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Symbol MAP3K5 contributors: mct - updated : 13-05-2011
HGNC name mitogen-activated protein kinase kinase kinase 5
HGNC id 6857
Location 6q23.3      Physical location : 136.878.187 - 137.113.656
Synonym name
  • apoptosis signal-regulating kinase 1
  • MAPK/ERK kinase kinase 5
  • extracellular signal-regulated kinase
  • MEK kinase 5
  • Synonym symbol(s) MAPKK1, MEK1, MEKK5, MAPKKK5, ASK1
    TYPE functioning gene
    STRUCTURE 235.47 kb     30 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure a non-consensus E2F-binding site located 12 bp upstream of the transcription start site, the -95/+11 region critical for E2F-mediated up-regulation
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC391971 6 similar to keratin 8; cytokeratin 8; keratin, type II cytoskeletal 8 LOC391972 6 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein FAM8A6P 6q23 family with sequence similarity 8, member A6 pseudogene LOC154094 6q23.2 similar to Protein CGI-27 (C21orf19-like protein) ALDH8A1 6q24.1-q25.1 aldehyde dehydrogenase 8 family, member A1 HBS1L 6q23-q24 HBS1-like (S. cerevisiae) MYB 6q23.3-q24 v-myb myeloblastosis viral oncogene homolog (avian) AHI1 6q23.2 Abelson helper integration site LOC391973 6 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) PDE7B 6q23-q24 phosphodiesterase 7B DUFD1 6q23.2 DUF729 domain containing 1 BTF 6q23 DUF729 domain containing 1 MAP7 6q23.3 microtubule-associated protein 7 MAP3K5 6q22.33 mitogen-activated protein kinase kinase kinase 5 PEX7 6q21-q22.2 peroxisomal biogenesis factor 7 SLC35D3 6q23.2 solute carrier family 35, member D3 IL20RA 6q23.3 interleukin 20 receptor, alpha IL22RA2 6q24-q25.1 interleukin 22 receptor, alpha 2 IFNGR1 6q23-q24 interferon gamma receptor 1 OLIG3 6q23.3 oligodendrocyte transcription factor 3 LOC391974 6 similar to RIKEN cDNA 5730434I03 gene LOC134897 6q23.3 similar to protein tyrosine phosphatase TNFAIP3 6q23-q25 tumor necrosis factor, alpha-induced protein 3 PERP 6q24 PERP, TP53 apoptosis effector PBOV1 6q23-q24 prostate and breast cancer overexpressed 1 KIAA1244 6q23.3 KIAA1244 HEBP2 6q24 heme binding protein 2 KIAA1357 6q23.3 KIAA1357 protein LOC389430 6 LOC389430 C6orf80 6q23.1-q24.1 chromosome 6 open reading frame 80
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    30 - 5215 154 1374 - 2009 19004820
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineadrenal gland   highly
     pancreas   highly
     thyroid   highly
    Lymphoid/Immunelymph node   highly
    Reproductivemale systemprostate  highly
    Respiratoryrespiratory tracttrachea  highly
    Urinarybladder   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  predominantly
    cell lineage
    cell lines
    fluid/secretion highly in blood
    at STAGE
  • an N-terminal auto-inhibitory domain
  • a kinase catalytic domain with eleven kinases subdomains (hybrid between those of serine/threonine and tyrosine protein kinases)
  • a thioredoxin-binding domain
  • two distinct motifs, C-terminal and kinase domain, additively contribute to its repressive activity on 26 S proteasome (
  • conjugated PhosphoP
    mono polymer homomer , dimer , polymer
    interspecies homolog to murine Map3k5 (94.6 pc)
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP kinase kinase kinase subfamily
  • CATEGORY enzyme , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • acting as a serine/threonine protein kinase and as an activator of p38 MAPK signaling cascades
  • involved in the caspase-independent pathway
  • phosphorylating and activating MAP2K4 and MAP2K6
  • activating c-jun terminal kinase (JNK)/stress activated protein kinase (SAPK), in response to TNF-alpha and FasL
  • phosphorylates cardiac troponin T to regulate cardiac contractile function
  • playing an essential role in cell death induced by ER stress
  • plays an essential role in stress and immune response and linked to the development of several diseases
  • with MAP3K6, are critically involved in tumorigenesis by differentially regulating apoptosis and inflammation
  • role in the regulation of 26 S proteasome
  • potentially acting as a novel binding partner of SMN and controls the steady-state level of SMN through complex formation with SMN in neurite outgrowth
  • CELLULAR PROCESS cell life, cell death/apoptosis
    text embryonic development
    signaling signal transduction
    component of a protein kinase signal transduction cascade
    a component
  • homo-oligomerization
  • inactive homodimer
  • components of the two MAPK cascades, MAP3K5-MAP2K4-MAPK10 and c-Raf-1-MEK1-ERK2
    small molecule metal binding, nucleotide,
  • Mg2+
  • ATP
  • protein
  • TRAF family
  • PPP5C
  • ARBB2
  • DAXX
  • DUSP19
  • interacting with AKT2 and DAB2IP
  • binding to PKR
  • forming a complex with IGF1R
  • direct E2F1 target gene
  • interacts with PRDX1 via its thioredoxin-binding domain (interaction highly inducible by H2O2)(Kim 2008)
  • interacting with PGAM5 (associates with the MAP kinase kinase kinase MAP3K5 and acts as a specific protein Ser/Thr phosphatase that activates MAP3K5 by dephosphorylation of inhibitory sites)
  • association between MAP3K5 and STRAP is mediated through the C-terminal domain of MAP3K5 and the fourth and sixth WD40 repeats of STRAP
  • stabilizes SMN protein by inhibiting SMN poly-ubiquitination, and the kinase activity of MAP3K5 is less important than its ability to bind to SMN
  • ZNF622 physically interact with MAP3K5
  • ARR3 binds MAPK10, MAP2K4, and MAP3K5
  • MAP3K5 a representative stress kinase, interacts with both GAPDH and SIAH1 and is likely able to phosphorylate Siah1 at specific amino acid residues
  • cell & other
    activated by TRAF2, TRAF5, TRAF6 overexpression
    PPP3R1 through direct dephosphorylation
    phosphorylation at Thr-842
    various stress stimuli, including cytokines (TNF), serum deprivation, genotoxic chemicals, reactive oxygen species and agents that trigger ER stress
    induced by DAXX
    inhibited by IGF1R via its phosphorylation on a tyrosine residue, resulting in a decreased JNK1 stimulation
    HIV-1 Nef
    phosphorylation at Ser-966 and Ser-1033
    phosphorylation of serine 967 (promoting MAP3K5 binding to 14-3-3, an event associated with suppression of MAP3K5 function)
    Other regulated by reactive oxygen species through dephosphorylation
    phosphorylated by PIM1
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    activated in response to diverse stresses and apoptotic stimuli that participate in the pathogenesis and exacerbation of various diseases (
    tumoral somatic mutation      
    in metastatic melanoma
    Variant & Polymorphism
    Candidate gene
    Therapy target
    could be a new target for mechanistic approaches aimed at stabilizing proteasomal activity under various stresses
    could be a new target for mechanistic approaches aimed at stabilizing proteasomal activity under various
    Activation of apoptosis signal regulating kinase 1 (MAP3K5) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid