ID OFD1_HUMAN Reviewed; 1012 AA. AC O75665; B9ZVU5; O75666; Q4VAK4; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 201. DE RecName: Full=Centriole and centriolar satellite protein OFD1 {ECO:0000305}; DE AltName: Full=Oral-facial-digital syndrome 1 protein; DE AltName: Full=Protein 71-7A; GN Name=OFD1; Synonyms=CXorf5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RX PubMed=9722947; DOI=10.1006/geno.1998.5348; RA de Conciliis L., Marchitiello A., Wapenaar M.C., Borsani G., Giglio S., RA Mariani M., Consalez G.G., Zuffardi O., Franco B., Ballabio A., Banfi S.; RT "Characterization of Cxorf5 (71-7A), a novel human cDNA mapping to Xp22 and RT encoding a protein containing coiled-coil alpha-helical domains."; RL Genomics 51:243-250(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 734-744, FUNCTION, INTERACTION WITH TBC1D31, RP PHOSPHORYLATION AT SER-735 BY PKA, UBIQUITINATION BY PJA2, AND MUTAGENESIS RP OF GLU-97 AND SER-735. RX PubMed=33934390; DOI=10.15252/embj.2020106503; RA Senatore E., Chiuso F., Rinaldi L., Intartaglia D., Delle Donne R., RA Pedone E., Catalanotti B., Pirone L., Fiorillo B., Moraca F., Giamundo G., RA Scala G., Raffeiner A., Torres-Quesada O., Stefan E., Kwiatkowski M., RA van Pijkeren A., Morleo M., Franco B., Garbi C., Conte I., Feliciello A.; RT "The TBC1D31/praja2 complex controls primary ciliogenesis through PKA- RT directed OFD1 ubiquitylation."; RL EMBO J. 40:e106503-e106503(2021). RN [5] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT OFD1 PHE-74. RX PubMed=12595504; DOI=10.1097/01.asn.0000054497.48394.d2; RA Romio L., Wright V., Price K., Winyard P.J., Donnai D., Porteous M.E., RA Franco B., Giorgio G., Malcolm S., Woolf A.S., Feather S.A.; RT "OFD1, the gene mutated in oral-facial-digital syndrome type 1, is RT expressed in the metanephros and in human embryonic renal mesenchymal RT cells."; RL J. Am. Soc. Nephrol. 14:680-689(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE RP ANALYSIS]. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [7] RP INVOLVEMENT IN SGBS2. RX PubMed=16783569; DOI=10.1007/s00439-006-0210-5; RA Budny B., Chen W., Omran H., Fliegauf M., Tzschach A., Wisniewska M., RA Jensen L.R., Raynaud M., Shoichet S.A., Badura M., Lenzner S., RA Latos-Bielenska A., Ropers H.-H.; RT "A novel X-linked recessive mental retardation syndrome comprising RT macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type RT I syndrome."; RL Hum. Genet. 120:171-178(2006). RN [8] RP SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, AND INTERACTION WITH RUVBL1. RX PubMed=17761535; DOI=10.1091/mbc.e07-03-0198; RA Giorgio G., Alfieri M., Prattichizzo C., Zullo A., Cairo S., Franco B.; RT "Functional characterization of the OFD1 protein reveals a nuclear RT localization and physical interaction with subunits of a chromatin RT remodeling complex."; RL Mol. Biol. Cell 18:4397-4404(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP INVOLVEMENT IN JBTS10, AND INTERACTION WITH LCA5. RX PubMed=19800048; DOI=10.1016/j.ajhg.2009.09.002; RA Coene K.L., Roepman R., Doherty D., Afroze B., Kroes H.Y., Letteboer S.J., RA Ngu L.H., Budny B., van Wijk E., Gorden N.T., Azhimi M., RA Thauvin-Robinet C., Veltman J.A., Boink M., Kleefstra T., Cremers F.P., RA van Bokhoven H., de Brouwer A.P.; RT "OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5- RT encoded lebercilin."; RL Am. J. Hum. Genet. 85:465-481(2009). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=20230748; DOI=10.1016/j.devcel.2009.12.022; RA Singla V., Romaguera-Ros M., Garcia-Verdugo J.M., Reiter J.F.; RT "Ofd1, a human disease gene, regulates the length and distal structure of RT centrioles."; RL Dev. Cell 18:410-424(2010). RN [12] RP INTERACTION WITH SDCCAG8. RX PubMed=20835237; DOI=10.1038/ng.662; RA Otto E.A., Hurd T.W., Airik R., Chaki M., Zhou W., Stoetzel C., Patil S.B., RA Levy S., Ghosh A.K., Murga-Zamalloa C.A., van Reeuwijk J., Letteboer S.J., RA Sang L., Giles R.H., Liu Q., Coene K.L., Estrada-Cuzcano A., Collin R.W., RA McLaughlin H.M., Held S., Kasanuki J.M., Ramaswami G., Conte J., Lopez I., RA Washburn J., Macdonald J., Hu J., Yamashita Y., Maher E.R., RA Guay-Woodford L.M., Neumann H.P., Obermuller N., Koenekoop R.K., RA Bergmann C., Bei X., Lewis R.A., Katsanis N., Lopes V., Williams D.S., RA Lyons R.H., Dang C.V., Brito D.A., Dias M.B., Zhang X., Cavalcoli J.D., RA Nurnberg G., Nurnberg P., Pierce E.A., Jackson P.K., Antignac C., RA Saunier S., Roepman R., Dollfus H., Khanna H., Hildebrandt F.; RT "Candidate exome capture identifies mutation of SDCCAG8 as the cause of a RT retinal-renal ciliopathy."; RL Nat. Genet. 42:840-850(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663 AND SER-669, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [14] RP INVOLVEMENT IN RP23. RX PubMed=22619378; DOI=10.1093/hmg/dds194; RA Webb T.R., Parfitt D.A., Gardner J.C., Martinez A., Bevilacqua D., RA Davidson A.E., Zito I., Thiselton D.L., Ressa J.H., Apergi M., Schwarz N., RA Kanuga N., Michaelides M., Cheetham M.E., Gorin M.B., Hardcastle A.J.; RT "Deep intronic mutation in OFD1, identified by targeted genomic next- RT generation sequencing, causes a severe form of X-linked retinitis RT pigmentosa (RP23)."; RL Hum. Mol. Genet. 21:3647-3654(2012). RN [15] RP SUBCELLULAR LOCATION. RX PubMed=24121310; DOI=10.1038/emboj.2013.223; RA Villumsen B.H., Danielsen J.R., Povlsen L., Sylvestersen K.B., Merdes A., RA Beli P., Yang Y.G., Choudhary C., Nielsen M.L., Mailand N., RA Bekker-Jensen S.; RT "A new cellular stress response that triggers centriolar satellite RT reorganization and ciliogenesis."; RL EMBO J. 32:3029-3040(2013). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663; SER-669; SER-686; RP SER-720; SER-745; SER-774; SER-789 AND SER-811, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP INTERACTION WITH MAP1LC3B. RX PubMed=24089205; DOI=10.1038/nature12606; RA Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B., RA Zhong Q.; RT "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar RT satellites."; RL Nature 502:254-257(2013). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP INTERACTION WITH C2CD3. RX PubMed=24997988; DOI=10.1038/ng.3031; RA Thauvin-Robinet C., Lee J.S., Lopez E., Herranz-Perez V., Shida T., RA Franco B., Jego L., Ye F., Pasquier L., Loget P., Gigot N., Aral B., RA Lopes C.A., St-Onge J., Bruel A.L., Thevenon J., Gonzalez-Granero S., RA Alby C., Munnich A., Vekemans M., Huet F., Fry A.M., Saunier S., RA Riviere J.B., Attie-Bitach T., Garcia-Verdugo J.M., Faivre L., RA Megarbane A., Nachury M.V.; RT "The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator RT of centriole elongation."; RL Nat. Genet. 46:905-911(2014). RN [20] RP INTERACTION WITH CEP20; KIAA0753 AND PCM1, AND SUBCELLULAR LOCATION. RX PubMed=26643951; DOI=10.1093/hmg/ddv488; RA Chevrier V., Bruel A.L., Van Dam T.J., Franco B., Lo Scalzo M., Lembo F., RA Audebert S., Baudelet E., Isnardon D., Bole A., Borg J.P., Kuentz P., RA Thevenon J., Burglen L., Faivre L., Riviere J.B., Huynen M.A., Birnbaum D., RA Rosnet O., Thauvin-Robinet C.; RT "OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar RT satellites and centrosomes and is mutated in one individual with oral- RT facial-digital syndrome."; RL Hum. Mol. Genet. 