U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination
    • Showing Current items.

    MAP3K7 mitogen-activated protein kinase kinase kinase 7 [ Homo sapiens (human) ]

    Gene ID: 6885, updated on 8-Apr-2024

    Summary

    Official Symbol
    MAP3K7provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 7provided by HGNC
    Primary source
    HGNC:HGNC:6859
    See related
    Ensembl:ENSG00000135341 MIM:602614; AllianceGenome:HGNC:6859
    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
    CSCF; FMD2; TAK1; MEKK7; TGF1a
    Summary
    The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 10.0), endometrium (RPKM 9.4) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Location:
    6q15
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (90513579..90587072, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (91725183..91798324, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (91223298..91296791, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377891 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 6:91036267 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 6:91037287 Neighboring gene MPRA-validated peak5961 silencer Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:91078586-91079785 Neighboring gene microRNA 4464 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:91095435-91096029 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:91117202-91117738 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24835 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr6:91123479-91124420 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:91122537-91123478 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24836 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17399 Neighboring gene uncharacterized LOC124901362 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:91204071-91204730 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:91204758-91205314 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:91205315-91205871 Neighboring gene Sharpr-MPRA regulatory region 8521 Neighboring gene MPRA-validated peak5962 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr6:91296727-91296923 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17400 Neighboring gene uncharacterized LOC124901363 Neighboring gene NANOG hESC enhancer GRCh37_chr6:91307010-91307575 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:91319600-91320100 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:91320101-91320601 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17401 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:91321559-91322507 Neighboring gene uncharacterized LOC107986623 Neighboring gene uncharacterized LOC105377893 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:91379294-91380249 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:91380250-91381204 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:91383116-91384071 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:91384072-91385026 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:91385983-91386936 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:91388246-91389050 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:91489789-91490333 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:91617235-91618434 Neighboring gene NANOG hESC enhancer GRCh37_chr6:91624822-91625331 Neighboring gene NANOG hESC enhancer GRCh37_chr6:91867325-91867853 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:92007857-92008449 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:92008450-92009041 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:92009042-92009634 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:92009635-92010225 Neighboring gene uncharacterized LOC107986624

    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?

    Phenotypes

    Associated conditions

    Description Tests
    Cardiospondylocarpofacial syndrome
    MedGen: C2931461 OMIM: 157800 GeneReviews: Not available
    Compare labs
    Frontometaphyseal dysplasia 2
    MedGen: C4310697 OMIM: 617137 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies two new risk loci for Graves' disease.
    EBI GWAS Catalog
    Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
    EBI GWAS Catalog
    Genome-wide association study identifies ALLC polymorphisms correlated with FEV₁ change by corticosteroid.
    EBI GWAS Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    EBI GWAS Catalog

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of mitogen-activated protein kinase kinase kinase 7 (MAP3K7) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 Env co-localizes with TAK1 in cells PubMed
    Envelope transmembrane glycoprotein gp41 env The HIV-1 gp41 cytoplasmic domain-induced NFkappaB activation requires TAK1, RelA, and NEMO proteins PubMed
    env The 12 amino-acid cytoplasmic domain (residues 762-773) of HIV-1 gp41 directly interacts with TAK1 and gp41 colocalizes with TAK1 in cells PubMed
    Nef nef IL-32-treated M2-macrophages result in the weak activation of p38, IKK alpha/beta, and MAP3K7 (TAK1) by HIV-1 Nef PubMed
    nef HIV-1 Nef-induced strong activation of MAP kinases (p38/MAPK14, JNK/MAPK8, and ERK1/2) and NF-kappaB pathway (IKK alpha/beta) in M2-macrophages is mediated by MAP3K7 (TAK1) PubMed
    nef HIV-1 Nef induces strong phosphorylation of MAP3K7 (TAK1) in M2-macrophages but not in M1-macrophages PubMed
    Vpr vpr HIV-1 (NL43) Vpr S79A mutant, which no longer binds TAK1, demonstrates impaired ability to trigger TNF-alpha secretion from MT4C5 cells suggesting TAK1/Vpr interaction enhances TNF secretion from HIV-1 infected cells PubMed
    vpr Activation of TAK1 by HIV-1 Vpr leads to increased levels of phosphorylated IKK-beta and MKK7 in cells PubMed
    vpr The ability of HIV-1 Vpr to activate NF-kappaB or activator protein 1-dependent luciferase expression requires TAK1, TRAF6, or TAB3 in cells PubMed
    vpr HIV-1 Vpr-induced phosphorylation of TAK1 requires TRAF6 and Vpr increases the polyubiquitination of TAK1 in cells PubMed
    vpr HIV-1 Vpr induces phosphorylation of TAK1 in both HeLa and HEK293T cells through its association with TAK1 in cells PubMed
    capsid gag MAP3K7 (TAK1) is required for Trim12B-PP1A(CypA) fusion protein-mediated restriction of VSV-G-pseudotyped HIV-1 transduction in HEK293 cells PubMed
    gag MAP3K7 (TAK1) is required for Trim12A-PP1A(CypA) fusion protein-mediated restriction of VSV-G-pseudotyped HIV-1 transduction in HEK293 cells PubMed
    gag The TAK1 kinase complex (TAK1/TAB2/TAB3) contributes to capsid-specific restriction mediated by TRIM5alpha. TRIM5alpha activates TAK1 autophosphorylation 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 IEA
    Inferred from Electronic Annotation
    more info
     
