TAB2

Phenotypes

Mouse phenotype:

Homozygous deletion of Tab2 is embryonic lethal at E12.5.

Subcellular localization

cilia, basal body

References: doi:10.1371/journal.pbio.3003902

Functional category

• Non-motile cilium / primary cilium
• Cardiac & muscle development
• Protein processing & maturation

Function

Adaptor that activates TAK1 (MAP3K7) and, on the evidence of Doganli et al. 2026, does so at the primary cilium. Immunofluorescence in RPE-1 cells shows prominent TAB2 localization at the ciliary base and additionally at the ciliary tip. During P19CL6 cardiomyocyte differentiation TAB2 is progressively recruited to the primary cilium, rising significantly and peaking around day 10, in contrast to total ciliary TAK1 and PKA-Calpha which stay comparatively stable; 3D voxel imaging places TAB2 predominantly at the ciliary base region. TAB2 recruitment is the step that, with PKA-Calpha, drives TAK1 phosphorylation and activation at this site in response to TGFB1 and BMP2. Functionally, CRISPR-Cas9 Tab2 knockout P19CL6 cells show severely delayed cardiomyogenesis with reduced GATA4 and absent striated Troponin-I and alpha-actinin, and zebrafish tab2 mutants phenocopy tak1 mutants with pericardial edema, enlarged atria, reduced ventricular trabeculation, atrioventricular valve defects, hypoplastic outflow tract and craniofacial and pectoral fin anomalies. DOI 10.1371/journal.pbio.3003902