Tubulin alpha-1A chain

Tubulin alpha-1A chain (TUBA1A) is the alpha subunit of the tubulin heterodimer, the fundamental building block of microtubules (UniProt: Q71U36). It participates in microtubule polymerization by cycling between GTP-bound and GDP-bound states, with GTP hydrolysis catalyzed by the alpha-tubulin subunit itself. This process is essential for microtubule dynamics and cellular architecture.

TUBA1A is widely expressed and constitutively required for microtubule function across tissues. Beyond its structural role, mutations in TUBA1A are associated with lissencephaly 3 (LIS3; MIM 611603), a severe neurological disorder characterized by cortical malformation, intellectual disability, motor delay, and seizures (UniProt: Q71U36). These associations reflect the critical importance of microtubule integrity in brain development.

In Alzheimer's Disease, TUBA1A is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Analysis across three subcellular fractions yielded a mean log2 fold-change of −0.57, indicating consistent reduction across the fractionated proteome in human AD brain tissue assessed via TMT-labeled quantitative proteomics.