{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Keskitalo S"],"funding":["Institut National de la Santé et de la Recherche Médicale (National Institute of Health and Medical Research)","Agence Nationale de la Recherche (French National Research Agency)"],"pagination":["586"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12808100"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["Short linear motifs (SLiMs) in disordered protein regions direct numerous protein-protein interactions, yet most remain uncharacterized. The Asn-Pro-Phe (NPF) motif is a well-known EH-domain ligand implicated in endocytosis, but here we reveal that the non-catalytic subunit of human DNA polymerase ε (POLE2) also serves as a general NPF-motif receptor. Using a quantitative \"native holdup\" assay, we find that POLE2 selectively binds diverse NPF-containing peptides, including canonical EH-domain ligands (e.g., SYNJ1) and previously uncharacterized motifs. Biochemical measurements and mutational analyses show that NPF motifs interact with a shallow pocket near the POLE2 C-terminus, and AlphaFold predictions confirm key roles for Y513, E520, and S522 in motif coordination. Proteome-scale affini"],"journal":["Nature communications"],"pubmed_title":["The non-catalytic DNA polymerase ε subunit is an NPF motif recognition protein."],"pmcid":["PMC12808100"],"funding_grant_id":["ANR-24-ERCS-0002","ATIP-Avenir"],"pubmed_authors":["Zambo B","Gogl G","Varjosalo M","Deutsch N","Keskitalo S","Malaymar Pinar D","Tuhkala A","Davey N","Salokas K","Dosztanyi Z","Turunen T"],"additional_accession":[]},"is_claimable":false,"name":"The non-catalytic DNA polymerase ε subunit is an NPF motif recognition protein.","description":"Short linear motifs (SLiMs) in disordered protein regions direct numerous protein-protein interactions, yet most remain uncharacterized. The Asn-Pro-Phe (NPF) motif is a well-known EH-domain ligand implicated in endocytosis, but here we reveal that the non-catalytic subunit of human DNA polymerase ε (POLE2) also serves as a general NPF-motif receptor. Using a quantitative \"native holdup\" assay, we find that POLE2 selectively binds diverse NPF-containing peptides, including canonical EH-domain ligands (e.g., SYNJ1) and previously uncharacterized motifs. Biochemical measurements and mutational analyses show that NPF motifs interact with a shallow pocket near the POLE2 C-terminus, and AlphaFold predictions confirm key roles for Y513, E520, and S522 in motif coordination. Proteome-scale affini","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T15:39:39.112Z","creation":"2026-06-02T03:09:05.729Z"},"accession":"S-EPMC12808100","cross_references":{"pubmed":["41390769"],"doi":["10.1038/s41467-025-67284-5"]}}