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

Gene ID: 6885, updated on 5-Jul-2020

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
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

Genomic context

See MAP3K7 in Genome Data Viewer
Location:
6q15
Exon count:
17
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (90513579..90587072, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (91223292..91297020, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene BTB domain and CNC homolog 2 Neighboring gene uncharacterized LOC105377890 Neighboring gene uncharacterized LOC105377891 Neighboring gene microRNA 4464 Neighboring gene uncharacterized LOC107986623 Neighboring gene uncharacterized LOC105377893 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

NHGRI GWAS Catalog

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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
MAP kinase kinase kinase activity EXP
Inferred from Experiment
more info
PubMed 
MAP kinase kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
MAP kinase kinase kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
magnesium ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein serine/threonine kinase activity EXP
Inferred from Experiment
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 
receptor tyrosine kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
scaffold protein binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
I-kappaB kinase/NF-kappaB signaling TAS
Traceable Author Statement
more info
 
I-kappaB phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
JNK cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
JNK cascade IDA
Inferred from Direct Assay
more info
PubMed 
JNK cascade TAS
Traceable Author Statement
more info
 
MyD88-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
T cell receptor signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
Wnt signaling pathway, calcium modulating pathway TAS
Traceable Author Statement
more info
 
activation of MAPK activity IDA
Inferred from Direct Assay
more info
PubMed 
activation of MAPK activity TAS
Traceable Author Statement
more info
 
activation of MAPKK activity IDA
Inferred from Direct Assay
more info
PubMed 
activation of NF-kappaB-inducing kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
anoikis ISS
Inferred from Sequence or Structural Similarity
more info
 
histone H3 acetylation IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-1-mediated signaling pathway TAS
Traceable Author Statement
more info
 
nucleotide-binding oligomerization domain containing signaling pathway TAS
Traceable Author Statement
more info
 
positive regulation of I-kappaB kinase/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of JUN kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of JUN kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity TAS
Traceable Author Statement
more info
 
positive regulation of T cell cytokine production IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of interleukin-2 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of macroautophagy ISS
Inferred from Sequence or Structural Similarity
more info
 
protein deubiquitination TAS
Traceable Author Statement
more info
 
stimulatory C-type lectin receptor signaling pathway TAS
Traceable Author Statement
more info
 
stress-activated MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Ada2/Gcn5/Ada3 transcription activator complex IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with IkappaB kinase complex IPI
Inferred from Physical Interaction
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
endosome membrane TAS
Traceable Author Statement
more info
 
nucleus HDA PubMed 
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_016866715.1

NCBI Reference Sequences (RefSeq)

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/Swiss-Prot
    O43318
    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
    O43318
    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/Swiss-Prot
    O43318
    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/Swiss-Prot
    O43318
    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: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

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

mRNA and Protein(s)

  1. XM_006715553.3XP_006715616.1  mitogen-activated protein kinase kinase kinase 7 isoform X1

    Conserved Domains (1) summary
    cl21453
    Location:1162
    PKc_like; Protein Kinases, catalytic domain
  2. XM_017011226.2XP_016866715.1  mitogen-activated protein kinase kinase kinase 7 isoform X2

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