OFD1_HUMAN
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 03-AUG-2022, entry version 192.
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 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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
RP VARIANTS OFD1 358-PHE--TYR-360 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 [21]
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 [22]
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 [23]
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 [24]
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. Involved in the
CC biogenesis of the cilium, a centriole-associated function. The cilium
CC is a cell surface projection found in many vertebrate cells required to
CC transduce signals important for development and tissue homeostasis.
CC Plays an important role in development by regulating Wnt signaling and
CC the specification of the left-right axis. Only OFD1 localized at the
CC centriolar satellites is removed by autophagy, which is an important
CC step in the ciliogenesis regulation (By similarity). {ECO:0000250}.
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).
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 -!- 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 -!- 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";
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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; 364.
DR CORUM; O75665; -.
DR DIP; DIP-60601N; -.
DR IntAct; O75665; 284.
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; O75665; -.
DR PeptideAtlas; O75665; -.
DR PRIDE; O75665; -.
DR ProteomicsDB; 50145; -. [O75665-1]
DR ProteomicsDB; 50146; -. [O75665-2]
DR ProteomicsDB; 50147; -. [O75665-3]
DR Antibodypedia; 23854; 94 antibodies from 24 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 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; 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; EVMRTRE; -.
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; 13 hits in 708 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 198 other tissues.
DR ExpressionAtlas; O75665; baseline and differential.
DR Genevisible; O75665; HS.
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:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0060287; P:epithelial cilium movement involved in determination of left/right asymmetry; ISS:UniProtKB.
DR InterPro; IPR006594; LisH.
DR Pfam; PF16045; LisH_2; 1.
DR SMART; SM00667; LisH; 1.
DR PROSITE; PS50896; LISH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium;
KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Joubert syndrome; Nucleus; Phosphoprotein;
KW Reference proteome; Retinitis pigmentosa.
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 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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26477546"
FT /id="VAR_075701"
FT VARIANT 358..360
FT /note="KDD -> FSY (in OFD1)"
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"
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
