{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:27:32Z","timestamp":1791624452824,"version":"4.3.4"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T00:00:00Z","timestamp":1463097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T00:00:00Z","timestamp":1463097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.<\/jats:p>","DOI":"10.1038\/ncomms11491","type":"journal-article","created":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T10:34:39Z","timestamp":1463135679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":246,"title":["An organelle-specific protein landscape identifies novel diseases and molecular mechanisms"],"prefix":"10.1038","volume":"7","author":[{"given":"Karsten","family":"Boldt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0658-4399","authenticated-orcid":false,"given":"Jeroen","family":"van Reeuwijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Koutroumpas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh-Minh T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Texier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E. C.","family":"van Beersum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Willer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorus A.","family":"Mans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Dougherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ideke J. C.","family":"Lamers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlien L. M.","family":"Coene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen H.","family":"Arts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Betts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"Bolat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Johannes","family":"Gloeckner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khatera","family":"Haidari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette","family":"Hetterschijt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Iaconis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagan","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Klose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Knapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Latour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stef J. F.","family":"Letteboer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo L.","family":"Marcelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Mitic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Morleo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machteld M.","family":"Oud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moniek","family":"Riemersma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulien A.","family":"Terhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grischa","family":"Toedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teunis J. P.","family":"van Dam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"de Vrieze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Wissinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Man","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordana","family":"Apic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Beales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver E.","family":"Blacque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby J.","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn A.","family":"Huynen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Katsanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannie","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heymut","family":"Omran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"van Wijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Wolfrum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Kepes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica E.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunella","family":"Franco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9133-2008","authenticated-orcid":false,"given":"Rachel H.","family":"Giles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Ueffing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1905-4717","authenticated-orcid":false,"given":"Robert B.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Roepman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UK10K Rare Diseases Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Al-Turki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinu","family":"Antony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Barroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Bentham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoumo","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keren","family":"Carss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebahattin","family":"Cirak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Cosgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Danecek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Durbin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fitzpatrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Floyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Reghan Foley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Futema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve E.","family":"Humphries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Hurles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Joyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Mitchison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Muddyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"O'Rahilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Onoufriadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicity","family":"Payne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Plagnol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Savage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Scambler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Schmidts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Schoenmakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Semple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Stalker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margriet","family":"van Kogelenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parthiban","family":"Vijayarangakannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ros","family":"Whittall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,13]]},"reference":[{"key":"BFncomms11491_CR1","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.cell.2015.04.013","volume":"161","author":"N Sahni","year":"2015","unstructured":"Sahni, N. et al. Widespread macromolecular interaction perturbations in human genetic disorders. Cell 161, 647\u2013660 (2015).","journal-title":"Cell"},{"key":"BFncomms11491_CR2","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.cell.2015.08.056","volume":"163","author":"P Creixell","year":"2015","unstructured":"Creixell, P. et al. Kinome-wide decoding of network-attacking mutations rewiring cancer signaling. Cell 163, 202\u2013217 (2015).","journal-title":"Cell"},{"key":"BFncomms11491_CR3","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1126\/science.1176343","volume":"326","author":"S K\u00fchner","year":"2009","unstructured":"K\u00fchner, S. et al. Proteome organization in a genome-reduced bacterium. Science 326, 1235\u20131240 (2009).","journal-title":"Science"},{"key":"BFncomms11491_CR4","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1002\/dvdy.21540","volume":"237","author":"N Santos","year":"2008","unstructured":"Santos, N. & Reiter, J. F. Building it up and taking it down: the regulation of vertebrate ciliogenesis. Dev. Dyn. 237, 1972\u20131981 (2008).","journal-title":"Dev. Dyn."},{"key":"BFncomms11491_CR5","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1056\/NEJMra1010172","volume":"364","author":"RS Schwartz","year":"2011","unstructured":"Schwartz, R. S., Hildebrandt, F., Benzing, T. & Katsanis, N. Ciliopathies. N. Engl. J. Med. 364, 1533\u20131543 (2011).","journal-title":"N. Engl. J. Med."},{"key":"BFncomms11491_CR6","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1007\/s00467-010-1731-7","volume":"26","author":"AM Waters","year":"2011","unstructured":"Waters, A. M. & Beales, P. L. Ciliopathies: an expanding disease spectrum. Pediatr. Nephrol. 26, 1039\u20131056 (2011).","journal-title":"Pediatr. Nephrol."},{"key":"BFncomms11491_CR7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1126\/science.1124534","volume":"313","author":"V Singla","year":"2006","unstructured":"Singla, V. The primary cilium as the cell\u2019s antenna: signaling at a sensory organelle. Science 313, 629\u2013633 (2006).","journal-title":"Science"},{"key":"BFncomms11491_CR8","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/ng0906-961","volume":"38","author":"A Gherman","year":"2006","unstructured":"Gherman, A., Davis, E. E. & Katsanis, N. The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat. Genet. 38, 961\u2013962 (2006).","journal-title":"Nat. Genet."},{"key":"BFncomms11491_CR9","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.devcel.2015.10.015","volume":"35","author":"DU Mick","year":"2015","unstructured":"Mick, D. U. et al. Proteomics of primary cilia by proximity labeling. Dev. Cell 35, 497\u2013512 (2015).","journal-title":"Dev. Cell"},{"key":"BFncomms11491_CR10","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.1002\/pmic.200700038","volume":"7","author":"CJ Gloeckner","year":"2007","unstructured":"Gloeckner, C. J., Boldt, K., Schumacher, A., Roepman, R. & Ueffing, M. A novel tandem affinity purification strategy for the efficient isolation and characterisation of native protein complexes. Proteomics 7, 4228\u20134234 (2007).","journal-title":"Proteomics"},{"key":"BFncomms11491_CR11","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1172\/JCI45627","volume":"121","author":"K Boldt","year":"2011","unstructured":"Boldt, K. et al. Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice. J. Clin. Invest. 121, 2169\u20132180 (2011).","journal-title":"J. Clin. Invest."},{"key":"BFncomms11491_CR12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/2046-2530-2-7","volume":"2","author":"TJ van Dam","year":"2013","unstructured":"van Dam, T. J., Wheway, G., Slaats, G. G., Huynen, M. A. & Giles, R. H. The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium. Cilia 2, 7 (2013).","journal-title":"Cilia"},{"key":"BFncomms11491_CR13","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/nature04532","volume":"440","author":"A-C Gavin","year":"2006","unstructured":"Gavin, A.-C. et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631\u2013636 (2006).","journal-title":"Nature"},{"key":"BFncomms11491_CR14","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.ymeth.2012.07.028","volume":"58","author":"LG Trabuco","year":"2012","unstructured":"Trabuco, L. G., Betts, M. J. & Russell, R. B. Negative protein-protein interaction datasets derived from large-scale two-hybrid experiments. Methods 58, 343\u2013348 (2012).","journal-title":"Methods"},{"key":"BFncomms11491_CR15","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1002\/pmic.201400441","volume":"15","author":"M Wang","year":"2015","unstructured":"Wang, M., Herrmann, C. J., Simonovic, M., Szklarczyk, D. & von Mering, C. Version 4.0 of PaxDb: Protein abundance data, integrated across model organisms, tissues, and cell-lines. Proteomics 15, 3163\u20133168 (2015).","journal-title":"Proteomics"},{"key":"BFncomms11491_CR16","doi-asserted-by":"publisher","first-page":"8666","DOI":"10.1038\/ncomms9666","volume":"6","author":"AA Bizet","year":"2015","unstructured":"Bizet, A. A. et al. Mutations in TRAF3IP1\/IFT54 reveal a new role for IFT proteins in microtubule stabilization. Nat. Commun. 6, 8666 (2015).","journal-title":"Nat. Commun."},{"key":"BFncomms11491_CR17","doi-asserted-by":"publisher","first-page":"51743","DOI":"10.1074\/jbc.M308702200","volume":"278","author":"S Moskalenko","year":"2003","unstructured":"Moskalenko, S. et al. Ral GTPases regulate exocyst assembly through dual subunit interactions. J. Biol. Chem. 278, 51743\u201351748 (2003).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11491_CR18","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s10495-007-0176-3","volume":"13","author":"G Gdynia","year":"2008","unstructured":"Gdynia, G. et al. BLOC1S2 interacts with the HIPPI protein and sensitizes NCH89 glioblastoma cells to apoptosis. Apoptosis 13, 437\u2013447 (2008).","journal-title":"Apoptosis"},{"key":"BFncomms11491_CR19","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.cell.2011.04.019","volume":"145","author":"L Sang","year":"2011","unstructured":"Sang, L. et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 145, 513\u2013528 (2011).","journal-title":"Cell"},{"key":"BFncomms11491_CR20","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.devcel.2009.12.014","volume":"18","author":"HW Ko","year":"2010","unstructured":"Ko, H. W. et al. Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction. Dev. Cell 18, 237\u2013247 (2010).","journal-title":"Dev. Cell"},{"key":"BFncomms11491_CR21","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/embj.201488175","volume":"33","author":"T Chaya","year":"2014","unstructured":"Chaya, T., Omori, Y., Kuwahara, R. & Furukawa, T. ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport. EMBO J. 33, 1227\u20131242 (2014).","journal-title":"EMBO J."},{"key":"BFncomms11491_CR22","doi-asserted-by":"publisher","first-page":"e75217","DOI":"10.1371\/journal.pone.0075217","volume":"8","author":"O Francis","year":"2013","unstructured":"Francis, O., Han, F. & Adams, J. C. Molecular phylogeny of a RING E3 ubiquitin ligase, conserved in eukaryotic cells and dominated by homologous components, the muskelin\/RanBPM\/CTLH complex. PLoS ONE 8, e75217 (2013).","journal-title":"PLoS ONE"},{"key":"BFncomms11491_CR23","doi-asserted-by":"publisher","first-page":"5081","DOI":"10.1038\/ncomms6081","volume":"5","author":"K Kasahara","year":"2014","unstructured":"Kasahara, K. et al. Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension. Nat. Commun. 5, 5081 (2014).","journal-title":"Nat. Commun."},{"key":"BFncomms11491_CR24","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1038\/ncb3201","volume":"17","author":"G Wheway","year":"2015","unstructured":"Wheway, G. et al. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nat. Cell Biol. 17, 1074\u20131087 (2015).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms11491_CR25","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/nature14962","volume":"526","author":"K Walter","year":"2015","unstructured":"Walter, K. et al. The UK10K project identifies rare variants in health and disease. Nature 526, 82\u201390 (2015).","journal-title":"Nature"},{"key":"BFncomms11491_CR26","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1083\/jcb.141.4.993","volume":"141","author":"DG Cole","year":"1998","unstructured":"Cole, D. G. et al. Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J. Cell Biol. 141, 993\u20131008 (1998).","journal-title":"J. Cell Biol."