{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:21:24Z","timestamp":1784132484150,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD024794"],"award-info":[{"award-number":["OD024794"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD028242"],"award-info":[{"award-number":["OD028242"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The functionally diverse members of the human Transforming Growth Factor-\u03b2 (TGF-\u03b2) family are tightly regulated. TGF-\u03b2 regulation includes 2 disulfide-dependent mechanisms\u2014dimerization and partner protein binding. The specific cysteines participating in these regulatory mechanisms are known in just 3 of the 33 human TGF-\u03b2 proteins. Human prodomain alignments revealed that 24 TGF-\u03b2 prodomains contain conserved cysteines in 2 highly exposed locations. There are 3 in the region of the \u03b28 helix that mediates dimerization near the prodomain carboxy terminus. There are 2 in the Association region that mediates partner protein binding near the prodomain amino terminus. The alignments predict the specific cysteines contributing to disulfide-dependent regulation of 72% of human TGF-\u03b2 proteins. Database mining then identified 9 conserved prodomain cysteine mutations and their disease phenotypes in 7 TGF-\u03b2 proteins. Three common adenoma phenotypes for prodomain cysteine mutations suggested 7 new regulatory heterodimer pairs. Two common adenoma phenotypes for prodomain and binding partner cysteine mutations revealed 17 new regulatory interactions. Overall, the analysis of human TGF-\u03b2 prodomains suggests a significantly expanded scope of disulfide-dependent regulation by heterodimerization and partner protein binding; regulation that is often lost in tumors.<\/jats:p>","DOI":"10.1093\/g3journal\/jkac271","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T20:09:42Z","timestamp":1665432582000},"source":"Crossref","is-referenced-by-count":3,"title":["Computational analysis of prodomain cysteines in human TGF-\u03b2 proteins reveals frequent loss of disulfide-dependent regulation in tumors"],"prefix":"10.1093","volume":"12","author":[{"given":"Samantha M","family":"Daly","sequence":"first","affiliation":[{"name":"School of Life Sciences, Arizona State University , Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Peraza","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University , Tempe, AZ 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