    enables DNA-binding transcription factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables MAP kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables MAP kinase kinase kinase activity EXP
    Inferred from Experiment
    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 MAP kinase kinase kinase kinase activity TAS
    Traceable Author Statement
    more info
     
    enables histone kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables linear polyubiquitin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables magnesium ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein 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 EXP
    Inferred from Experiment
    more info
    PubMed 
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
     
    enables protein serine/threonine kinase binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables receptor tyrosine kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables scaffold protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables transcription coactivator binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables type II transforming growth factor beta receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables ubiquitin protein ligase binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in Fc-epsilon receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in I-kappaB phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in JNK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in JNK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in JNK cascade TAS
    Traceable Author Statement
    more info
     
    involved_in MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in MyD88-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in T cell receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in TRIF-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in activation of NF-kappaB-inducing kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in anoikis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in canonical NF-kappaB signal transduction TAS
    Traceable Author Statement
    more info
     
    involved_in cellular response to angiotensin IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to tumor necrosis factor IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cytoplasmic pattern recognition receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in defense response to bacterium IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in interleukin-1-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in interleukin-1-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in interleukin-17A-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in interleukin-33-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in p38MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in p38MAPK cascade TAS
    Traceable Author Statement
    more info
     
    involved_in positive regulation of JUN kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of T cell cytokine production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of cell size IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of interleukin-2 production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of macroautophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of non-canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of vascular associated smooth muscle cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of vascular associated smooth muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in stimulatory C-type lectin receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in stress-activated MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in toll-like receptor 3 signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in toll-like receptor 4 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in transforming growth factor beta receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of ATAC complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytoplasm IC
    Inferred by Curator
    more info
    PubMed 
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in endosome membrane TAS
    Traceable Author Statement
    more info
     
    located_in nucleus HDA PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
     

    General protein information

    Preferred Names
    mitogen-activated protein kinase kinase kinase 7
    Names
    TGF-beta activated kinase 1
    transforming growth factor-beta-activated kinase 1
    NP_003179.1
    NP_663304.1
    NP_663305.1
    NP_663306.1
    XP_006715616.1
    XP_054212245.1

    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_011966.2 RefSeqGene

      Range
      5117..78610
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003188.4NP_003179.1  mitogen-activated protein kinase kinase kinase 7 isoform A

      See identical proteins and their annotated locations for NP_003179.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (A) lacks an in-frame coding segment, compared to variant B. The resulting isoform (A) lacks an internal region, as compared to isoform B.
      Source sequence(s)
      AB009356, AI147171, AL121964, BM172351
      Consensus CDS
      CCDS5027.1
      UniProtKB/TrEMBL
      Q5U0D0
      Related
      ENSP00000358338.3, ENST00000369332.7
      Conserved Domains (1) summary
      cd14058
      Location:42292
      STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1
    2. NM_145331.3NP_663304.1  mitogen-activated protein kinase kinase kinase 7 isoform B

      See identical proteins and their annotated locations for NP_663304.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (B) encodes the longest isoform (B).
      Source sequence(s)
      AB009357, AI147171, AL121964, BM172351
      Consensus CDS
      CCDS5028.1
      UniProtKB/Swiss-Prot
      B2RE27, E1P523, O43317, O43318, O43319, Q5TDN2, Q5TDN3, Q5TDT7, Q9NTR3, Q9NZ70
      UniProtKB/TrEMBL
      Q5U0C9
      Related
      ENSP00000358335.3, ENST00000369329.8
      Conserved Domains (1) summary
      cd14058
      Location:42292
      STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1
    3. NM_145332.3NP_663305.1  mitogen-activated protein kinase kinase kinase 7 isoform C

      See identical proteins and their annotated locations for NP_663305.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (C) lacks a segment, which leads to a frameshift, compared to variant B. The resulting isoform (C) contains a distinct and shorter C-terminus, as compared to isoform B.
      Source sequence(s)
      AB009358, AI147171, AL121964, BM172351
      Consensus CDS
      CCDS5029.1
      UniProtKB/TrEMBL
      Q5U0C9
      Related
      ENSP00000358331.3, ENST00000369325.7
      Conserved Domains (1) summary
      cd14058
      Location:42292
      STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1
    4. NM_145333.3NP_663306.1  mitogen-activated protein kinase kinase kinase 7 isoform D

      See identical proteins and their annotated locations for NP_663306.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (D) lacks two segments, one of which leads to a frameshift, compared to variant C. The resulting isoform (C) lacks an internal region, and contains a distinct and shorter C-terminus, as compared to isoform B.
      Source sequence(s)
      AF218074, AI147171, AL121964, BM172351
      Consensus CDS
      CCDS5030.1
      UniProtKB/TrEMBL
      B4DRH8
      Related
      ENSP00000358333.3, ENST00000369327.7
      Conserved Domains (1) summary
      cd14058
      Location:42292
      STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1

    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
      90513579..90587072 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006715553.4XP_006715616.1  mitogen-activated protein kinase kinase kinase 7 isoform X1

      UniProtKB/TrEMBL
      A0A8V8TQF2
      Conserved Domains (1) summary
      cl21453
      Location:1162
      PKc_like; Protein Kinases, catalytic domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      91725183..91798324 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356270.1XP_054212245.1  mitogen-activated protein kinase kinase kinase 7 isoform X1