biostudies-literatureUnknown48(14)Cardon TMinistère de l'Enseignement supérieur, de la Recherche et de l'InnovationInstitut National de la Santé et de la Recherche MédicaleIt has been recently shown that many proteins are lacking from reference databases used in mass spectrometry analysis, due to their translation templated on alternative open reading frames. This questions our current understanding of gene annotation and drastically expands the theoretical proteome complexity. The functions of these alternative proteins (AltProts) still remain largely unknown. We have developed a large-scale and unsupervised approach based on cross-linking mass spectrometry (XL-MS) followed by shotgun proteomics to gather information on the functional role of AltProts by mapping them back into known signalling pathways through the identification of their reference protein (RefProt) interactors. We have identified and profiled AltProts in a cancer cell reprogramming system: Nucleic acids research7864-7882https://www.ebi.ac.uk/biostudies/studies/S-EPMC7641301biostudies-literatureAlternative proteins are functional regulators in cell reprogramming by PKA activation.PMC7641301Franck JDamato MCoyaud ESalzet MVergara DMaffia MFournier ICardon TLaurent EMNfalseAlternative proteins are functional regulators in cell reprogramming by PKA activation.It has been recently shown that many proteins are lacking from reference databases used in mass spectrometry analysis, due to their translation templated on alternative open reading frames. This questions our current understanding of gene annotation and drastically expands the theoretical proteome complexity. The functions of these alternative proteins (AltProts) still remain largely unknown. We have developed a large-scale and unsupervised approach based on cross-linking mass spectrometry (XL-MS) followed by shotgun proteomics to gather information on the functional role of AltProts by mapping them back into known signalling pathways through the identification of their reference protein (RefProt) interactors. We have identified and profiled AltProts in a cancer cell reprogramming system: 2020-01-01T00:00:00Z2020 Aug2026-04-07T18:54:31.467Z2020-11-19T16:59:30ZS-EPMC76413013232422810.1093/nar/gkaa277