TAK1 Recombinant Rabbit Monoclonal Antibody [JM73-19]

Function

Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene. This kinase has also been shown to regulate downstream cytokine expression such as TNF. Due to its regulation of TNF, TAK1 has become a novel target for the treatment of TNF mediated diseases such as auto immune disease ( Rheumatoid Arthritis, lupus, IBD) but also other cytokine mediated disorders such as chronic pain and cancer. With the advent of novel selective TAK1 inhibitors, groups have explored the therapeutic potential of TAK1 targeted therapies. One group has shown that the selective TAK1 inhibitor, Takinib developed at Duke University attenuated rheumatoid arthritis like pathology in the CIA mouse model of human inflammatory arthritis. Furthermore, pharmacological inhibition of TAK1 has shown to reduce inflammatory cytokines in particular TNF.

Background References

1. Ma M et al. TAK1 is an essential kinase for STING trafficking. Mol Cell. 2023 Nov

2. Su W et al. TAK1 deficiency promotes liver injury and tumorigenesis via ferroptosis and macrophage cGAS-STING signalling. JHEP Rep. 2023 Feb

Sequence Similarity

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.

Post-translational Modification

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.

Subcellular Location

Cytoplasm, Cell membrane.

UNIPROT

SwissProt: O43318 Human

SwissProt: Q62073 Mouse

SwissProt: P0C8E4 Rat

Synonyms