophrenia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS