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The disease is almost always caused by variations in the polycystic kidney and hepatic disease 1 gene, which encodes fibrocystin (FC), a very large, single\u2010pass transmembrane glycoprotein found in primary cilia, urine and urinary exosomes. By comparison to proteins involved in autosomal dominant PKD, our structural and molecular understanding of FC has lagged far behind such that there are no published experimentally determined structures of any part of the protein. Bioinformatics analyses predict that the ectodomain contains a long chain of immunoglobulin\u2010like plexin\u2010transcription factor domains, a protective antigen 14 domain, a tandem G8\u2010TMEM2 homology region and a sperm protein, enterokinase and agrin domain. Here we review current knowledge on the molecular function of the protein from a structural perspective.<\/jats:p>","DOI":"10.1111\/ahg.12535","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T07:25:38Z","timestamp":1698737138000},"page":"58-75","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The molecular structure and function of fibrocystin, the key gene product implicated in autosomal recessive polycystic kidney disease (ARPKD)"],"prefix":"10.1111","volume":"88","author":[{"given":"Travis A K","family":"Bannell","sequence":"first","affiliation":[{"name":"Astbury Centre for Structural and Molecular Biology University of Leeds  Leeds UK"},{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-1436","authenticated-orcid":false,"given":"Joseph J B","family":"Cockburn","sequence":"additional","affiliation":[{"name":"Astbury Centre for Structural and Molecular Biology University of Leeds  Leeds UK"},{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000200165.90373.9a"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010111173"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72316"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2706-2"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20029"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00148.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1185-7"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.04.019"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43488-w"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12595"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2634-1"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-002-1021-0"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-014-2887-3"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041912"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr588"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121674"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496473"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00167.2018"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.10.031"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16014"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.06.017"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3046.2003.00094.x"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2006.00292.x"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.440"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq7317"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0143-6"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.01.004"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.371567"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.371880"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200910096"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.04.008"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000078805.87038.05"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070381"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm141"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00427-15"},{"issue":"1","key":"e_1_2_13_37_1","first-page":"F3","article-title":"Polycystic kidney disease: A predominance of giant nephrons","volume":"244","author":"Grantham J. 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