25:497-513(2016). RN [21] RP VARIANTS OFD1 358-LYS--ASP-360 DELINS PHE-SER-TYR AND ARG-435. RX PubMed=11179005; DOI=10.1086/318802; RA Ferrante M.I., Giorgio G., Feather S.A., Bulfone A., Wright V., Ghiani M., RA Selicorni A., Gammaro L., Scolari F., Woolf A.S., Sylvie O., Le Marec B., RA Malcolm S., Winter R., Ballabio A., Franco B.; RT "Identification of the gene for oral-facial-digital type I syndrome."; RL Am. J. Hum. Genet. 68:569-576(2001). RN [22] RP VARIANT OFD1 THR-79. RX PubMed=11950863; DOI=10.1136/jmg.39.4.292; RA Rakkolainen A., Ala-Mello S., Kristo P., Orpana A., Jaervelae I.; RT "Four novel mutations in the OFD1 (Cxorf5) gene in Finnish patients with RT oral-facial-digital syndrome 1."; RL J. Med. Genet. 39:292-296(2002). RN [23] RP VARIANT OFD1 SER-138. RX PubMed=16397067; DOI=10.1136/jmg.2004.027672; RA Thauvin-Robinet C., Cossee M., Cormier-Daire V., Van Maldergem L., RA Toutain A., Alembik Y., Bieth E., Layet V., Parent P., David A., RA Goldenberg A., Mortier G., Heron D., Sagot P., Bouvier A.M., Huet F., RA Cusin V., Donzel A., Devys D., Teyssier J.R., Faivre L.; RT "Clinical, molecular, and genotype-phenotype correlation studies from 25 RT cases of oral-facial-digital syndrome type 1: a French and Belgian RT collaborative study."; RL J. Med. Genet. 43:54-61(2006). RN [24] RP VARIANT OFD1 ARG-141. RX PubMed=23033313; DOI=10.1002/humu.22224; RA Bisschoff I.J., Zeschnigk C., Horn D., Wellek B., Riess A., Wessels M., RA Willems P., Jensen P., Busche A., Bekkebraten J., Chopra M., Hove H.D., RA Evers C., Heimdal K., Kaiser A.S., Kunstmann E., Robinson K.L., Linne M., RA Martin P., McGrath J., Pradel W., Prescott K.E., Roesler B., Rudolf G., RA Siebers-Renelt U., Tyshchenko N., Wieczorek D., Wolff G., Dobyns W.B., RA Morris-Rosendahl D.J.; RT "Novel mutations including deletions of the entire OFD1 gene in 30 families RT with type 1 orofaciodigital syndrome: A study of the extensive clinical RT variability."; RL Hum. Mutat. 34:237-247(2013). RN [25] RP VARIANT JBTS10 ASP-307. RX PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009; RG Care4Rare Canada Consortium; RA Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H., RA Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A., RA Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B., RA Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C., RA Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M., RA Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K., RA Shalev S., Michaud J.L.; RT "Joubert Syndrome in French Canadians and Identification of Mutations in RT CEP104."; RL Am. J. Hum. Genet. 97:744-753(2015). CC -!- FUNCTION: Component of the centrioles controlling mother and daughter CC centrioles length. Recruits to the centriole IFT88 and centriole distal CC appendage-specific proteins including CEP164 (By similarity). Involved CC in the biogenesis of the cilium, a centriole-associated function. The CC cilium is a cell surface projection found in many vertebrate cells CC required to transduce signals important for development and tissue CC homeostasis (PubMed:33934390). Plays an important role in development CC by regulating Wnt signaling and the specification of the left-right CC axis. Only OFD1 localized at the centriolar satellites is removed by CC autophagy, which is an important step in the ciliogenesis regulation CC (By similarity). {ECO:0000250|UniProtKB:Q80Z25, CC ECO:0000269|PubMed:33934390}. CC -!