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They regulate epidermal growth factor receptor signalling in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    by releasing signalling ligands from their transmembrane tethers. Their functions in mammals are poorly understood, in part because of the lack of endogenous substrates identified thus far. We used a quantitative proteomics approach to investigate the substrate repertoire of rhomboid protease RHBDL2 in human cells. We reveal a range of novel substrates that are specifically cleaved by RHBDL2, including the interleukin-6 receptor (IL6R), cell surface protease inhibitor Spint-1, the collagen receptor tyrosine kinase DDR1, N-Cadherin, CLCP1\/DCBLD2, KIRREL, BCAM and others. We further demonstrate that these substrates can be shed by endogenously expressed RHBDL2 and that a subset of them is resistant to shedding by cell surface metalloproteases. The expression profiles and identity of the substrates implicate RHBDL2 in physiological or pathological processes affecting epithelial homeostasis.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-07556-3","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T05:43:23Z","timestamp":1501479803000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis"],"prefix":"10.1038","volume":"7","author":[{"given":"Nicholas","family":"Johnson","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2076-9891","authenticated-orcid":false,"given":"Jana","family":"B\u0159ezinov\u00e1","sequence":"additional","affiliation":[]},{"given":"Elaine","family":"Stephens","sequence":"additional","affiliation":[]},{"given":"Emma","family":"Burbridge","sequence":"additional","affiliation":[]},{"given":"Matthew","family":"Freeman","sequence":"additional","affiliation":[]},{"given":"Colin","family":"Adrain","sequence":"additional","affiliation":[]},{"given":"Kvido","family":"Strisovsky","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"7556_CR1","doi-asserted-by":"publisher","first-page":"4277","DOI":"10.1093\/emboj\/cdf434","volume":"21","author":"S Urban","year":"2002","unstructured":"Urban, S., Lee, J. 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