},{"key":"BFncomms11491_CR27","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/cm.20346","volume":"66","author":"JA Follit","year":"2009","unstructured":"Follit, J. A., Xu, F., Keady, B. T. & Pazour, G. J. Characterization of mouse IFT complex B. Cell Motil. Cytoskeleton 66, 457\u2013468 (2009).","journal-title":"Cell Motil. Cytoskeleton"},{"key":"BFncomms11491_CR28","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cell.2014.05.039","volume":"158","author":"M Taipale","year":"2014","unstructured":"Taipale, M. et al. A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 158, 434\u2013448 (2014).","journal-title":"Cell"},{"key":"BFncomms11491_CR29","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1073\/pnas.0910268107","volume":"107","author":"S Seo","year":"2010","unstructured":"Seo, S. et al. BBS6, BBS10, and BBS12 form a complex with CCT\/TRiC family chaperonins and mediate BBSome assembly. Proc. Natl Acad. Sci. USA 107, 1488\u20131493 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms11491_CR30","doi-asserted-by":"publisher","first-page":"27688","DOI":"10.1074\/jbc.M505062200","volume":"280","author":"BF Lucker","year":"2005","unstructured":"Lucker, B. F. et al. Characterization of the intraflagellar transport complex B core: direct interaction of the IFT81 and IFT74\/72 subunits. J. Biol. Chem. 280, 27688\u201327696 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11491_CR31","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1074\/mcp.O113.033233","volume":"13","author":"Y Texier","year":"2014","unstructured":"Texier, Y. et al. Elution profile analysis of SDS-induced subcomplexes by quantitative mass spectrometry. Mol. Cell. Proteomics 13, 1382\u20131391 (2014).","journal-title":"Mol. Cell. Proteomics"},{"key":"BFncomms11491_CR32","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1093\/nar\/gku1094","volume":"43","author":"MJ Betts","year":"2014","unstructured":"Betts, M. J. et al. Mechismo: predicting the mechanistic impact of mutations and modifications on molecular interactions. Nucleic Acids Res. 43, e10 (2014).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms11491_CR33","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.tibs.2010.04.003","volume":"35","author":"CU Stirnimann","year":"2010","unstructured":"Stirnimann, C. U., Petsalaki, E., Russell, R. B. & M\u00fcller, C. W. WD40 proteins propel cellular networks. Trends Biochem. Sci. 35, 565\u2013574 (2010).","journal-title":"Trends Biochem. Sci."},{"key":"BFncomms11491_CR34","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.tig.2010.01.006","volume":"26","author":"NA Zaghloul","year":"2010","unstructured":"Zaghloul, N. A. & Katsanis, N. Functional modules, mutational load and human genetic disease. Trends Genet. 26, 168\u2013176 (2010).","journal-title":"Trends Genet."},{"key":"BFncomms11491_CR35","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1083\/jcb.200911095","volume":"189","author":"T Sedmak","year":"2010","unstructured":"Sedmak, T. & Wolfrum, U. Intraflagellar transport molecules in ciliary and nonciliary cells of the retina. J. Cell Biol. 189, 171\u2013186 (2010).","journal-title":"J. Cell Biol."},{"key":"BFncomms11491_CR36","doi-asserted-by":"publisher","first-page":"6943","DOI":"10.1073\/pnas.1221011110","volume":"110","author":"TJP van Dam","year":"2013","unstructured":"van Dam, T. J. P. et al. Evolution of modular intraflagellar transport from a coatomer-like progenitor. Proc. Natl Acad. Sci. USA 110, 6943\u20136948 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms11491_CR37","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.1073\/pnas.1018823108","volume":"108","author":"CJ Westlake","year":"2011","unstructured":"Westlake, C. J. et al. Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome. Proc. Natl Acad. Sci. USA 108, 2759\u20132764 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms11491_CR38","doi-asserted-by":"publisher","first-page":"23699","DOI":"10.1074\/jbc.M310546200","volume":"279","author":"E Umlauf","year":"2004","unstructured":"Umlauf, E. et al. Association of stomatin with lipid bodies. J. Biol. Chem. 279, 23699\u201323709 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11491_CR39","doi-asserted-by":"publisher","first-page":"35958","DOI":"10.1074\/jbc.M313778200","volume":"279","author":"S Wang","year":"2004","unstructured":"Wang, S. et al. The mammalian exocyst, a complex required for exocytosis, inhibits tubulin polymerization. J. Biol. Chem. 279, 35958\u201335966 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11491_CR40","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/0-387-32442-9_49","volume":"572","author":"J Reiners","year":"2006","unstructured":"Reiners, J. & Wolfrum, U. Molecular analysis of the supramolecular usher protein complex in the retina. Harmonin as the key protein of the Usher syndrome. Adv. Exp. Med. Biol. 572, 349\u2013353 (2006).","journal-title":"Adv. Exp. Med. Biol."},{"key":"BFncomms11491_CR41","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.tibs.2008.09.004","volume":"33","author":"N Wei","year":"2008","unstructured":"Wei, N., Serino, G. & Deng, X.-W. The COP9 signalosome: more than a protease. Trends Biochem. Sci. 33, 592\u2013600 (2008).","journal-title":"Trends Biochem. Sci."},{"key":"BFncomms11491_CR42","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.cell.2015.06.043","volume":"162","author":"EL Huttlin","year":"2015","unstructured":"Huttlin, E. L. et al. The BioPlex network: a systematic exploration of the human interactome. Cell 162, 425\u2013440 (2015).","journal-title":"Cell"},{"key":"BFncomms11491_CR43","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.cell.2015.09.053","volume":"163","author":"MY Hein","year":"2015","unstructured":"Hein, M. Y. et al. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 163, 712\u2013723 (2015).","journal-title":"Cell"},{"key":"BFncomms11491_CR44","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.molcel.2014.03.047","volume":"54","author":"J Yan","year":"2014","unstructured":"Yan, J. et al. The 3M complex maintains microtubule and genome integrity. Mol. Cell 54, 791\u2013804 (2014).","journal-title":"Mol. Cell"},{"key":"BFncomms11491_CR45","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/ng1628","volume":"37","author":"C Huber","year":"2005","unstructured":"Huber, C. et al. Identification of mutations in CUL7 in 3-M syndrome. Nat. Genet. 37, 1119\u20131124 (2005).","journal-title":"Nat. Genet."},{"key":"BFncomms11491_CR46","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13630-015-0017-x","volume":"4","author":"H Ajzenberg","year":"2015","unstructured":"Ajzenberg, H. et al. Non-invasive sources of cells with primary cilia from pediatric and adult patients. Cilia 4, 8 (2015).","journal-title":"Cilia"},{"key":"BFncomms11491_CR47","doi-asserted-by":"publisher","first-page":"773","DOI":"10.15252\/embj.201593164","volume":"35","author":"M Taschner","year":"2016","unstructured":"Taschner, M. et al. Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin-binding IFT-B2 complex. EMBO J. 35, 773\u2013790 (2016).","journal-title":"EMBO J."},{"key":"BFncomms11491_CR48","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/msb.2009.80","volume":"5","author":"Q Zhong","year":"2009","unstructured":"Zhong, Q. et al. Edgetic perturbation models of human inherited disorders. Mol. Syst. Biol. 5, 321 (2009).","journal-title":"Mol. Syst. Biol."},{"key":"BFncomms11491_CR49","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1006\/meth.1997.0475","volume":"12","author":"N Tanese","year":"1997","unstructured":"Tanese, N. Small-scale density gradient sedimentation to separate and analyze multiprotein complexes. Methods 12, 224\u2013234 (1997).","journal-title":"Methods"},{"key":"BFncomms11491_CR50","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0091-679X(08)91009-8","volume":"91","author":"K Boldt","year":"2009","unstructured":"Boldt, K., van Reeuwijk, J., Gloeckner, C. J., Ueffing, M. & Roepman, R. Tandem affinity purification of ciliopathy-associated protein complexes. Methods Cell Biol. 91, 143\u2013160 (2009).","journal-title":"Methods Cell Biol."},{"key":"BFncomms11491_CR51","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1074\/mcp.T500030-MCP200","volume":"4","author":"JV Olsen","year":"2005","unstructured":"Olsen, J. V et al. Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol. Cell. Proteomics 4, 2010\u20132021 (2005).","journal-title":"Mol. Cell. Proteomics"},{"key":"BFncomms11491_CR52","doi-asserted-by":"publisher","first-page":"5383","DOI":"10.1021\/ac025747h","volume":"74","author":"A Keller","year":"2002","unstructured":"Keller, A., Nesvizhskii, A. I., Kolker, E. & Aebersold, R. Empirical statistical model to estimate the accuracy of peptide identifications made by MS\/MS and database search. Anal. Chem. 74, 5383\u20135392 (2002).","journal-title":"Anal. Chem."},{"key":"BFncomms11491_CR53","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1021\/ac0341261","volume":"75","author":"AI Nesvizhskii","year":"2003","unstructured":"Nesvizhskii, A. I., Keller, A., Kolker, E. & Aebersold, R. A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646\u20134658 (2003).","journal-title":"Anal. Chem."},{"key":"BFncomms11491_CR54","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","volume":"26","author":"J Cox","year":"2008","unstructured":"Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367\u20131372 (2008).","journal-title":"Nat. Biotechnol."},{"key":"BFncomms11491_CR55","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nmeth.1931","volume":"9","author":"S Orchard","year":"2012","unstructured":"Orchard, S. et al. Protein interaction data curation: the International Molecular Exchange (IMEx) consortium. Nat. Methods 9, 345\u2013350 (2012).","journal-title":"Nat. Methods"},{"key":"BFncomms11491_CR56","doi-asserted-by":"publisher","first-page":"W155","DOI":"10.1093\/nar\/gkq331","volume":"38","author":"R C\u00f4t\u00e9","year":"2010","unstructured":"C\u00f4t\u00e9, R. et al. The ontology lookup service: bigger and better. Nucleic Acids Res. 38, W155\u2013W160 (2010).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms11491_CR57","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1214\/aos\/1176342871","volume":"2","author":"CE Antoniak","year":"1974","unstructured":"Antoniak, C. E. Mixtures of Dirichlet processes with applications to bayesian nonparametric problems. Ann. Stat. 2, 1152\u20131174 (1974).","journal-title":"Ann. Stat."