Version 5.4
Homo sapiens Gene: MAP3K7
Summary
InnateDB Gene IDBG-94374.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol MAP3K7
Gene Name mitogen-activated protein kinase kinase kinase 7
Synonyms MEKK7; TAK1; TGF1a
Species Homo sapiens
Ensembl Gene ENSG00000135341
Encoded Proteins
IDBP-94376
mitogen-activated protein kinase kinase kinase 7
IDBP-94378
mitogen-activated protein kinase kinase kinase 7
IDBP-94380
mitogen-activated protein kinase kinase kinase 7
IDBP-94382
mitogen-activated protein kinase kinase kinase 7
IDBP-94384
mitogen-activated protein kinase kinase kinase 7
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 10187861
MAP3K7 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase family that, together with its activator TAK1-binding protein 1 (TAB1), activates the IKK signallosome and thus regulates NF-kappaB activation.
PMID 17965022
MAP3K7 is an essential intermediate of NOD2 signalling where MAP3K7 deletion completely abolishes muramyl dipeptide (MDP)-NOD2 signalling, activation of NF-kappaB and MAPKs, and the subsequent induction of cytokines/chemokines in keratinocytes.
PMID 10675530
MAP3K7 mediates the activation signal from TLRs to nuclear factor-kappaB in lipopolysaccharide-stimulated macrophages.
PMID 16260493
MAP3K7 acts as an upstream activating kinase for IKBKB (IKK-beta) and MAPK8 (JNK), but not CHUK (IKK-alpha), revealing a specific role of MAP3K7 in inflammatory signalling pathways.
PMID 8533096
MAP3K7 (TAK1) functions as a mediator in the signalling pathway of TGF-beta superfamily members.
PMID 9480845
MAP3K7 induces NF-kappaB activation through a MAP3K14 (NIK)-independent signalling pathway.
PMID 10094049
MAP3K7 links TRAF6 to the MAP3K14 (NIK)-IKK cascade in the IL-1 signalling pathway where activated MAP3K7 phosphorylates NIK, which stimulates IKK-alpha activity.
PMID 20065289
MAP3K7 is a target for glucocorticoids that integrates their anti-inflammatory action in innate immunity signalling pathways.
PMID 20200282
MAP3K7 plays a central role in controlling nuclear and cytoplasmic signalling cascades in primary neutrophils where it constitutively associates with the IKBKB (I-kappa-B kinase) complex in the nucleus and cytoplasm, impacting downstream signalling processes.
PMID 21220427
MAP3K7 activation is impaired during endotoxin tolerization; a process which impairs the production of LPS-induced pro-inflammatory cytokines without inhibition expression of anti-inflammatory or anti-microbial mediators.
PMID 22069318
MAP3K7 polyubiquitination is essential for the activation of NF-kB signalling downstream of TNF receptor, IL1 receptor and TLR4.
PMID 22843747
MAP3K7 is necessary for the neutrophil priming effect of leukotriene B (4) to enhance TLR stimulation. (Demonstrated in mice)
PMID 25028512
MAP3K7 (TAK1) Ser412 phosphorylation is regulated by PRKACA and PRKX, and is essential for proper signalling, as well as proinflammatory cytokine induction by TLR/IL-1R activation.
PMID 25371197
ECSIT binds to MAP3K7 and TRAF6 to form a complex that plays a pivotal role in activating TLR4-mediated NF-kB signalling.
PMID 26082489
Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
InnateDB Annotation from Orthologs
Summary
PMID 21220427
[Mus musculus] Map3k7 activation is impaired during endotoxin tolerization; a process which impairs the production of LPS-induced pro-inflammatory cytokines without inhibition expression of anti-inflammatory or anti-microbial mediators.
PMID 22069318
[Mus musculus] Map3k7 polyubiquitination is essential for the activation of NF-kB signalling downstream of TNF receptor, IL1 receptor and Tlr4.
PMID 22843747
[Mus musculus] Map3k7 is necessary for the neutrophil priming effect of leukotriene B (4) to enhance TLR stimulation.
Entrez Gene
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 6:90513573-90587045
Strand Reverse strand
Band q15
Transcripts
ENST00000369329 ENSP00000358335
ENST00000369332 ENSP00000358338
ENST00000369327 ENSP00000358333
ENST00000369325 ENSP00000358331
ENST00000369320 ENSP00000358326
ENST00000479630
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 231 experimentally validated interaction(s) in this database.
They are also associated with 50 interaction(s) predicted by orthology.
