TAB2 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, OMIM

TAB2 (TGF-Beta Activated Kinase 1 Binding Protein 2) encodes a scaffold protein that links upstream signals to the MAP3K7 (TAK1) kinase complex. It is essential for the activation of NF-κB and JNK pathways in response to pro-inflammatory cytokines (e.g., IL-1, TNF-α) and Toll-like receptor (TLR) ligands. TAB2 contains a C-terminal zinc finger domain that binds polyubiquitin chains, facilitating TAK1 activation. The gene is critical for embryonic development, particularly cardiac morphogenesis, and its dysregulation is associated with congenital heart defects, inflammatory disorders, and various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• IL-1 signaling pathway (Reactome: R-HSA-446652)

• TNF signaling pathway (Reactome: R-HSA-168164)

• Toll-like receptor signaling pathway (Reactome: R-HSA-168898)

• TAK1-dependent NF-κB activation (Reactome: R-HSA-445989)

• JNK (c-Jun N-terminal kinase) signaling (Reactome: R-HSA-450341)

TAB2 is a 693-amino acid scaffold protein (UniProt Q9NYJ8) that contains an N-terminal kinase-binding domain, a coiled-coil region, and a C-terminal zinc finger (NZF) domain that binds K63-linked polyubiquitin chains. It forms a complex with TAB1 and TAK1 (MAP3K7), and upon stimulation by cytokines or pathogens, TAB2 recruits TAK1 to ubiquitin chains, leading to TAK1 autophosphorylation and subsequent activation of IKK (NF-κB) and MKK4/7 (JNK) pathways. The protein is predominantly cytoplasmic but can shuttle to the nucleus. Post-translational modifications include phosphorylation and ubiquitination, which regulate its stability and activity.