- SUBUNIT: Homooligomer. Interacts with LCA5. Interacts with RUVBL1; the CC interaction is direct and may mediate interaction with the NuA4 histone CC acetyltransferase complex. Interacts with SDCCAG8; the interaction is CC direct. Interacts with MAP1LC3B. Interacts with C2CD3; OFD1 may act as CC a negative regulator of C2CD3. Forms a complex with KIAA0753/OFIP and CC CEP20/FOR20; the interaction with CEP20 is detected only in the CC presence of KIAA0753. Interacts with PCM1; this interaction may be CC mediated by KIAA0753/OFIP (PubMed:26643951). Interacts with TBC1D31; CC regulates OFD1 activity in cilium assembly (PubMed:33934390). CC {ECO:0000269|PubMed:17761535, ECO:0000269|PubMed:19800048, CC ECO:0000269|PubMed:20835237, ECO:0000269|PubMed:24089205, CC ECO:0000269|PubMed:24997988, ECO:0000269|PubMed:26643951, CC ECO:0000269|PubMed:33934390}. CC -!- INTERACTION: CC O75665; O75143: ATG13; NbExp=4; IntAct=EBI-716327, EBI-2798775; CC O75665; Q4AC94: C2CD3; NbExp=3; IntAct=EBI-716327, EBI-10897521; CC O75665; Q9GZQ8: MAP1LC3B; NbExp=7; IntAct=EBI-716327, EBI-373144; CC O75665; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-716327, EBI-744782; CC O75665; O75665: OFD1; NbExp=3; IntAct=EBI-716327, EBI-716327; CC O75665; Q15154: PCM1; NbExp=8; IntAct=EBI-716327, EBI-741421; CC O75665; P53350: PLK1; NbExp=4; IntAct=EBI-716327, EBI-476768; CC O75665; Q9Y265: RUVBL1; NbExp=3; IntAct=EBI-716327, EBI-353675; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome, centriole {ECO:0000269|PubMed:12595504, CC ECO:0000269|PubMed:14654843, ECO:0000269|PubMed:20230748, CC ECO:0000269|PubMed:26643951}. Cytoplasm, cytoskeleton, cilium basal CC body {ECO:0000269|PubMed:17761535}. Nucleus CC {ECO:0000269|PubMed:17761535}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriolar satellite CC {ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:26643951}. CC Note=Localizes to centriole distal ends and to centriolar satellites CC (PubMed:20230748, PubMed:24121310). Localization to centrioles and CC pericentriolar satellites may be mediated by KIAA0753/OFIP CC (PubMed:26643951). {ECO:0000269|PubMed:26643951}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=ODF1a; CC IsoId=O75665-1; Sequence=Displayed; CC Name=2; Synonyms=ODF1b; CC IsoId=O75665-2; Sequence=VSP_004177, VSP_004178; CC Name=3; CC IsoId=O75665-3; Sequence=VSP_023334; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in 9 and 14 weeks old CC embryos in metanephric mesenchyme, oral mucosa, lung, heart, nasal and CC cranial cartilage, and brain. Expressed in metanephros, brain, tongue, CC and limb. {ECO:0000269|PubMed:12595504}. CC -!- PTM: Phosphorylated. Phosphorylation at Ser-735, by the cAMP-dependent CC protein kinase PKA, triggers ubiquitination and proteasomal degradation CC of OFD1. Also increases its interaction with TBC1D31 and regulates its CC function in ciliogenesis. {ECO:0000269|PubMed:33934390}. CC -!- PTM: Ubiquitinated by PJA2, upon phosphorylation at Ser-735 by PKA, CC leads to the proteasomal degradation of OFD1. CC {ECO:0000269|PubMed:33934390}. CC -!- DISEASE: Orofaciodigital syndrome 1 (OFD1) [MIM:311200]: A form of CC orofaciodigital syndrome, a group of heterogeneous disorders CC characterized by abnormalities in the oral cavity, face, and digits and CC associated phenotypic abnormalities that lead to the delineation of CC various subtypes. OFD1 is X-linked dominant syndrome, lethal in males. CC Craniofacial findings consist of facial asymmetry, hypertelorism, CC median cleft, or pseudocleft of the upper lip, hypoplasia of the alae CC nasi, oral clefts and abnormal frenulea, tongue anomalies (clefting, CC cysts, hamartoma), and anomalous dentition involving missing or extra CC teeth. Asymmetric brachydactyly and/or syndactyly of the fingers and CC toes occur frequently. Approximately 50% of OFD1 females have some CC