ID OPA1_HUMAN Reviewed; 960 AA. AC O60313; D3DNW4; E5KLJ5; E5KLJ6; E5KLJ7; E5KLK1; E5KLK2; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 27-MAR-2024, entry version 214. DE RecName: Full=Dynamin-like 120 kDa protein, mitochondrial; DE EC=3.6.5.5 {ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:28746876}; DE AltName: Full=Optic atrophy protein 1; DE Contains: DE RecName: Full=Dynamin-like 120 kDa protein, form S1; DE Flags: Precursor; GN Name=OPA1 {ECO:0000303|PubMed:11810270, ECO:0000303|PubMed:28746876, GN ECO:0000312|HGNC:HGNC:8140}; Synonyms=KIAA0567; 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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-158. RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 3; 4; 5 AND 7). RX PubMed=20843780; DOI=10.1093/nar/gkq750; RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., RA Speed T.P., Scharfe C.; RT "Identification of rare DNA variants in mitochondrial disorders with RT improved array-based sequencing."; RL Nucleic Acids Res. 39:44-58(2011). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-158. RC TISSUE=Brain; 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 [6] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), ALTERNATIVE RP SPLICING, TISSUE SPECIFICITY, AND VARIANTS OPA1 GLN-290; ARG-785 AND RP PRO-939. RX PubMed=11810270; DOI=10.1007/s00439-001-0633-y; RA Delettre C., Griffoin J.-M., Kaplan J., Dollfus H., Lorenz B., Faivre L., RA Lenaers G., Belenguer P., Hamel C.P.; RT "Mutation spectrum and splicing variants in the OPA1 gene."; RL Hum. Genet. 109:584-591(2001). RN [7] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT OPA1 GLU-300. RX PubMed=11017079; DOI=10.1038/79936; RA Delettre C., Lenaers G., Griffoin J.-M., Gigarel N., Lorenzo C., RA Belenguer P., Pelloquin L., Grosgeorge J., Turc-Carel C., Perret E., RA Astarie-Dequeker C., Lasquellec L., Arnaud B., Ducommun B., Kaplan J., RA Hamel C.P.; RT "Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is RT mutated in dominant optic atrophy."; RL Nat. Genet. 26:207-210(2000). RN [8] RP TISSUE SPECIFICITY, AND VARIANTS OPA1 GLN-290 AND ILE-432 DEL. RX PubMed=11017080; DOI=10.1038/79944; RA Alexander C., Votruba M., Pesch U.E.A., Thiselton D.L., Mayer S., Moore A., RA Rodriguez M., Kellner U., Leo-Kottler B., Auburger G., Bhattacharya S.S., RA Wissinger B.; RT "OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant RT optic atrophy linked to chromosome 3q28."; RL Nat. Genet. 26:211-215(2000). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING. RX PubMed=16778770; DOI=10.1038/sj.emboj.7601184; RA Ishihara N., Fujita Y., Oka T., Mihara K.; RT "Regulation of mitochondrial morphology through proteolytic cleavage of RT OPA1."; RL EMBO J. 25:2966-2977(2006). RN [10] RP FUNCTION, ALTERNATIVE SPLICING, AND PROTEOLYTIC CLEAVAGE. RX PubMed=17709429; DOI=10.1083/jcb.200704110; RA Song Z., Chen H., Fiket M., Alexander C., Chan D.C.; RT "OPA1 processing controls mitochondrial fusion and is regulated by mRNA RT splicing, membrane potential, and Yme1L."; RL J. Cell Biol. 178:749-755(2007). RN [11] RP FUNCTION (DYNAMIN-LIKE 120 KDA PROTEIN; FORM S1), AND PROTEOLYTIC RP PROCESSING. RX PubMed=20038677; DOI=10.1083/jcb.200906083; RA Head B., Griparic L., Amiri M., Gandre-Babbe S., van der Bliek A.M.; RT "Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease RT in mammalian cells."; RL J. Cell Biol. 187:959-966(2009). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-228, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [13] RP INTERACTION WITH PRELID1. RX PubMed=21364629; DOI=10.1038/cddis.2009.19; RA McKeller M.R., Herrera-Rodriguez S., Ma W., Ortiz-Quintero B., Rangel R., RA Cande C., Sims-Mourtada J.C., Melnikova V., Kashi C., Phan L.M., Chen Z., RA Huang P., Dunner K. Jr., Kroemer G., Singh K.K., Martinez-Valdez H.; RT "Vital function of PRELI and essential requirement of its LEA motif."; RL Cell Death Dis. 1:E21-E21(2010). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, CHARACTERIZATION OF VARIANTS OPA1 RP GLU-300; VAL-439; HIS-445; ARG-545; LYS-728; ARG-785 AND PRO-939, AND RP CHARACTERIZATION OF VARIANTS VARIANT DOA+ THR-357; VAL-439; HIS-445; RP ARG-545 AND ASP-910. RX PubMed=20185555; DOI=10.1093/hmg/ddq088; RA Ban T., Heymann J.A., Song Z., Hinshaw J.E., Chan D.C.; RT "OPA1 disease alleles causing dominant optic atrophy have defects in RT cardiolipin-stimulated GTP hydrolysis and membrane tubulation."; RL Hum. Mol. Genet. 19:2113-2122(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP INVOLVEMENT IN DOA+, AND VARIANT DOA+ TYR-551. RX PubMed=21112924; DOI=10.1093/brain/awq306; RA Marelli C., Amati-Bonneau P., Reynier P., Layet V., Layet A., Stevanin G., RA Brissaud E., Bonneau D., Durr A., Brice A.; RT "Heterozygous OPA1 mutations in Behr syndrome."; RL Brain 134:E169-E169(2011). RN [17] RP FUNCTION (ISOFORMS 4 AND 5), AND SUBCELLULAR LOCATION. RX PubMed=20974897; DOI=10.1101/gr.108696.110; RA Elachouri G., Vidoni S., Zanna C., Pattyn A., Boukhaddaoui H., Gaget K., RA Yu-Wai-Man P., Gasparre G., Sarzi E., Delettre C., Olichon A., Loiseau D., RA Reynier P., Chinnery P.F., Rotig A., Carelli V., Hamel C.P., Rugolo M., RA Lenaers G.; RT "OPA1 links human mitochondrial genome maintenance to mtDNA replication and RT distribution."; RL Genome Res. 21:12-20(2011). RN [18] RP INTERACTION WITH CHCHD3 AND IMMT. RX PubMed=21081504; DOI=10.1074/jbc.m110.171975; RA Darshi M., Mendiola V.L., Mackey M.R., Murphy A.N., Koller A., RA Perkins G.A., Ellisman M.H., Taylor S.S.; RT "ChChd3, an inner mitochondrial membrane protein, is essential for RT maintaining crista integrity and mitochondrial function."; RL J. Biol. Chem. 286:2918-2932(2011). RN [19] RP INVOLVEMENT IN BEHRS, AND VARIANT BEHRS MET-382. RX PubMed=21636302; DOI=10.1016/j.ymgme.2011.04.018; RA Schaaf C.P., Blazo M., Lewis R.A., Tonini R.E., Takei H., Wang J., RA Wong L.J., Scaglia F.; RT "Early-onset severe neuromuscular phenotype associated with compound RT heterozygosity for OPA1 mutations."; RL Mol. Genet. Metab. 103:383-387(2011). RN [20] RP INVOLVEMENT IN BEHRS, AND VARIANTS BEHRS MET-382; MET-402 AND LYS-487. RX PubMed=25012220; DOI=10.1093/brain/awu184; RA Bonneau D., Colin E., Oca F., Ferre M., Chevrollier A., Gueguen N., RA Desquiret-Dumas V., N'Guyen S., Barth M., Zanlonghi X., Rio M., RA Desguerre I., Barnerias C., Momtchilova M., Rodriguez D., Slama A., RA Lenaers G., Procaccio V., Amati-Bonneau P., Reynier P.; RT "Early-onset Behr syndrome due to compound heterozygous mutations in RT OPA1."; RL Brain 137:E301-E301(2014). RN [21] RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION. RX PubMed=24616225; DOI=10.1083/jcb.201308006; RA Anand R., Wai T., Baker M.J., Kladt N., Schauss A.C., Rugarli E., RA Langer T.; RT "The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial RT fusion and fission."; RL J. Cell Biol. 204:919-929(2014). RN [22] 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 [23] RP INVOLVEMENT IN BEHRS, AND VARIANT BEHRS MET-382. RX PubMed=25146916; DOI=10.1093/brain/awu234; RA Carelli V., Sabatelli M., Carrozzo R., Rizza T., Schimpf S., Wissinger B., RA Zanna C., Rugolo M., La Morgia C., Caporali L., Carbonelli M., Barboni P., RA Tonon C., Lodi R., Bertini E.; RT "'Behr syndrome' with OPA1 compound heterozygote mutations."; RL Brain 138:E321-E321(2015). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [25] RP PROTEOLYTIC CLEAVAGE BY YME1L. RX PubMed=27495975; DOI=10.7554/elife.16078; RA Hartmann B., Wai T., Hu H., MacVicar T., Musante L., Fischer-Zirnsak B., RA Stenzel W., Graef R., van den Heuvel L., Ropers H.H., Wienker T.F., RA Huebner C., Langer T., Kaindl A.M.; RT "Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and RT mitochondrial network fragmentation."; RL Elife 5:0-0(2016). RN [26] RP INVOLVEMENT IN MTDPS14, AND VARIANT MTDPS14 ARG-534. RX PubMed=26561570; DOI=10.1136/jmedgenet-2015-103361; RA Spiegel R., Saada A., Flannery P.J., Burte F., Soiferman D., Khayat M., RA Eisner V., Vladovski E., Taylor R.W., Bindoff L.A., Shaag A., Mandel H., RA Schuler-Furman O., Shalev S.A., Elpeleg O., Yu-Wai-Man P.; RT "Fatal infantile mitochondrial encephalomyopathy, hypertrophic RT cardiomyopathy and optic atrophy associated with a homozygous OPA1 RT mutation."; RL J. Med. Genet. 53:127-131(2016). RN [27] RP ACTIVITY REGULATION, SUBUNIT, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=28746876; DOI=10.1016/j.celrep.2017.06.090; RA Huang G., Massoudi D., Muir A.M., Joshi D.C., Zhang C.L., Chiu S.Y., RA Greenspan D.S.; RT "WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for RT Mitochondrial Fusion."; RL Cell Rep. 20:923-934(2017). RN [28] RP VARIANTS OPA1 LYS-270; ALA-273; GLN-290; TRP-290; VAL-438; GLU-468; CYS-551 RP DEL AND ARG-785, AND VARIANTS ASN-158; VAL-192 AND ASN-550. RX PubMed=11440988; DOI=10.1093/hmg/10.13.1359; RA Pesch U.E.A., Leo-Kottler B., Mayer S., Jurklies B., Kellner U., RA Apfelstedt-Sylla E., Zrenner E., Alexander C., Wissinger B.; RT "OPA1 mutations in patients with autosomal dominant optic atrophy and RT evidence for semi-dominant inheritance."; RL Hum. Mol. Genet. 10:1359-1368(2001). RN [29] RP VARIANTS OPA1 GLN-290; GLU-300; PHE-384; LYS-503 AND ASN-505, AND VARIANTS RP ASN-158 AND GLY-907. RX PubMed=11440989; DOI=10.1093/hmg/10.13.1369; RA Toomes C., Marchbank N.J., Mackey D.A., Craig J.E., Newbury-Ecob R.A., RA Bennett C.P., Vize C.J., Desai S.P., Black G.C.M., Patel N., Teimory M., RA Markham A.F., Inglehearn C.F., Churchill A.J.; RT "Spectrum, frequency and penetrance of OPA1 mutations in dominant optic RT atrophy."; RL Hum. Mol. Genet. 10:1369-1378(2001). RN [30] RP VARIANTS OPA1 38-ARG--SER-43 DEL; 586-ARG--ASP-589 DEL; ARG-396; ILE-432 RP DEL; LYS-503 AND HIS-571, AND VARIANTS ASN-158; LEU-167 AND VAL-192. RX PubMed=12036970; RA Thiselton D.L., Alexander C., Taanman J.-W., Brooks S., Rosenberg T., RA Eiberg H., Andreasson S., Van Regemorter N., Munier F.L., Moore A.T., RA Bhattacharya S.S., Votruba M.; RT "A comprehensive survey of mutations in the OPA1 gene in patients with RT autosomal dominant optic atrophy."; RL Invest. Ophthalmol. Vis. Sci. 43:1715-1724(2002). RN [31] RP VARIANT OPA1 HIS-445. RX PubMed=12566046; DOI=10.1016/s0002-9394(02)01929-3; RA Shimizu S., Mori N., Kishi M., Sugata H., Tsuda A., Kubota N.; RT "A novel mutation in the OPA1 gene in a Japanese patient with optic RT atrophy."; RL Am. J. Ophthalmol. 135:256-257(2003). RN [32] RP VARIANTS OPA1 PRO-272; GLY-470; PRO-574 AND 700-LEU-LYS-701 DEL. RX PubMed=14961560; DOI=10.1002/humu.9152; RA Baris O., Delettre C., Amati-Bonneau P., Surget M.-O., Charlin J.-F., RA Catier A., Derieux L., Guyomard J.-L., Dollfus H., Jonveaux P., Ayuso C., RA Maumenee I., Lorenz B., Mohammed S., Tourmen Y., Bonneau D., Malthiery Y., RA Hamel C., Reynier P.; RT "Fourteen novel OPA1 mutations in autosomal dominant optic atrophy RT including two de novo mutations in sporadic optic atrophy."; RL Hum. Mutat. 21:656-656(2003). RN [33] RP VARIANT DOA+ HIS-445. RX PubMed=15531309; DOI=10.1016/j.ajo.2004.06.011; RA Payne M., Yang Z., Katz B.J., Warner J.E.A., Weight C.J., Zhao Y., RA Pearson E.D., Treft R.L., Hillman T., Kennedy R.J., Meire F.M., Zhang K.; RT "Dominant optic atrophy, sensorineural hearing loss, ptosis, and RT ophthalmoplegia: a syndrome caused by a missense mutation in OPA1."; RL Am. J. Ophthalmol. 138:749-755(2004). RN [34] RP VARIANTS OPA1 324-ARG--PRO-326 DEL; TRP-590 AND LYS-728, AND VARIANT RP ASN-158. RX PubMed=15948788; DOI=10.1111/j.1600-0420.2005.00448.x; RA Puomila A., Huoponen K., Maentyjaervi M., Haemaelaeinen P., Paananen R., RA Sankila E.-M., Savontaus M.-L., Somer M., Nikoskelainen E.; RT "Dominant optic atrophy: correlation between clinical and molecular genetic RT studies."; RL Acta Ophthalmol. Scand. 83:337-346(2005). RN [35] RP VARIANT DOA+ HIS-445. RX PubMed=16240368; DOI=10.1002/ana.20681; RA Amati-Bonneau P., Guichet A., Olichon A., Chevrollier A., Viala F., RA Miot S., Ayuso C., Odent S., Arrouet C., Verny C., Calmels M.-N., RA Simard G., Belenguer P., Wang J., Puel J.-L., Hamel C., Malthiery Y., RA Bonneau D., Lenaers G., Reynier P.; RT "OPA1 R445H mutation in optic atrophy associated with sensorineural RT deafness."; RL Ann. Neurol. 58:958-963(2005). RN [36] RP VARIANTS OPA1 SER-8; CYS-80 AND CYS-841, AND VARIANTS ASN-158 AND VAL-192. RX PubMed=16617242; DOI=10.1097/01.gim.0000214299.61930.c0; RA Han J., Thompson-Lowrey A.J., Reiss A., Mayorov V., Jia H., Biousse V., RA Newman N.J., Brown M.D.; RT "OPA1 mutations and mitochondrial DNA haplotypes in autosomal dominant RT optic atrophy."; RL Genet. Med. 8:217-225(2006). RN [37] RP VARIANT OPA1 ARG-545. RX PubMed=16513463; DOI=10.1016/j.ophtha.2005.10.054; RA Nakamura M., Lin J., Ueno S., Asaoka R., Hirai T., Hotta Y., Miyake Y., RA Terasaki H.; RT "Novel mutations in the OPA1 gene and associated clinical features in RT Japanese patients with optic atrophy."; RL Ophthalmology 113:483-488(2006). RN [38] RP VARIANT OPA1 HIS-229 (ISOFORM 2). RX PubMed=18360822; DOI=10.1002/ana.21376; RA Cornille K., Milea D., Amati-Bonneau P., Procaccio V., Zazoun L., RA Guillet V., El Achouri G., Delettre C., Gueguen N., Loiseau D., Muller A., RA Ferre M., Chevrollier A., Wallace D.C., Bonneau D., Hamel C., Reynier P., RA Lenaers G.; RT "Reversible optic neuropathy with OPA1 exon 5b mutation."; RL Ann. Neurol. 63:667-671(2008). RN [39] RP VARIANT DOA+ CYS-582. RX PubMed=18195150; DOI=10.1001/archneurol.2007.9; RA Ferraris S., Clark S., Garelli E., Davidzon G., Moore S.A., Kardon R.H., RA Bienstock R.J., Longley M.J., Mancuso M., Gutierrez Rios P., Hirano M., RA Copeland W.C., DiMauro S.; RT "Progressive external ophthalmoplegia and vision and hearing loss in a RT patient with mutations in POLG2 and OPA1."; RL Arch. Neurol. 65:125-131(2008). RN [40] RP VARIANT DOA+ ARG-545. RX PubMed=18065439; DOI=10.1093/brain/awm272; RA Hudson G., Amati-Bonneau P., Blakely E.L., Stewart J.D., He L., RA Schaefer A.M., Griffiths P.G., Ahlqvist K., Suomalainen A., Reynier P., RA McFarland R., Turnbull D.M., Chinnery P.F., Taylor R.W.; RT "Mutation of OPA1 causes dominant optic atrophy with external RT ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: RT a novel disorder of mtDNA maintenance."; RL Brain 131:329-337(2008). RN [41] RP VARIANTS DOA+ THR-357; VAL-439; HIS-445; ARG-545 AND ASP-910, AND FUNCTION. RX PubMed=18158317; DOI=10.1093/brain/awm298; RA Amati-Bonneau P., Valentino M.L., Reynier P., Gallardo M.E., Bornstein B., RA Boissiere A., Campos Y., Rivera H., de la Aleja J.G., Carroccia R., RA Iommarini L., Labauge P., Figarella-Branger D., Marcorelles P., Furby A., RA Beauvais K., Letournel F., Liguori R., La Morgia C., Montagna P., RA Liguori M., Zanna C., Rugolo M., Cossarizza A., Wissinger B., Verny C., RA Schwarzenbacher R., Martin M.A., Arenas J., Ayuso C., Garesse R., RA Lenaers G., Bonneau D., Carelli V.; RT "OPA1 mutations induce mitochondrial DNA instability and optic atrophy RT 'plus' phenotypes."; RL Brain 131:338-351(2008). RN [42] RP VARIANT OPA1 VAL-439. RX PubMed=18204809; DOI=10.1007/s00415-008-0571-x; RA Liguori M., La Russa A., Manna I., Andreoli V., Caracciolo M., RA Spadafora P., Cittadella R., Quattrone A.; RT "A phenotypic variation of dominant optic atrophy and deafness (ADOAD) due RT to a novel OPA1 mutation."; RL J. Neurol. 255:127-129(2008). RN [43] RP VARIANTS OPA1 MET-95; CYS-102; 293-VAL-VAL-294 DEL; ARG-310; THR-357; RP MET-382; PRO-396; 429-PRO-ASN-430 DEL; ASP-430; ARG-449; PHE-ILE-PHE-463 RP INS; LYS-487; ARG-545; TYR-551; GLN-590; PRO-593; LEU-646; ASP-768; RP TRP-781; TYR-823; LEU-882; PRO-887; CYS-932 AND PRO-949. RX PubMed=19319978; DOI=10.1002/humu.21025; RA Ferre M., Bonneau D., Milea D., Chevrollier A., Verny C., Dollfus H., RA Ayuso C., Defoort S., Vignal C., Zanlonghi X., Charlin J.-F., Kaplan J., RA Odent S., Hamel C.P., Procaccio V., Reynier P., Amati-Bonneau P.; RT "Molecular screening of 980 cases of suspected hereditary optic neuropathy RT with a report on 77 novel OPA1 mutations."; RL Hum. Mutat. 30:E692-E705(2009). RN [44] RP VARIANT OPA1 CYS-932. RX PubMed=19325939; RA Nochez Y., Arsene S., Gueguen N., Chevrollier A., Ferre M., Guillet V., RA Desquiret V., Toutain A., Bonneau D., Procaccio V., Amati-Bonneau P., RA Pisella P.-J., Reynier P.; RT "Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to RT a mitochondrial coupling defect."; RL Mol. Vis. 15:598-608(2009). RN [45] RP VARIANTS OPA1 LEU-593 DEL AND PRO-949, AND VARIANT GLY-502. RX PubMed=19969356; DOI=10.1016/j.ophtha.2009.07.019; RA Yen M.Y., Wang A.G., Lin Y.C., Fann M.J., Hsiao K.J.; RT "Novel mutations of the OPA1 gene in Chinese dominant optic atrophy."; RL Ophthalmology 117:392-396(2010). RN [46] RP VARIANT OPA1 ALA-400. RX PubMed=22382025; DOI=10.1016/j.bbrc.2012.02.073; RA Zhang J., Yuan Y., Lin B., Feng H., Li Y., Dai X., Zhou H., Dong X., RA Liu X.L., Guan M.X.; RT "A novel OPA1 mutation in a Chinese family with autosomal dominant optic RT atrophy."; RL Biochem. Biophys. Res. Commun. 419:670-675(2012). RN [47] RP VARIANTS OPA1 GLU-459 AND VAL-910 DEL. RX PubMed=22857269; DOI=10.1186/1471-2350-13-65; RA Almind G.J., Ek J., Rosenberg T., Eiberg H., Larsen M., Lucamp L., RA Brondum-Nielsen K., Gronskov K.; RT "Dominant optic atrophy in Denmark - report of 15 novel mutations in OPA1, RT using a strategy with a detection rate of 90%."; RL BMC Med. Genet. 