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

    Gene ID: 4217, updated on 17-Jun-2024

    Summary

    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 MIM:602448; AllianceGenome:HGNC:6857
    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]
    Expression
    Broad expression in adrenal (RPKM 43.3), ovary (RPKM 21.3) and 23 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See MAP3K5 in Genome Data Viewer
    Location:
    6q23.3
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (136557046..136793091, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (137745240..137981287, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (136878184..137113615, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene microtubule associated protein 7 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:136870396-136870934 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17572 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17573 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:136871473-136872010 Neighboring gene RN7SK pseudogene 299 Neighboring gene MPRA-validated peak6148 silencer Neighboring gene MAP7 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25115 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:136933733-136934303 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:136934304-136934873 Neighboring gene MAP3K5 antisense RNA 1 Neighboring gene RNA, 5S ribosomal pseudogene 219 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90326 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25116 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90334 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25117 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25118 Neighboring gene uncharacterized LOC124901410 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25120 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25121 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25119 Neighboring gene Sharpr-MPRA regulatory region 8718 Neighboring gene Sharpr-MPRA regulatory region 14394 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:137112365-137112880 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25122 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17575 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25123 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25125 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25124 Neighboring gene MAP3K5 antisense RNA 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:137143334-137144066 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:137144067-137144799 Neighboring gene MPRA-validated peak6150 silencer Neighboring gene MPRA-validated peak6151 silencer Neighboring gene small nucleolar RNA SNORA27 Neighboring gene peroxisomal biogenesis factor 7 Neighboring gene ribosomal protein L7a pseudogene 37

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    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
    Vif vif ASK1 restricts the replication of HIV-1 by inhibiting Vif activity and promoting APOBEC3G incorporation into virions in CD4+ T-cells PubMed
    vif ASK1 inhibits the interaction of HIV-1 Vif with ELOB/C in a dose-dependent manner, whereas no significant change is observed in the binding of Vif with CUL5 or CBFbeta PubMed
    vif ASK1 markedly inhibits HIV-1 Vif-induced ubiquitination of APOBEC3G by a reduction in the Vif-ELOC interaction PubMed
    vif The BC box (amino-acid residues 144-149) of HIV-1 Vif binds the C-terminal domain (amino-acid residues 955-1374) of ASK1 PubMed
    vif ASK1 directly binds HIV-1 Vif and inhibits the anti-APOBEC3G activity by Vif PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables JUN kinase kinase kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables MAP kinase kinase kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables MAP kinase kinase kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein domain specific binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein kinase binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    involved_in JNK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in JNK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cellular response to amino acid starvation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to hydrogen peroxide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to reactive nitrogen species IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to stress IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cellular response to tumor necrosis factor IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular senescence TAS
    Traceable Author Statement
    more info
     
    involved_in endothelial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in intrinsic apoptotic signaling pathway in response to oxidative stress IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in intrinsic apoptotic signaling pathway in response to oxidative stress IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neuron intrinsic apoptotic signaling pathway in response to oxidative stress IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in p38MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of JNK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of JUN kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cardiac muscle cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of myoblast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of p38MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of vascular associated smooth muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in programmed necrotic cell death IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in response to ischemia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in stress-activated MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of IRE1-TRAF2-ASK1 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    part_of protein kinase complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of protein-containing complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 

    General protein information

    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
    NP_005914.1
    XP_011534141.2
    XP_016866361.1
    XP_016866362.1
    XP_016866364.1
    XP_016866366.1
    XP_047274740.1
    XP_047274741.1
    XP_047274742.1
    XP_047274743.1
    XP_054211428.1
    XP_054211429.1
    XP_054211430.1
    XP_054211431.1
    XP_054211432.1
    XP_054211433.1
    XP_054211434.1
    XP_054211435.1
    XP_054211436.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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
      5042..240473
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_005923.4NP_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)
      AL024508, AL121933
      Consensus CDS
      CCDS5179.1
      UniProtKB/Swiss-Prot
      A6NIA0, B4DGB2, Q5THN3, Q99461, Q99683
      UniProtKB/TrEMBL
      Q59GL6
      Related
      ENSP00000351908.4, ENST00000359015.5
      Conserved Domains (3) summary
      smart00220
      Location:685938
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06624
      Location:671938
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
      pfam13281
      Location:165544
      DUF4071; Domain of unknown function (DUF4071)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      136557046..136793091 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010875.2XP_016866364.1  mitogen-activated protein kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      Q59GL6
    2. XM_047418784.1XP_047274740.1  mitogen-activated protein kinase kinase kinase 5 isoform X3

      UniProtKB/TrEMBL
      Q59GL6
    3. XM_017010873.2XP_016866362.1  mitogen-activated protein kinase kinase kinase 5 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TMH5, Q59GL6
      Related
      ENSP00000514039.1, ENST00000698928.1
    4. XM_017010872.2XP_016866361.1  mitogen-activated protein kinase kinase kinase 5 isoform X1

      UniProtKB/TrEMBL
      Q59GL6
    5. XM_047418785.1XP_047274741.1  mitogen-activated protein kinase kinase kinase 5 isoform X7

      UniProtKB/TrEMBL
      B4DF67
    6. XM_017010877.2XP_016866366.1  mitogen-activated protein kinase kinase kinase 5 isoform X6

      UniProtKB/TrEMBL
      B4DF67
    7. XM_011535839.4XP_011534141.2  mitogen-activated protein kinase kinase kinase 5 isoform X5

      UniProtKB/TrEMBL
      Q59GL6
    8. XM_047418786.1XP_047274742.1  mitogen-activated protein kinase kinase kinase 5 isoform X8

    9. XM_047418787.1XP_047274743.1  mitogen-activated protein kinase kinase kinase 5 isoform X9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      137745240..137981287 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355455.1XP_054211430.1  mitogen-activated protein kinase kinase kinase 5 isoform X3

      UniProtKB/TrEMBL
      Q59GL6
    2. XM_054355456.1XP_054211431.1  mitogen-activated protein kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      Q59GL6
    3. XM_054355454.1XP_054211429.1  mitogen-activated protein kinase kinase kinase 5 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TMH5, Q59GL6
    4. XM_054355453.1XP_054211428.1  mitogen-activated protein kinase kinase kinase 5 isoform X1

      UniProtKB/TrEMBL
      Q59GL6
    5. XM_054355459.1XP_054211434.1  mitogen-activated protein kinase kinase kinase 5 isoform X7

      UniProtKB/TrEMBL
      B4DF67
    6. XM_054355458.1XP_054211433.1  mitogen-activated protein kinase kinase kinase 5 isoform X6

      UniProtKB/TrEMBL
      B4DF67
    7. XM_054355457.1XP_054211432.1  mitogen-activated protein kinase kinase kinase 5 isoform X5

      UniProtKB/TrEMBL
      Q59GL6
    8. XM_054355460.1XP_054211435.1  mitogen-activated protein kinase kinase kinase 5 isoform X8

    9. XM_054355461.1XP_054211436.1  mitogen-activated protein kinase kinase kinase 5 isoform X9