ArticleNature chemical biology2016
AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Acute exercise-induced lipolysis and increase in levels of fatty acid esters of hydroxy fatty acids in adipose tissue are impaired in obese and aged mice.Experimental physiology · 2026Article
- Whole-Genome Resequencing-Based GWAS Reveals Major-Effect Loci and Candidate Genes for Growth Traits in Topmouth Culter (Animals : an open access journal from MDPI · 2026Article
- Differential Radiomodulatory Effects of Sodium Aminodihydrophthalazinedione (TameronInternational journal of molecular sciences · 2026Article
- ATGL-catalyzed biosynthesis mediates the upregulation of fatty acid hydroxy fatty acids (FAHFA) levels in white adipose tissue with fasting.The Journal of biological chemistry · 2026Article
- The measurement, regulation and biological activity of FAHFAs.Nature chemical biology · 2025Review
- Review
- Reflecting on 20 years of progress.Nature chemical biology · 2025Article
- AIG1 protects against doxorubicin-induced cardiomyocyte ferroptosis and cardiotoxicity by promoting ubiquitination-mediated p53 degradation.Theranostics · 2025Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling.Nature chemistry · 2024Article
- Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels.Nature communications · 2024Article
- Article
- Gender-based heterogeneity of FAHFAs in trained runners.PloS one · 2024Article
- Tissue-specific sex difference in the metabolism of fatty acid esters of hydroxy fatty acids.bioRxiv : the preprint server for biology · 2023Article
- Label-Free Raman Spectromicroscopy Unravels the Relationship between MGMT Methylation and Intracellular Lipid Accumulation in Glioblastoma.Analytical chemistry · 2023Article
- TMEM164 is an acyltransferase that forms ferroptotic C20:4 ether phospholipids.Nature chemical biology · 2023Article
- Activity-based protein profiling - finding general solutions to specific problems.Israel journal of chemistry · 2023Article
- Activity-based annotation: the emergence of systems biochemistry.Trends in biochemical sciences · 2022Review
- Adtrp regulates thermogenic activity of adipose tissue via mediating the secretion of S100b.Cellular and molecular life sciences : CMLS · 2022Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Enzyme classes may contain outlier members that share mechanistic, but not sequence or structural, relatedness with more common representatives. The functional annotation of such exceptional proteins can be challenging. Here, we use activity-based profiling to discover that the poorly characterized multipass transmembrane proteins AIG1 and ADTRP are atypical hydrolytic enzymes that depend on conserved threonine and histidine residues for catalysis. Both AIG1 and ADTRP hydrolyze bioactive fatty acid esters of hydroxy fatty acids (FAHFAs) but not other major classes of lipids. We identify multiple cell-active, covalent inhibitors of AIG1 and show that these agents block FAHFA hydrolysis in mammalian cells. These results indicate that AIG1 and ADTRP are founding members of an evolutionarily conserved class of transmembrane threonine hydrolases involved in bioactive lipid metabolism. More generally, our findings demonstrate how chemical proteomics can excavate potential cases of convergent or parallel protein evolution that defy conventional sequence- and structure-based predictions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.