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

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: mouse all
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Genomic context

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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The deubiquitinase OTUD1 deubiquitinates TIPE2 and plays a protective role in sepsis-induced lung injury by targeting TAK1-mediated MAPK and NF-kappaB signaling.
Title: The deubiquitinase OTUD1 deubiquitinates TIPE2 and plays a protective role in sepsis-induced lung injury by targeting TAK1-mediated MAPK and NF-κB signaling.
TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers.
Title: TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers.
The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review.
Title: The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review.
USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.
Title: USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.
Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators.
Title: Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators.
Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis.
Title: Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis.
SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1-Dependent Manner.
Title: SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1-Dependent Manner.
Emerging role of TAK1 in the regulation of skeletal muscle mass.
Title: Emerging role of TAK1 in the regulation of skeletal muscle mass.
MAP3K7 is an innate immune regulatory gene with increased expression in human and murine kidney intercalated cells following uropathogenic Escherichia coli exposure.
Title: MAP3K7 is an innate immune regulatory gene with increased expression in human and murine kidney intercalated cells following uropathogenic Escherichia coli exposure.
Enhanced expression of mRNA for transforming growth factor beta activated kinase 1 in CD34+ cells of the bone marrow in rheumatoid arthritis.
Title: Enhanced expression of mRNA for transforming growth factor β activated kinase 1 in CD34+ cells of the bone marrow in rheumatoid arthritis.

Submit: New GeneRIF Correction See all GeneRIFs (186)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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 EBI GWAS CatalogPubMed
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies ALLC polymorphisms correlated with FEV&#x02081; change by corticosteroid. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-132368 (e-PCR)
- UniSTS:184321

D6S1420 (e-PCR)
- UniSTS:38663

STS-N93759 (e-PCR)
- UniSTS:65830

WI-19992 (e-PCR)
- UniSTS:75830

SHGC-24062 (e-PCR)
- UniSTS:45135

RH36246 (e-PCR)
- UniSTS:78955

G33039 (e-PCR)
- UniSTS:117616

RH16422 (e-PCR)
- UniSTS:80035

SHGC-34216 (e-PCR)
- UniSTS:61151

A010A09 (e-PCR)
- UniSTS:51198

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 JUN kinase kinase kinase activity	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 more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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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

EC 2.7.11.25

NP_663304.1

EC 2.7.11.25

NP_663305.1

EC 2.7.11.25

NP_663306.1

EC 2.7.11.25

XP_006715616.1

EC 2.7.11.25

XP_054212245.1

EC 2.7.11.25

NCBI Reference Sequences (RefSeq)

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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

NG_011966.2 RefSeqGene

Range

5117..78610

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003188.4 → NP_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:42 → 292

STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1
NM_145331.3 → NP_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:42 → 292

STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1
NM_145332.3 → NP_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:42 → 292

STKc_TAK1; Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1
NM_145333.3 → NP_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:42 → 292

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

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

90513579..90587072 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A8V8TQF2

Conserved Domains (1) summary

cl21453
Location:1 → 162

PKc_like; Protein Kinases, catalytic domain