},{"key":"BFncomms11491_CR58","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1214\/06-BA104","volume":"1","author":"DM Blei","year":"2006","unstructured":"Blei, D. M. & Jordan, M. I. Variational inference for Dirichlet process mixtures. Bayesian Anal. 1, 121\u2013143 (2006).","journal-title":"Bayesian Anal."},{"key":"BFncomms11491_CR59","doi-asserted-by":"publisher","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","volume":"5","author":"RC Gentleman","year":"2004","unstructured":"Gentleman, R. C. et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).","journal-title":"Genome Biol."},{"key":"BFncomms11491_CR60","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/ng.756","volume":"43","author":"EE Davis","year":"2011","unstructured":"Davis, E. E. et al. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat. Genet. 43, 189\u2013196 (2011).","journal-title":"Nat. Genet."},{"key":"BFncomms11491_CR61","doi-asserted-by":"publisher","first-page":"D290","DOI":"10.1093\/nar\/gkr1065","volume":"40","author":"M Punta","year":"2012","unstructured":"Punta, M. et al. The Pfam protein families database. Nucleic Acids Res. 40, D290\u2013D301 (2012).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms11491_CR62","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-8-2","volume":"8","author":"MR Karpenahalli","year":"2007","unstructured":"Karpenahalli, M. R., Lupas, A. N. & S\u00f6ding, J. TPRpred: a tool for prediction of TPR-, PPR- and SEL1-like repeats from protein sequences. BMC Bioinformatics 8, 2 (2007).","journal-title":"BMC Bioinformatics"},{"key":"BFncomms11491_CR63","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/prot.340140216","volume":"14","author":"RB Russell","year":"1992","unstructured":"Russell, R. B. & Barton, G. J. Multiple protein sequence alignment from tertiary structure comparison: assignment of global and residue confidence levels. Proteins 14, 309\u2013323 (1992).","journal-title":"Proteins"},{"key":"BFncomms11491_CR64","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1074\/mcp.M800113-MCP200","volume":"7","author":"SC Bendall","year":"2008","unstructured":"Bendall, S. C. et al. Prevention of amino acid conversion in SILAC experiments with embryonic stem cells. Mol. Cell. Proteomics 7, 1587\u20131597 (2008).","journal-title":"Mol. Cell. Proteomics"},{"key":"BFncomms11491_CR65","doi-asserted-by":"publisher","first-page":"19.20.1","DOI":"10.1002\/0471140864.ps1920s57","volume":"57","author":"CJ Gloeckner","year":"2009","unstructured":"Gloeckner, C. J., Boldt, K. & Ueffing, M. Strep\/FLAG tandem affinity purification (SF-TAP) to study protein interactions. Curr. Protoc. Protein Sci. 57, 19.20.1\u201319.20.19 (2009).","journal-title":"Curr. Protoc. Protein Sci."},{"key":"BFncomms11491_CR66","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-59745-398-1_10","volume":"484","author":"SJF Letteboer","year":"2008","unstructured":"Letteboer, S. J. F. & Roepman, R. Versatile screening for binary protein-protein interactions by yeast two-hybrid mating. Methods Mol. Biol. 484, 145\u2013159 (2008).","journal-title":"Methods Mol. Biol."},{"key":"BFncomms11491_CR67","doi-asserted-by":"publisher","first-page":"5174","DOI":"10.1093\/hmg\/dds368","volume":"21","author":"SA Di Gioia","year":"2012","unstructured":"Di Gioia, S. A. et al. FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies. Hum. Mol. Genet. 21, 5174\u20135184 (2012).","journal-title":"Hum. Mol. Genet."},{"key":"BFncomms11491_CR68","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/bioinformatics\/btq330","volume":"26","author":"W McLaren","year":"2010","unstructured":"McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP effect predictor. Bioinformatics 26, 2069\u20132070 (2010).","journal-title":"Bioinformatics"},{"key":"BFncomms11491_CR69","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature11632","volume":"491","author":"GR Abecasis","year":"2012","unstructured":"Abecasis, G. R. et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56\u201365 (2012).","journal-title":"Nature"},{"key":"BFncomms11491_CR70","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.ajhg.2011.05.028","volume":"89","author":"D Hanson","year":"2011","unstructured":"Hanson, D. et al. Exome sequencing identifies CCDC8 mutations in 3-M syndrome, suggesting that CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth. Am. J. Hum. Genet. 89, 148\u2013153 (2011).","journal-title":"Am. J. Hum. Genet."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms11491.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11491","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11491.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T11:31:08Z","timestamp":1672831868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms11491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,13]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,1]]}},"alternative-id":["BFncomms11491"],"URL":"https:\/\/doi.org\/10.1038\/ncomms11491","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,13]]},"assertion":[{"value":"15 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11491"}}