Experimentally validated
Total 231 [view]
Protein-Protein 224 [view]
Protein-DNA 4 [view]
Protein-RNA 0
DNA-DNA 3 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 50 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004708 MAP kinase kinase activity
GO:0004709 MAP kinase kinase kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0097110 scaffold protein binding
Biological Process
GO:0000165 MAPK cascade
GO:0000186 activation of MAPKK activity
GO:0000187 activation of MAPK activity
GO:0001525 angiogenesis
GO:0001841 neural tube formation
GO:0002224 toll-like receptor signaling pathway
GO:0002726 positive regulation of T cell cytokine production
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006351 transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0007252 I-kappaB phosphorylation
GO:0007254 JNK cascade
GO:0032743 positive regulation of interleukin-2 production
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043507 positive regulation of JUN kinase activity
GO:0043966 histone H3 acetylation
GO:0045087 innate immune response (InnateDB)
GO:0046330 positive regulation of JNK cascade
GO:0050852 T cell receptor signaling pathway
GO:0050870 positive regulation of T cell activation
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051403 stress-activated MAPK cascade
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:1902443 negative regulation of ripoptosome assembly involved in necroptotic process
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2001234 negative regulation of apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005671 Ada2/Gcn5/Ada3 transcription activator complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0008385 IkappaB kinase complex
GO:0010008 endosome membrane
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
ENSMUSG00000028284
View Gene Order
ENSBTAG00000002625
Not yet available
Pathways
NETPATH
NetPath_7
TGF_beta_Receptor pathway
NetPath_8
Wnt pathway
NetPath_9
TNFalpha pathway
NetPath_12
BCR pathway
NetPath_13
IL1 pathway
NetPath_18
IL6 pathway
NetPath_21
RANKL pathway
NetPath_26
TWEAK pathway
REACTOME
REACT_21368
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
REACT_21399
activated TAK1 mediates p38 MAPK activation pathway
REACT_25351
TRAF6 mediated induction of TAK1 complex pathway
REACT_21281
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_25380
IRAK2 mediated activation of TAK1 complex pathway
REACT_6788
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_8005
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_8006
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_25018
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation pathway
REACT_25024
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_25222
MyD88 dependent cascade initiated on endosome pathway
REACT_9047
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_27215
MyD88 cascade initiated on plasma membrane pathway
REACT_9027
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_9061
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_75776
NOD1/2 Signaling Pathway pathway
REACT_12555
Downstream TCR signaling pathway
REACT_22442
Interleukin-1 signaling pathway
REACT_118656
Activation of NF-kappaB in B cells pathway
REACT_163994
FCERI mediated NF-kB activation pathway
REACT_9020
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_172761
Ca2+ pathway pathway
REACT_172694
beta-catenin independent WNT signaling pathway
REACT_12526
TCR signaling pathway
REACT_11045
Signaling by Wnt pathway
REACT_75790
Cytokine Signaling in Immune system pathway
REACT_6802
Innate Immune System pathway
REACT_7980
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_163936
Fc epsilon receptor (FCERI) signaling pathway
REACT_111102
Signal Transduction pathway
REACT_21308
MAP kinase activation in TLR cascade pathway
REACT_75913
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
REACT_75774
Adaptive Immune System pathway
REACT_6900
Immune System pathway
REACT_22232
Signaling by Interleukins pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_118773
Signaling by the B Cell Receptor (BCR) pathway
REACT_118638
Downstream signaling events of B Cell Receptor (BCR) pathway
KEGG
hsa04310
Wnt signaling pathway pathway
hsa04010
MAPK signaling pathway pathway
hsa04520
Adherens junction pathway
hsa04660
T cell receptor signaling pathway pathway
hsa04620
Toll-like receptor signaling pathway pathway
hsa04622
RIG-I-like receptor signaling pathway pathway
hsa04621
NOD-like receptor signaling pathway pathway
hsa05140
Leishmaniasis pathway
hsa04380
Osteoclast differentiation pathway
hsa05145
Toxoplasmosis pathway
INOH
INOH website
CD4 T cell receptor signaling pathway
INOH website
IL-7 signaling pathway
INOH website
IL-1 signaling pathway pathway
INOH website
Toll-like receptor signaling pathway pathway
INOH website
JAK STAT pathway and regulation pathway
INOH website
B cell receptor signaling pathway
INOH website
EPO signaling pathway pathway
INOH website
Wnt signaling pathway pathway
INOH website
VEGF signaling pathway pathway
INOH website
TGF-beta signaling pathway
INOH website
BMP2 signaling pathway
PID NCI
bmppathway
BMP receptor signaling
ps1pathway
Presenilin action in Notch and Wnt signaling
il1pathway
IL1-mediated signaling events
tnfpathway
TNF receptor signaling pathway
bcr_5pathway
BCR signaling pathway
cmyb_pathway
C-MYB transcription factor network
ephrinbrevpathway
Ephrin B reverse signaling
tcrjnkpathway
JNK signaling in the CD4+ TCR pathway
tgfbrpathway
TGF-beta receptor signaling
wnt_noncanonical_pathway
Noncanonical Wnt signaling pathway
p38_mkk3_6pathway
p38 MAPK signaling pathway
Cross-References
SwissProt
TrEMBL Q9UG54
UniProt Splice Variant
Entrez Gene 6885
UniGene Hs.594838 Hs.644143
RefSeq NM_003188 NM_145331 NM_145332 NM_145333 XM_006715553
HUGO HGNC:6859
OMIM 602614
CCDS CCDS5027 CCDS5028 CCDS5029 CCDS5030
HPRD 04011
IMGT
EMBL AL050393 AL121837 AL121964
GenPept CAB43687
RNA Seq Atlas 6885

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca