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NAD functions as a coenzyme in redox reactions, as a substrate of regulatory proteins, and as a mediator of protein-protein interactions. The main objectives of this study were to identify the NAD-binding and NAD-interacting proteins, and to uncover novel proteins and functions that could be regulated by this metabolite. It was considered if cancer-associated proteins were potential therapeutic targets. Using multiple experimental databases, we defined datasets of proteins that directly interact with NAD \u2013 the <jats:italic>NAD-binding proteins<\/jats:italic> (<jats:italic>NADBPs<\/jats:italic>) dataset \u2013 and of proteins that interact with NADBPs \u2013 the <jats:italic>NAD-protein\u2013protein interactions<\/jats:italic> (<jats:italic>NAD-PPIs<\/jats:italic>) dataset. Pathway enrichment analysis revealed that NADBPs participate in several metabolic pathways, while NAD-PPIs are mostly involved in signalling pathways. These include disease-related pathways, namely, three major neurodegenerative disorders: Alzheimer\u2019s disease, Huntington\u2019s disease, and Parkinson\u2019s disease. Then, the complete human proteome was further analysed to select potential NADBPs. TRPC3 and isoforms of diacylglycerol (DAG) kinases, which are involved in calcium signalling, were identified as new NADBPs. Potential therapeutic targets that interact with NAD were identified, that have regulatory and signalling functions in cancer and neurodegenerative diseases.<\/jats:p>","DOI":"10.1515\/jib-2022-0049","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T11:23:21Z","timestamp":1678188201000},"source":"Crossref","is-referenced-by-count":7,"title":["Study of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic target"],"prefix":"10.1515","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5244-068X","authenticated-orcid":false,"given":"Sara","family":"Duarte-Pereira","sequence":"first","affiliation":[{"name":"IEETA\/DETI , University of Aveiro , Aveiro , Portugal"},{"name":"Department of Medical Sciences , iBiMED \u2013 Institute of Biomedicine, University of Aveiro , Aveiro , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-3983","authenticated-orcid":false,"given":"S\u00e9rgio","family":"Matos","sequence":"additional","affiliation":[{"name":"IEETA\/DETI , University of Aveiro , Aveiro , Portugal"},{"name":"LASI \u2013 Intelligent Systems Associate Laboratory , Guimar\u00e3es , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6672-6176","authenticated-orcid":false,"given":"Jos\u00e9 Lu\u00eds","family":"Oliveira","sequence":"additional","affiliation":[{"name":"IEETA\/DETI , University of Aveiro , Aveiro , Portugal"},{"name":"LASI \u2013 Intelligent Systems Associate Laboratory , Guimar\u00e3es , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-8042","authenticated-orcid":false,"given":"Raquel M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences , iBiMED \u2013 Institute of Biomedicine, University of Aveiro , Aveiro , Portugal"},{"name":"Universidade Cat\u00f3lica Portuguesa, Faculty of Dental Medicine, Center for Interdisciplinary Research in Health (CIIS) , Viseu , Portugal"}]}],"member":"374","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"2023073113214253456_j_jib-2022-0049_ref_001","doi-asserted-by":"crossref","unstructured":"Haigis, MC, Sinclair, DA. 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