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FLASH GENE
Symbol MAP4K4 contributors: mct - updated : 15-10-2014
HGNC name mitogen-activated protein kinase kinase kinase kinase 4
HGNC id 6866
Location 2q11.2      Physical location : 102.314.487 - 102.511.151
Synonym name
  • HPK/GCK-like kinase
  • hepatocyte progenitor kinase-like/germinal center kinase-like kinase
  • Synonym symbol(s) KIAA0687, HGK, FLH21957, FLJ10410, FLJ20373, FLJ90111, HEL-S-31, MEKKK4, NIK
    EC.number 2.7.1.37/2.7.11.1
    DNA
    TYPE EST
    STRUCTURE 196.98 kb     31 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned   linked   status provisional
    Map cen - D2S113 - RPL31 - ATP5BL1 - MAP4K4 - D2S373 - D2S176 - qter
    Authors Gene Map (98)
    Physical map
    LOC389010 2 LOC389010 NPAS2 2p11.2-q12 neuronal PAS domain protein 2 RPL31 2q12.1 ribosomal protein L31 TBC1D8 2q12.1 TBC1 domain family, member 8 (with GRAM domain) C40 2q12.1 hypothetical protein C40 LOC389011 2 LOC389011 LOC391410 2 similar to peptidyl-Pro cis trans isomerase RNF149 2q12.1 ring finger protein 149 CREG2 2q11.2 ring finger protein 149 LOC389012 2 similar to hypothetical protein MGC33442 LOC389013 2 LOC389013 LOC389014 2 LOC389014 LOC391411 2 similar to ribosomal protein S6 LOC391412 2 similar to Lysosomal Pro-X carboxypeptidase precursor (Prolylcarboxypeptidase) (PRCP) (Proline carboxypeptidase) (Angiotensinase C) (Lysosomal carboxypeptidase C) MAP4K4 2q11.2 mitogen-activated protein kinase kinase kinase kinase 4 FLJ20373 2q12.1 hypothetical protein FLJ20373 IL1R2 2q12 interleukin 1 receptor, type II IL1R1 2q12 interleukin 1 receptor, type I IL1RL2 2q12 interleukin 1 receptor-like 2 IL1RL1 2q12 interleukin 1 receptor-like 1 IL18R1 2q12 interleukin 18 receptor 1 IL18RAP 2p24.3-p24.1 interleukin 18 receptor accessory protein LOC389015 2 similar to Sodium/hydrogen exchanger 4 (Na(+)/H(+) exchanger 4) (NHE-4) SLC9A2 2q11.2 solute carrier family 9 (sodium/hydrogen exchanger), isoform 2
    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
  • 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