TaB2

TAB2, or TAK1-binding protein 2, is a protein-coding gene in humans. The TAB2 protein functions as an adaptor that links TAK1 (MAP3K7) to receptor-proximal signaling complexes activated by pro-inflammatory stimuli such as interleukin-1, tumor necrosis factor, and Toll-like receptors, enabling downstream activation of inflammatory pathways.

Structurally, TAB2 contains a coiled-coil region that promotes protein–protein interactions and an NZF-type zinc finger domain at the C terminus that binds polyubiquitin chains. This ubiquitin-binding capability helps recruit TAB2 to ubiquitinated signaling complexes and facilitates TAK1 activation in response to receptor stimulation.

Mechanistically, TAB2 participates in the activation of TAK1, which then stimulates the IκB kinase complex to drive NF-κB signaling and also activates p38 and JNK MAP kinases. TAB2 interacts with TAK1 and with other signaling proteins such as TRAF6 and RIP1, contributing to the assembly of signalosomes for IL-1, TNF, and Toll-like receptor pathways.

Clinical significance: Variations in TAB2 and alterations in its expression have been investigated in inflammatory conditions, including arthritis and sepsis, as modifiers of NF-κB– and MAPK-mediated responses. While changes in TAB2 can affect signaling strength, direct causal links to specific diseases remain to be established. In animal models, TAB2 is important for proper inflammatory signaling and normal development.

See also TAB1, TAB3, TAK1, NF-κB signaling.