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

Gene ID: 6885, updated on 10-Oct-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
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Genomic context

See MAP3K7 in Genome Data Viewer
Location:
6q15
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (90513579..90587072, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (91725183..91798324, complement)
RS_2024_09 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 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 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 cGAS/STING signaling pathway IDA
Inferred from Direct Assay
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
 
is_active_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
PubMed 
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_2024_08

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