MAP3K7
GeneName
MAP3K7
Summary
MAP3K7, also known as TAK1 or TAK-1, is a 67kDa serine/threonine kinase that plays a pivotal role in various signalling pathways, particularly those related to stress responses and inflammation. It is localised in multiple cellular compartments, including the cytoplasm, nucleus, and various membrane structures such as the plasma membrane and endoplasmic reticulum. MAP3K7 functions as an essential mediator in the canonical NF-kappaB signalling pathway, as well as in MAPK cascades, influencing processes such as immune response, cellular stress responses, and apoptosis. It interacts with a variety of proteins, including receptor tyrosine kinases and transcription factors, thereby regulating gene expression and cellular activities in response to extracellular signals.
Importance
MAP3K7 is relevant to: - The regulation of inflammatory responses and immune system activation, particularly through its role in NF-kappaB signalling. - The modulation of cellular responses to stress and damage, making it a potential target in cancer and degenerative diseases. - The influence on T cell function and cytokine production, which is crucial for adaptive immunity. - Its involvement in various signalling pathways related to cardiovascular health and smooth muscle cell behaviour, indicating its role in vascular biology.
Top Products
For researchers investigating MAP3K7, we highly recommend the top-selling recombinant antibody, Anti-TAK1 antibody [EPR5984] (ab109526). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). With 75 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable detection of MAP3K7.
Abcam Product Citation Summary
The data indicates that MAP3K7 is being investigated in the context of TNF-α signalling and osteoclast differentiation. The use of human and mouse models highlights its relevance in both human cellular responses and murine bone biology.
Abcam Product Citation Table
Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545).
Involvement in disease
Frontometaphyseal dysplasia 2
FMD2
A form of frontometaphyseal dysplasia, a progressive sclerosing skeletal dysplasia affecting the long bones and skull. Characteristic features include supraorbital hyperostosis, cranial hyperostosis, undermodeling of the small bones, flared metaphyses, and digital anomalies. Extra-skeletal manifestations include hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. FMD2 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Cardiospondylocarpofacial syndrome
CSCF
A syndrome characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. CSCF transmission pattern is consistent with autosomal dominant inheritance.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Association with TAB1/MAP3K7IP1 promotes autophosphorylation at Ser-192 and subsequent activation. Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7. Dephosphorylation at Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and PPP6C leads to inactivation.
'Lys-48'-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation. Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH (By similarity). Requires 'Lys-63'-linked polyubiquitination for autophosphorylation and subsequent activation. 'Lys-63'-linked ubiquitination does not lead to proteasomal degradation. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Deubiquitinated by Y.enterocolitica YopP.
(Microbial infection) Cleaved and inactivated by the proteases 3C of coxsackievirus A16 and human enterovirus D68, allowing the virus to disrupt TRAF6-triggered NF-kappa-B induction.
(Microbial infection) Acetylation of Thr-184 and Thr-187 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
Sequence Similarities
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Tissue Specificity
Isoform 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form.
Cellular localization
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.
Alternative names
TAK1, MAP3K7, Mitogen-activated protein kinase kinase kinase 7, Transforming growth factor-beta-activated kinase 1, TGF-beta-activated kinase 1
Database links
swissprot:O43318 omim:602614 entrezGene:6885
Other research areas
- Oncology