{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:50:29Z","timestamp":1787014229406,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN2017 2017H4J3AS"],"award-info":[{"award-number":["PRIN2017 2017H4J3AS"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>\n                    Phosphoserine phosphatase (PSP) catalyzes the dephosphorylation of 3\u2010phosphoserine, which is the final step in the\n                    <jats:italic>de novo<\/jats:italic>\n                    biosynthesis of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010serine (\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ser) via the phosphorylated pathway in human astrocytes. Individuals who are homozygous or compound heterozygous for functionally defective PSP variants exhibit reduced cerebrospinal fluid\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ser levels and severe neurological symptoms. In the present study, single nucleotide polymorphisms in PSP were identified in hippocampal samples from Alzheimer's disease (AD) patients. Two single nucleotide polymorphisms, likely forming a haplotype (chr7:56088825 T&gt;A and chr7:56088811 T&gt;C, encoding R27S and D32G PSP variants, respectively), were detected exclusively in AD patients (three females and one male). Biochemical characterization of the recombinant R27S\/D32G PSP enzyme revealed a slight decrease in thermostability, a 38\u2010fold reduction in catalytic efficiency and a two\u2010fold increase in IC\n                    <jats:sub>50<\/jats:sub>\n                    for\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ser, with the D32G substitution being the primary contributor to these effects. Despite its reduced enzyme activity, the R27S\/D32G variant did not impair\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ser biosynthesis either in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    reconstructed pathway or in U251 human glioblastoma cells ectopically expressing the variant under heterozygous conditions. In these cells, PSP colocalized extensively with the other two phosphorylated pathway enzymes, namely phosphoglycerate dehydrogenase and phosphoserine aminotransferase, suggesting that they assemble into a functional complex, known as the serinosome. Notably, the R27S\/D32G PSP variant exhibited increased nuclear localization compared to the wild\u2010type enzyme. This mislocalization raises the intriguing possibility that PSP's moonlighting functions, including its putative role as a protein phosphatase, may be affected, potentially implicating it in pathways beyond\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ser biosynthesis.\n                  <\/jats:p>","DOI":"10.1111\/febs.70169","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T16:50:36Z","timestamp":1752857436000},"page":"4955-4974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A phosphoserine phosphatase variant present in the brain of Alzheimer's disease patients favors nuclear mistargeting"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2338-2561","authenticated-orcid":false,"given":"Silvia","family":"Sacchi","sequence":"first","affiliation":[{"name":"The Protein Factory 2.0, Department of Biotechnology and Life Sciences University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Buoli Comani","sequence":"additional","affiliation":[{"name":"Department of Food and Drug University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Arisi","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI) Rita Levi\u2010Montalcini  Rome Italy"},{"name":"Institute of Translational Pharmacology National Research Council  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4384-9015","authenticated-orcid":false,"given":"Francesco","family":"Marchesani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Rabattoni","sequence":"additional","affiliation":[{"name":"The Protein Factory 2.0, Department of Biotechnology and Life Sciences University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"De Bei","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoraide","family":"Motta","sequence":"additional","affiliation":[{"name":"The Protein Factory 2.0, Department of Biotechnology and Life Sciences University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3254-4099","authenticated-orcid":false,"given":"Alessio","family":"Peracchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-2472","authenticated-orcid":false,"given":"Stefano","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Food and Drug University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-7243","authenticated-orcid":false,"given":"Loredano","family":"Pollegioni","sequence":"additional","affiliation":[{"name":"The Protein Factory 2.0, Department of Biotechnology and Life Sciences University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-0627","authenticated-orcid":false,"given":"Barbara","family":"Campanini","sequence":"additional","affiliation":[{"name":"Department of Food and Drug University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03574-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084231"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4609"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167034"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2012.08633.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0014-2956.2004.04277.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16787"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.81"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010972"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13081219"},{"key":"e_1_2_10_13_1","volume-title":"GeneReviews(R)","author":"Crabben SN","year":"2023"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.7.594"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201083"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12445"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mgene.2021.100897"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-63164-y"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16816"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111271"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0282689"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.2002"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21018"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm259"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-202"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799435"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2020.101896"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24067"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.012"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9921-5"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00361-3"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62245"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jdn.10236"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.1526"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204866200"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12654"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01202-3"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.02.004"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-016-2546-5"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00043"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.02.084"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.02.008"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.12.004"},{"key":"e_1_2_10_45_1","first-page":"604","article-title":"Phosphoserine phosphatase promotes lung cancer progression through the Dephosphorylation of IRS\u20101 and a noncanonical L\u2010serine\u2010independent pathway","volume":"42","author":"Park SM","year":"2019","journal-title":"Mol Cells"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2011.06.001"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00438-9"},{"key":"e_1_2_10_48_1","article-title":"A novel assay for phosphoserine phosphatase exploiting serine acetyltransferase as the coupling enzyme","volume":"11","author":"Marchesani F","year":"2021","journal-title":"Life (Basel)"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471140864.ps2809s79"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(02)00506-7"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(58)90014-6"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801703200"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4792"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203946200"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70169","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.70169","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70169","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:37:20Z","timestamp":1771339040000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.70169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":53,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/febs.70169"],"URL":"https:\/\/doi.org\/10.1111\/febs.70169","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"assertion":[{"value":"2025-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}