Abhydrolase domain-containing protein 14B (ABHD14B)

Abhydrolase domain-containing protein 14B (ABHD14B) is an atypical lysine deacetylase (KDAC), classified in the metabolic serine hydrolase enzyme family. It catalyzes the transfer of acetyl groups from acetylated lysine residues of proteins to coenzyme A (CoA), thereby generating acetyl-CoA and regenerating protein lysine's free amine. ABHD14B contains a canonical α/β-hydrolase domain fold with a conserved catalytic triad (Ser-His-Asp) and acts through a ping-pong mechanism typical for serine hydrolases[1][2][3][4]. Structurally, it is an outlier among KDACs, differing from both sirtuins and HDACs in using CoA as a co-substrate. ABHD14B is expressed predominantly in metabolically active tissues such as liver, kidney, and pancreas[1]. Functional studies reveal its role in modulating cellular and systemic glucose metabolism, especially under fasting conditions; knockdown or disruption impairs glycolysis and TCA cycle flux and leads to reduced acetyl-CoA levels[1]. It also interacts with the HAT domain of transcription factor TAFII250, suggesting relevance in transcriptional regulation[1][2][4]. While there is growing interest in ABHD14B as a metabolic regulator and potential therapeutic target in diseases involving metabolic dysregulation or energy homeostasis (e.g., cancer, obesity), there are currently no known drugs or clinical inhibitors, and endogenous substrates remain to be fully classified.

Other names

Putative protein-lysine deacylase ABHD14BCIBCCG1-interacting factor BCCG1/TAFII250-interacting factor Balpha/beta hydrolase domain-containing protein 14Bcell cycle gene 1-interacting factor BHEL-S-299epididymis secretory protein Li 299epididymis secretory sperm binding proteinMGC15429