TGF-beta-activated kinase 1 and MAP3K7-binding protein 2

Definition:

Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains. The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1. Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (By similarity). Involved in heart development.

References:

[1]. C Wang, et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001 Jul 19;412(6844):346-51. [Content Brief]

[2]. Li Zhang, et al. Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation. Nature. 2011 Dec 11;481(7380):204-8. [Content Brief]

[3]. Bernard Thienpont, et al. Haploinsufficiency of TAB2 causes congenital heart defects in humans. Am J Hum Genet. 2010 Jun 11;86(6):839-49. [Content Brief]

[4]. Atsuhiro Kanayama, et al. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell. 2004 Aug 27;15(4):535-48. [Content Brief]

[5]. G Takaesu, et al. TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Mol Cell. 2000 Apr;5(4):649-58. [Content Brief]

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