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Updated: Jun 7, 2026

Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
Regulation of NAT1 activity in modern humans by a novel phosphorylation site
Luise Fast1, Mikel Lana Alberro1, Eva Rakava1
1Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Abstract:
N-acetyltransferase 1 (NAT1) is an enzyme that acetylates certain drugs and carcinogens and is involved in folate metabolism. Some NAT1 variants are associated with susceptibility to cancer and birth defects. We show that while nearly all present-day humans carry a valine residue at position 149 and a serine residue at position 214, some carry the ancestral amino acids isoleucine and alanine at these positions because of gene flow from Neanderthals. Neither substitution affects enzymatic activity. However, replacing the serine residue, a known phosphorylation site, with a phosphomimetic aspartate reduces NAT1 activity by ~60%. Phosphorylation at this site may allow NAT1 to be down-regulated during pregnancy to reduce birth defect risk, while maintaining high activity in adults for xenobiotic clearance. This regulatory site is a molecular feature that differs between modern humans and Neanderthals.
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