degree of intellectual disability. Some patients have structural CC central nervous system anomalies such as agenesis of the corpus CC callosum, cerebellar agenesis, or a Dandy-Walker malformation. Patients CC with OFD1 can develop fibrocystic disease of the liver and pancreas, in CC addition to polycystic kidneys. {ECO:0000269|PubMed:11179005, CC ECO:0000269|PubMed:11950863, ECO:0000269|PubMed:12595504, CC ECO:0000269|PubMed:16397067, ECO:0000269|PubMed:23033313}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Simpson-Golabi-Behmel syndrome 2 (SGBS2) [MIM:300209]: A CC severe variant of Simpson-Golabi-Behmel syndrome, a condition CC characterized by pre- and postnatal overgrowth (gigantism), facial CC dysmorphism and a variety of inconstant visceral and skeletal CC malformations. {ECO:0000269|PubMed:16783569}. Note=The disease may be CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Joubert syndrome 10 (JBTS10) [MIM:300804]: A disorder CC presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, CC neonatal breathing abnormalities and psychomotor delay. CC Neuroradiologically, it is characterized by cerebellar vermian CC hypoplasia/aplasia, thickened and reoriented superior cerebellar CC peduncles, and an abnormally large interpeduncular fossa, giving the CC appearance of a molar tooth on transaxial slices (molar tooth sign). CC Additional variable features include retinal dystrophy and renal CC disease. {ECO:0000269|PubMed:19800048, ECO:0000269|PubMed:26477546}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Retinitis pigmentosa 23 (RP23) [MIM:300424]: A retinal CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis CC pigmentosa is characterized by retinal pigment deposits visible on CC fundus examination and primary loss of rod photoreceptor cells followed CC by secondary loss of cone photoreceptors. Patients typically have night CC vision blindness and loss of midperipheral visual field. As their CC condition progresses, they lose their far peripheral visual field and CC eventually central vision as well. {ECO:0000269|PubMed:22619378}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the OFD1 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Oral-facial-digital syndrome 1 (OFD1); Note=Leiden CC Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/OFD1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y15164; CAA75436.1; -; mRNA. DR EMBL; Y16355; CAA76185.1; -; mRNA. DR EMBL; AC003037; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC096344; AAH96344.1; -; mRNA. DR CCDS; CCDS14157.1; -. [O75665-1] DR CCDS; CCDS83454.1; -. [O75665-3] DR RefSeq; NP_001317138.1; NM_001330209.1. [O75665-3] DR RefSeq; NP_003602.1; NM_003611.2. [O75665-1] DR AlphaFoldDB; O75665; -. DR SMR; O75665; -. DR BioGRID; 114055; 372. DR CORUM; O75665; -. DR DIP; DIP-60601N; -. DR IntAct; O75665; 287. DR MINT; O75665; -. DR STRING; 9606.ENSP00000344314; -. DR GlyGen; O75665; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75665; -. DR PhosphoSitePlus; O75665; -. DR SwissPalm; O75665; -. DR BioMuta; OFD1; -. DR EPD; O75665; -. DR jPOST; O75665; -. DR MassIVE; O75665; -. DR MaxQB; O75665; -. DR PaxDb; 9606-ENSP00000344314; -. DR PeptideAtlas; O75665; -. DR ProteomicsDB; 50145; -. [O75665-1] DR ProteomicsDB; 50146; -. [O75665-2] DR ProteomicsDB; 50147; -. [O75665-3] DR Pumba; O75665; -. DR Antibodypedia; 23854; 103 antibodies from 25 providers. DR DNASU; 8481; -. DR Ensembl; ENST00000340096.11; ENSP00000344314.6; ENSG00000046651.16. [O75665-1] DR Ensembl; ENST00000380550.6; ENSP00000369923.3; ENSG00000046651.16. [O75665-3] DR Ensembl; ENST00000682237.1; ENSP00000507121.1; ENSG00000046651.16. [O75665-2] DR