Alpha-tubulin N-acetyltransferase 1 (ATAT1)

Alpha-tubulin N-acetyltransferase 1 (ATAT1) is the major enzyme responsible for acetylating lysine 40 (K40) of α-tubulin, a posttranslational modification crucial for microtubule stability and function across many species, including humans[2][5][6]. ATAT1 is a single-domain acetyltransferase belonging to the GNAT family and localizes to clathrin-coated pits for this activity[4][5]. Its function is essential for numerous diverse biological processes, such as ciliogenesis, neuronal migration, autophagy, and cell migration, where it regulates the acetylation of microtubules impacting stability and cellular signaling[1][6]. Deficiency in ATAT1 leads to defective hippocampal development, sperm motility (male infertility), and impaired cell migration, with important implications in neurodevelopmental disease and cancer metastasis[1][6]. While currently no drugs directly modulate ATAT1, it remains a critical target for therapeutic development, and its activity is monitored via biomarkers such as acetylated α-tubulin (K40)[6]. Safety concerns for drugs targeting ATAT1 center on the risk of broadly disturbing cell division, neural function, and tissue homeostasis due to its fundamental role in microtubule biology.

Other names

Alpha-tubulin N-acetyltransferase 1ATAT1C6orf134MEC17Nbla00487Alpha-TATAlpha-TAT1TATFLJ13158Acetyltransferase mec-17 homolog

Enzyme modulation (potential for inhibitors/modulators targeting tubulin acetylation), Regulation of microtubule stability and function