ArticlePloS one2012
Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.Science advances · 2017Trial
- Proteomic alterations associated with residual disease in neoadjuvant chemotherapy treated ovarian cancer tissues.Clinical proteomics · 2022Article
- Proteomic profiling spotlights the molecular targets and the impact of the natural antivirulent umbelliferone on stress response, virulence factors, and the quorum sensing network ofFrontiers in cellular and infection microbiology · 2022Article
- A conserved female-specific larval requirement for MtnB function facilitates sex separation in multiple species of disease vector mosquitoes.Parasites & vectors · 2021Article
- Cardioprotective role of APIP in myocardial infarction through ADORA2B.Cell death & disease · 2019Article
- Revisiting the methionine salvage pathway and its paralogues.Microbial biotechnology · 2019Article
- Launching the C-HPP neXt-CP50 Pilot Project for Functional Characterization of Identified Proteins with No Known Function.Journal of proteome research · 2018Article
- Airway Mucosal Host Defense Is Key to Genomic Regulation of Cystic Fibrosis Lung Disease Severity.American journal of respiratory and critical care medicine · 2018Article
- Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.PloS one · 2017Article
- Php4 Is a Key Player for Iron Economy in Meiotic and Sporulating Cells.G3 (Bethesda, Md.) · 2016Article
- Contribution of Drosophila TRPA1 to Metabolism.PloS one · 2016Article
- C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 complex assembly and supercomplex stabilization.Molecular and cellular biology · 2015Article
- Network analysis in the identification of special mechanisms between small cell lung cancer and non-small cell lung cancer.Thoracic cancer · 2014Article
- Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- A framework for application of metabolic modeling in yeast to predict the effects of nsSNV in human orthologs.Biology direct · 2014Article
- Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Structure of mediator of RhoA-dependent invasion (MRDI) explains its dual function as a metabolic enzyme and a mediator of cell invasion.Biochemistry · 2013Article
- Article
- A Role for Two-Pore Channel Type 2 (TPC2)-Mediated Regulation of Membrane Contact Sites During Zebrafish Notochord Biogenesis?Contact (Thousand Oaks (Ventura County, Calif.))Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The methionine salvage pathway is widely distributed among some eubacteria, yeast, plants and animals and recycles the sulfur-containing metabolite 5-methylthioadenosine (MTA) to methionine. In eukaryotic cells, the methionine salvage pathway takes place in the cytosol and usually involves six enzymatic activities: MTA phosphorylase (MTAP, EC 2.4.2.28), 5'-methylthioribose-1-phosphate isomerase (mtnA, EC 5.3.1.23), 5'-methylthioribulose-1-phosphate dehydratase (mtnB, EC: 4.2.1.109), 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase (mtnC, EC 3.1.3.77), aci-reductone dioxygenase (mtnD, EC 1.13.11.54) and 4-methylthio-2-oxo-butanoate (MTOB) transaminase (EC 2.6.1.-). The aim of this study was to complete the available information on the methionine salvage pathway in human by identifying the enzyme responsible for the dehydratase step. Using a bioinformatics approach, we propose that a protein called APIP could perform this role. The involvement of this protein in the methionine salvage pathway was investigated directly in HeLa cells by transient and stable short hairpin RNA interference. We show that APIP depletion specifically impaired the capacity of cells to grow in media where methionine is replaced by MTA. Using a Shigella mutant auxotroph for methionine, we confirm that the knockdown of APIP specifically affects the recycling of methionine. We also show that mutation of three potential phosphorylation sites does not affect APIP activity whereas mutation of the potential zinc binding site completely abrogates it. Finally, we show that the N-terminal region of APIP that is missing in the short isoform is required for activity. Together, these results confirm the involvement of APIP in the methionine salvage pathway, which plays a key role in many biological functions like cancer, apoptosis, microbial proliferation and inflammation.
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