GeneID; 8481; -. DR KEGG; hsa:8481; -. DR MANE-Select; ENST00000340096.11; ENSP00000344314.6; NM_003611.3; NP_003602.1. DR UCSC; uc004cvp.5; human. [O75665-1] DR AGR; HGNC:2567; -. DR CTD; 8481; -. DR DisGeNET; 8481; -. DR GeneCards; OFD1; -. DR GeneReviews; OFD1; -. DR HGNC; HGNC:2567; OFD1. DR HPA; ENSG00000046651; Low tissue specificity. DR MalaCards; OFD1; -. DR MIM; 300170; gene. DR MIM; 300209; phenotype. DR MIM; 300424; phenotype. DR MIM; 300804; phenotype. DR MIM; 311200; phenotype. DR neXtProt; NX_O75665; -. DR OpenTargets; ENSG00000046651; -. DR Orphanet; 475; Joubert syndrome. DR Orphanet; 2750; Orofaciodigital syndrome type 1. DR Orphanet; 2754; Orofaciodigital syndrome type 6. DR Orphanet; 244; Primary ciliary dyskinesia. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA31909; -. DR VEuPathDB; HostDB:ENSG00000046651; -. DR eggNOG; ENOG502QQR5; Eukaryota. DR GeneTree; ENSGT00390000001798; -. DR HOGENOM; CLU_011871_0_0_1; -. DR InParanoid; O75665; -. DR OMA; ERTYEMR; -. DR OrthoDB; 5398410at2759; -. DR PhylomeDB; O75665; -. DR TreeFam; TF331230; -. DR PathwayCommons; O75665; -. DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes. DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes. DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome. DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes. DR Reactome; R-HSA-5610787; Hedgehog 'off' state. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR Reactome; R-HSA-8854518; AURKA Activation by TPX2. DR SignaLink; O75665; -. DR SIGNOR; O75665; -. DR BioGRID-ORCS; 8481; 17 hits in 785 CRISPR screens. DR ChiTaRS; OFD1; human. DR GeneWiki; OFD1; -. DR GenomeRNAi; 8481; -. DR Pharos; O75665; Tbio. DR PRO; PR:O75665; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O75665; Protein. DR Bgee; ENSG00000046651; Expressed in sperm and 200 other cell types or tissues. DR ExpressionAtlas; O75665; baseline and differential. DR GO; GO:0034451; C:centriolar satellite; ISS:UniProtKB. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; IEA:GOC. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0031514; C:motile cilium; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0043014; F:alpha-tubulin binding; ISS:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060090; F:molecular adaptor activity; IMP:UniProt. DR GO; GO:0060271; P:cilium assembly; IMP:UniProt. DR GO; GO:0060287; P:epithelial cilium movement involved in determination of left/right asymmetry; ISS:UniProtKB. DR InterPro; IPR006594; LisH. DR PANTHER; PTHR39063:SF1; LISH DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR39063; ORAL-FACIAL-DIGITAL SYNDROME 1 PROTEIN HOMOLOG; 1. DR Pfam; PF16045; LisH_2; 1. DR SMART; SM00667; LisH; 1. DR PROSITE; PS50896; LISH; 1. DR Genevisible; O75665; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell projection; Ciliopathy; Cilium; KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Disease variant; Joubert syndrome; Nucleus; KW Phosphoprotein; Reference proteome; Retinitis pigmentosa; Ubl conjugation. FT CHAIN 1..1012 FT /note="Centriole and centriolar satellite protein OFD1" FT /id="PRO_0000058029" FT DOMAIN 70..102 FT /note="LisH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126" FT REGION 609..665 FT /note="Mediates homooligomerization" FT REGION 615..1012 FT /note="Mediates the interaction with SDCCAG8" FT /evidence="ECO:0000269|PubMed:20835237" FT REGION 719..744 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 757..794 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 824..904 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 963..1012 