Mouse Anti-MAP3K7 Recombinant Antibody (A996) (CBMAB-AP11659LY)

Mitogen-Activated Protein Kinase Kinase Kinase 7

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]

Mitogen-Activated Protein Kinase Kinase Kinase 7; Transforming Growth Factor-Beta-Activated Kinase 1; TGF-Beta Activated Kinase 1; EC 2.7.11.25; TAK1; TGF-Beta-Activated Kinase 1;

A11084

Activation of NF-kappaB-inducing kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
AnoikisISS:BHF-UCL
Cytoplasmic pattern recognition receptor signaling pathwayTAS:Reactome
Fc-epsilon receptor signaling pathwayTAS:Reactome
Histone H3 acetylationManual Assertion Based On ExperimentIDA:BHF-UCL
I-kappaB kinase/NF-kappaB signalingTAS:Reactome
I-kappaB phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Interleukin-1-mediated signaling pathwayTAS:Reactome
JNK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
MyD88-dependent toll-like receptor signaling pathwayTAS:Reactome
Nucleotide-binding oligomerization domain containing signaling pathwayTAS:Reactome
p38MAPK cascadeTAS:Reactome
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of interleukin-2 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JUN kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of macroautophagyISS:BHF-UCL
Positive regulation of NF-kappaB transcription factor activityTAS:Reactome
Positive regulation of T cell cytokine productionManual Assertion Based On ExperimentIMP:UniProtKB
Stimulatory C-type lectin receptor signaling pathwayTAS:Reactome
Stress-activated MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
T cell receptor signaling pathwayTAS:Reactome
Transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm
Cell membrane
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.

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.
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.

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.