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FLASH GENE
Symbol MAP4K4 contributors: mct - updated : 15-10-2015
HGNC name mitogen-activated protein kinase kinase kinase kinase 4
HGNC id 6866
RNA
TRANSCRIPTS type messenger
text two proteic isoforms : a shorter of 1165AA without proline-rich domains and a longer of 1175AA with domains, specific of the brain
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
30 - 7334 - 1166 - 2004 14966141
- - 7183 - 1239 - 2004 14966141
31 - 7658 - 1273 - 2004 14966141
31 - 7544 - 1235 - 2004 14966141
- - 7102 - 1212 - 2004 14966141
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestivemouth   highly
Endocrinethyroid   highly
Nervousnervecranial nerve  highly
Reproductivefemale systembreastmammary gland highly
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialsecretoryglandularendocrine 
Epithelialsecretoryglandularexocrine 
Muscularstriatumcardiac  
Muscularstriatumskeletal  
Nervouscentral   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a catalytic kinase domain with 11 kinase subdomains
  • a CNH domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to yeast S.cerevisiae STE20 family murine Nik gene
    Homologene
    FAMILY
  • MAP (mitogen activated protein) kinase family
  • Ste 20 family of serine/threonine protein kinases
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • MAP kinase kinase kinase kinase 4, specifically activating the JNK signaling through the pathway TAK1
  • plays a crucial role in osteopontin (OPN)-induced mitogen-activated protein kinase/I kappa B alpha kinase-dependent nuclear factor kappa B (NF kappa B)-mediated promatrix metalloproteinase-9 activation
  • is a key upstream mediator of TNF action on the beta cell, making it a potential therapeutic target for preservation of beta cell function in type 2 diabetes
  • is a negative regulator of myogenic differentiation and hypertrophy
  • suppressor of skeletal muscle differentiation, acting through a MYF5-dependent mechanism
  • inhibits adipose lipogenesis by suppression of SREBF1 in an AMPK- and MTOR-dependent but JNK-independent mechanism
  • unexpected context-dependent role for MAP4K4, a pluripotent activator of several mitogen-activated protein kinase
  • pathways, in regulating tumor cell survival
  • required for the activation of CD4(+) T cells
  • is essential for CD4(+) T cell proliferation, activation and cytokine production
  • directly phosphorylates TRAF2, leading to its lysosomal degradation and subsequent inhibition of IL6 production
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
    magnesium
    protein
  • interacts with the SH3 domain of the adapter proteins NCK
  • binds, via its CNH regulatory domain, to the N- terminal region of SPG3A
  • N-terminal region of GBP3 binds to the C-terminal regulatory domain of MAP4K4, a member of the group I GCK (germinal center kinase) family
  • is a putative effector of RAP2A mediating the activation of JNK by RAP2A
  • regulates PPARG at a post-transcriptional step
  • MAP4K4 can activate ARF6 via IQSEC1 and enhance focal adhesions dissolution
  • YTHDF2 depletion increased the expression and stability of MAP2K4 and MAP4K4 mRNAs
  • cell & other
    REGULATION
    activated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    induces TRAF2/IL6 upregulation, leading to IL6/leptin-induced Th17 differentiation in adipose tissue and subsequent insulin resistance
    tumoral     --over  
    associated with worse prognosis and is a prognostic marker for stage II pancreatic ductal adenocarcinoma
    constitutional        
    silencing prevents insulin resistance in human skeletal muscle and restores appropriate signaling inputs to enhance glucose uptake
    tumoral     --over  
    is closely associated with lung adenocarcinoma progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker has an independent prognostic value in predicting overall survival for patients with lung adenocarcinoma
    Therapy target
    ANIMAL & CELL MODELS