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 189..557 FT /evidence="ECO:0000255" FT COILED 622..662 FT /evidence="ECO:0000255" FT COILED 867..956 FT /evidence="ECO:0000255" FT COMPBIAS 723..742 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 870..904 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 965..979 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 983..999 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 663 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 669 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 720 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 735 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:33934390" FT MOD_RES 745 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 774 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 789 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 811 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 313..352 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023334" FT VAR_SEQ 352..367 FT /note="KYQLELKDDYIIRTNR -> NFHRLHGVCLALGILI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9722947" FT /id="VSP_004177" FT VAR_SEQ 368..1012 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9722947" FT /id="VSP_004178" FT VARIANT 74 FT /note="S -> F (in OFD1; dbSNP:rs312262812)" FT /evidence="ECO:0000269|PubMed:12595504" FT /id="VAR_015574" FT VARIANT 79 FT /note="A -> T (in OFD1; dbSNP:rs312262814)" FT /evidence="ECO:0000269|PubMed:11950863" FT /id="VAR_030789" FT VARIANT 138 FT /note="G -> S (in OFD1; dbSNP:rs312262827)" FT /evidence="ECO:0000269|PubMed:16397067" FT /id="VAR_058758" FT VARIANT 141 FT /note="M -> R (in OFD1; dbSNP:rs886039860)" FT /evidence="ECO:0000269|PubMed:23033313" FT /id="VAR_069100" FT VARIANT 307 FT /note="V -> D (in JBTS10; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26477546" FT /id="VAR_075701" FT VARIANT 358..360 FT /note="KDD -> FSY (in OFD1)" FT /evidence="ECO:0000269|PubMed:11179005" FT /id="VAR_013753" FT VARIANT 435 FT /note="S -> R (in OFD1; dbSNP:rs122460150)" FT /evidence="ECO:0000269|PubMed:11179005" FT /id="VAR_013754" FT MUTAGEN 97 FT /note="E->G: Increased protein stability." FT /evidence="ECO:0000269|PubMed:33934390" FT MUTAGEN 735 FT /note="S->A: Loss of phosphorylation by PKA. Loss of FT cAMP-dependent interaction with TBC1D31. Loss of FT ubiquitin-mediated proteasomal degradation. Loss of FT function in cilium assembly. Dominant negative effect." FT /evidence="ECO:0000269|PubMed:33934390" SQ SEQUENCE 1012 AA; 116671 MW; C2BF4376F89E6738 CRC64; MMAQSNMFTV ADVLSQDELR KKLYQTFKDR GILDTLKTQL RNQLIHELMH PVLSGELQPR SISVEGSSLL IGASNSLVAD HLQRCGYEYS LSVFFPESGL AKEKVFTMQD LLQLIKINPT SSLYKSLVSG SDKENQKGFL MHFLKELAEY HQAKESCNME TQTSSTFNRD SLAEKLQLID DQFADAYPQR IKFESLEIKL NEYKREIEEQ LRAEMCQKLK FFKDTEIAKI KMEAKKKYEK ELTMFQNDFE KACQAKSEAL VLREKSTLER IHKHQEIETK EIYAQRQLLL KDMDLLRGRE AELKQRVEAF ELNQKLQEEK HKSITEALRR QEQNIKSFEE TYDRKLKNEL LKYQLELKDD YIIRTNRLIE DERKNKEKAV HLQEELIAIN SKKEELNQSV NRVKELELEL ESVKAQSLAI TKQNHMLNEK VKEMSDYSLL KEEKLELLAQ NKLLKQQLEE SRNENLRLLN RLAQPAPELA VFQKELRKAE KAIVVEHEEF ESCRQALHKQ LQDEIEHSAQ LKAQILGYKA SVKSLTTQVA DLKLQLKQTQ TALENEVYCN PKQSVIDRSV NGLINGNVVP CNGEISGDFL NNPFKQENVL ARMVASRITN YPTAWVEGSS PDSDLEFVAN TKARVKELQQ EAERLEKAFR SYHRRVIKNS AKSPLAAKSP PSLHLLEAFK NITSSSPERH IFGEDRVVSE QPQVGTLEER NDVVEALTGS AASRLRGGTS SRRLSSTPLP KAKRSLESEM YLEGLGRSHI ASPSPCPDRM PLPSPTESRH SLSIPPVSSP PEQKVGLYRR QTELQDKSEF SDVDKLAFKD NEEFESSFES AGNMPRQLEM GGLSPAGDMS HVDAAAAAVP LSYQHPSVDQ KQIEEQKEEE KIREQQVKER RQREERRQSN LQEVLERERR ELEKLYQERK MIEESLKIKI KKELEMENEL EMSNQEIKDK SAHSENPLEK YMKIIQQEQD QESADKSSKK MVQEGSLVDT LQSSDKVESL TGFSHEELDD SW //