Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly. acetyl-CoA + L-lysyl-[alpha-tubulin] = CoA + H(+) + N(6)-acetyl-L-lysyl-[alpha-tubulin] Component of the BBSome complex (By similarity). Interacts with AP2 alpha-adaptins, including AP2A2, but not with AP1 gamma-adaptin (AP1G1/AP1G2); this interaction is required for efficient alpha-tubulin acetylation, hence clathrin-coated pits are sites of microtubule acetylation. In primary root dorsal ganglion neurons, localizes with acetylated tubulin in axons. Recruited to the mitotic spindle during cell division. Widely expressed with highest levels in neuronal tissues. In the brain, expressed in the cortex, cerebellum and hippocampus, including the pyramidal layers in CA1 and CA3, as well as the granular cell layers in the lateral blade (suprapyramidal portion) and the medial blade (infrapyramidal portion) of the dentate gyrus. In testis, mainly expressed in the internal cell layers of seminiferous tubules, where spermatocytes and spermatids are located. Widely expressed in embryos during development with particularly high expression in the spinal cord at 13.5 dpc. Autoacetylation strongly increases tubulin acetylation. Mutant mice are viable and show no overt phenotype. Drastic loss of tubulin acetylation in all tissues anlyzed, including in early embryos. In dorsal hippocampus, but not in ventral hippocampus, the dentate gyrus is slightly deformed, showing a prominent bulge in the lateral blade of the granular cell layers. In addition, the lateral ventricle appears to be dilated (PubMed:23720746). Homozygous mutant males exhibit decreased fertility (PubMed:23748901). Mature spermatozoa from cauda epididymis often show the presence of a cytoplasmic droplet attached to the annulus of the tail, indicative of impaired maturation. The flagella length is also significantly decreased in spermatozoa, especially in those cells with a cytoplasmic droplet. Spermatozoa display significantly lower motility than control sperm. However, sperm flagella display the characteristic 9 + 2 organization of axoneme microtubules (PubMed:23748901). Belongs to the acetyltransferase ATAT1 family.