Affinage mechanistic annotation for ABHD14A (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 4 citations

Affinage mechanistic annotation for ABHD14A (human)

Current model (mechanistic narrative)

ABHD14A is a metabolic serine hydrolase of the α/β-hydrolase superfamily, closely related at the sequence level to ABHD14B, from which it is distinguished by defined sequence determinants PMID:37974539. A soluble N-terminally truncated form is an active enzyme that preferentially hydrolyzes short-chain esters, and its p-nitrophenyl-acetate hydrolysis is enhanced by CoA, consistent with a ping-pong type acetyltransferase mechanism analogous to ABHD14B [PMID:bio_10.1101_2025.11.28.691245]. Heterologously expressed full-length protein localizes to the Golgi apparatus, while endogenous protein is undetectable across immortalized cell lines and adult mouse tissues despite transcriptomic predictions [PMID:bio_10.1101_2025.11.28.691245]. At the transcriptional level, ABHD14A (Dorz1) is positively regulated by the zinc-finger transcription factor Zic1 in cerebellar granule neuron precursors PMID:14667578. Beyond these findings, the physiological substrates and in vivo role of ABHD14A have not been characterized in the available corpus.

Affinage mechanism profile (Affinage's own GO/Reactome grounding)

Dated findings (citation-anchored)

Year Confidence Finding PMIDs Journal
2023 Medium ABHD14A is a member of the metabolic serine hydrolase superfamily with high sequence similarity to ABHD14B; bioinformatics coupled with biochemical experiments identified key sequence determinants distinguishing ABHD14A from ABHD14B, enabling better classification of each enzyme. ABHD14A still lacked functional annotation at the time of this study. PMID:37974539 Proteins
2025 Medium ABHD14A is an active serine hydrolase enzyme that preferentially hydrolyzes short-chain esters, as demonstrated by gel-based activity-based protein profiling (ABPP) and p-nitrophenyl-ester hydrolysis assays using a soluble N-terminally truncated variant. ABHD14A exhibits CoA-dependent enhancement of p-nitrophenyl-acetate hydrolysis, indicative of a ping-pong type acetyltransferase mechanism similar to ABHD14B. PMID:bio_10.1101_2025.11.28.691245 bioRxiv
2025 Medium Upon heterologous expression in HEK293T cells, full-length ABHD14A localizes specifically to the Golgi apparatus, suggesting a specialized role in secretory pathway biology. Endogenous ABHD14A protein is undetectable across a panel of immortalized mammalian cell lines and adult mouse tissues, contradicting transcriptomic database predictions. PMID:bio_10.1101_2025.11.28.691245 bioRxiv
2003 Medium Dorz1 (ABHD14A) expression in cerebellar granule neuron precursors is positively regulated by the transcription factor Zic1; Dorz1 was identified as one of the most significantly down-regulated genes in Zic1-deficient cerebellum, and Dorz1 expression was up-regulated in cultured cells overexpressing Zic1. PMID:14667578 Brain research. Molecular brain research
2018 Low Abhd14a mRNA expression is enzymatically upregulated in some tissues of Bphl knockout mice, indicating that ABHD14A expression can be compensatorily induced in the absence of the related serine hydrolase BPHL. PMID:30121252 Biochemical pharmacology

Citations