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    MAP3K5 mitogen-activated protein kinase kinase kinase 5 [ Homo sapiens (human) ]

    Gene ID: 4217, updated on 5-Jul-2015
    Official Symbol
    MAP3K5provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 5provided by HGNC
    Primary source
    HGNC:HGNC:6857
    See related
    Ensembl:ENSG00000197442; HPRD:03904; MIM:602448; Vega:OTTHUMG00000015647
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ASK1; MEKK5; MAPKKK5
    Summary
    Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]
    Orthologs
    See MAP3K5 in Epigenomics, MapViewer
    Location:
    6q22.33
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 6 NC_000006.12 (136557046..136793051, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (136878184..137113656, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene microtubule-associated protein 7 Neighboring gene NADH dehydrogenase (ubiquinone) Fe-S protein 5, 15kDa (NADH-coenzyme Q reductase) pseudogene 1 Neighboring gene uncharacterized LOC105378015 Neighboring gene uncharacterized LOC101928461 Neighboring gene RNA, 5S ribosomal pseudogene 219 Neighboring gene uncharacterized LOC105378016 Neighboring gene uncharacterized LOC101928429 Neighboring gene peroxisomal biogenesis factor 7 Neighboring gene ribosomal protein L7a pseudogene 37 Neighboring gene solute carrier family 35, member D3

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Binding of HIV-1 gp120 to DC-SIGN leads to excessive ASK-1 activation and promotes ASK-1-dependent apoptosis in human dendritic cells PubMed
    Nef nef HIV-1 Nef inhibits ASK1-induced phosphorylation of p54/p46 JNK in cells. Nef mutant (152DEVGEANN/AAAAAAAA159) abolishes its inhibitory activity PubMed
    nef Mutations within the motif (152DEVGEANN159) of HIV-1 Nef impair its ability to interact with ASK1 and restore ASK1 anti-apoptosis function PubMed
    nef Amino acids 152-159 in HIV-1 Nef and the N-terminal region (residues 1-318) and the C-terminal region (residues 905-1051) of ASK1 are involved in the binding between Nef and ASK1 PubMed
    nef Inhibition of ASK1 by HIV-1 Nef leads to the inhibition of both Fas- and TNFalpha-mediated apoptosis, as well as the inhibition of the activation of the downstream c-Jun amino-terminal kinase PubMed
    nef HIV-1 Nef inhibits ASK1 catalytic activity by impairing stimulus-coupled release of its normal negative regulator, thioredoxin PubMed
    nef Nef inhibits ASK1/p38MAPK-dependent Mycobacterium tuberculosis-induced TNF-alpha production by inhibiting binding of ATF2 to the TNF-alpha promoter PubMed
    nef HIV-1 Nef binds to ASK1 as demonstrated by GST-pull down and coimmunoprecipitation experiments PubMed

    Go to the HIV-1, Human Interaction Database

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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MAP kinase kinase kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein kinase binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    JNK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of JUN kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    activation of MAPKK activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to hydrogen peroxide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to reactive nitrogen species IEA
    Inferred from Electronic Annotation
    more info
     
    innate immune response IEA
    Inferred from Electronic Annotation
    more info
     
    intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    intrinsic apoptotic signaling pathway in response to oxidative stress IDA
    Inferred from Direct Assay
    more info
    PubMed 
    p38MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of JNK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of JUN kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of myoblast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of neuron death IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of neuron death ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    programmed necrotic cell death IEA
    Inferred from Electronic Annotation
    more info
     
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to ischemia IEA
    Inferred from Electronic Annotation
    more info
     
    viral process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    IRE1-TRAF2-ASK1 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    protein kinase complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    mitogen-activated protein kinase kinase kinase 5
    Names
    ASK-1
    MAP/ERK kinase kinase 5
    MAPK/ERK kinase kinase 5
    MEK kinase 5
    MEKK 5
    apoptosis signal regulating kinase 1
    apoptosis signal-regulating kinase 1
    NP_005914.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011965.1 RefSeqGene

      Range
      5001..240470
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_005923.3NP_005914.1  mitogen-activated protein kinase kinase kinase 5

      See identical proteins and their annotated locations for NP_005914.1

      Status: REVIEWED

      Source sequence(s)
      U67156
      Consensus CDS
      CCDS5179.1
      UniProtKB/Swiss-Prot
      Q99683
      Related
      ENSP00000351908, OTTHUMP00000017275, ENST00000359015, OTTHUMT00000042383
      Conserved Domains (3) summary
      smart00220
      Location:685938
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam13281
      Location:165545
      DUF4071; Domain of unknown function (DUF4071)
      cd06624
      Location:671938
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p2 Primary Assembly

      Range
      136557046..136793051
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011535838.1XP_011534140.1  

      Conserved Domains (3) summary
      smart00220
      Location:685938
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam13281
      Location:165545
      DUF4071; Domain of unknown function (DUF4071)
      cd06624
      Location:671938
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
    2. XM_011535837.1XP_011534139.1  

      Conserved Domains (3) summary
      smart00220
      Location:649902
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam13281
      Location:165545
      DUF4071; Domain of unknown function (DUF4071)
      cd06624
      Location:635902
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
    3. XM_011535839.1XP_011534141.1  

      Conserved Domains (3) summary
      smart00220
      Location:685938
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam13281
      Location:165545
      DUF4071; Domain of unknown function (DUF4071)
      cd06624
      Location:671938
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase

    Alternate CHM1_1.1

    Genomic

    1. NC_018917.2 Alternate CHM1_1.1

      Range
      137140796..137376381
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)