13:65-65(2012). RN [48] RP VARIANT DOA+ PRO-449. RX PubMed=23387428; DOI=10.1111/aos.12038; RA Liskova P., Ulmanova O., Tesina P., Melsova H., Diblik P., Hansikova H., RA Tesarova M., Votruba M.; RT "Novel OPA1 missense mutation in a family with optic atrophy and severe RT widespread neurological disorder."; RL Acta Ophthalmol. 91:E225-E231(2013). RN [49] RP VARIANTS OPA1 SER-330 AND ILE-377. RX PubMed=23401657; RA Chen Y., Jia X., Wang P., Xiao X., Li S., Guo X., Zhang Q.; RT "Mutation survey of the optic atrophy 1 gene in 193 Chinese families with RT suspected hereditary optic neuropathy."; RL Mol. Vis. 19:292-302(2013). CC -!- FUNCTION: Dynamin-related GTPase that is essential for normal CC mitochondrial morphology by regulating the equilibrium between CC mitochondrial fusion and mitochondrial fission (PubMed:16778770, CC PubMed:17709429, PubMed:20185555, PubMed:24616225, PubMed:28746876). CC Coexpression of isoform 1 with shorter alternative products is required CC for optimal activity in promoting mitochondrial fusion CC (PubMed:17709429). Binds lipid membranes enriched in negatively charged CC phospholipids, such as cardiolipin, and promotes membrane tubulation CC (PubMed:20185555). The intrinsic GTPase activity is low, and is CC strongly increased by interaction with lipid membranes CC (PubMed:20185555). Plays a role in remodeling cristae and the release CC of cytochrome c during apoptosis (By similarity). Proteolytic CC processing in response to intrinsic apoptotic signals may lead to CC disassembly of OPA1 oligomers and release of the caspase activator CC cytochrome C (CYCS) into the mitochondrial intermembrane space (By CC similarity). Plays a role in mitochondrial genome maintenance CC (PubMed:20974897, PubMed:18158317). {ECO:0000250|UniProtKB:P58281, CC ECO:0000269|PubMed:16778770, ECO:0000269|PubMed:17709429, CC ECO:0000269|PubMed:18158317, ECO:0000269|PubMed:20185555, CC ECO:0000269|PubMed:20974897, ECO:0000269|PubMed:24616225, CC ECO:0000269|PubMed:28746876}. CC -!- FUNCTION: [Dynamin-like 120 kDa protein, form S1]: Inactive form CC produced by cleavage at S1 position by OMA1 following stress conditions CC that induce loss of mitochondrial membrane potential, leading to CC negative regulation of mitochondrial fusion. CC {ECO:0000269|PubMed:20038677}. CC -!- FUNCTION: [Isoform 4]: Isoforms that contain the alternative exon 4b CC are required for mitochondrial genome maintenance, possibly by CC anchoring the mitochondrial nucleoids to the inner mitochondrial CC membrane. {ECO:0000269|PubMed:20974897}. CC -!- FUNCTION: [Isoform 5]: Isoforms that contain the alternative exon 4b CC are required for mitochondrial genome maintenance, possibly by CC anchoring the mitochondrial nucleoids to the inner mitochondrial CC membrane. {ECO:0000269|PubMed:20974897}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.5; CC Evidence={ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:28746876}; CC -!- ACTIVITY REGULATION: Activated by guanine nucleotide exchange factor CC RCC1L. {ECO:0000269|PubMed:28746876}. CC -!- SUBUNIT: Oligomeric complex consisting of membrane-bound and soluble CC forms of OPA1. Interacts with RCC1L; this interaction is direct CC (PubMed:28746876). Interacts with CHCHD3 and IMMT; these interactions CC occur preferentially with soluble OPA1 forms (PubMed:21081504). Binds CC PARL (By similarity). Interacts with PRELID1 (PubMed:21364629). CC {ECO:0000250|UniProtKB:P58281, ECO:0000269|PubMed:20185555, CC ECO:0000269|PubMed:21081504, ECO:0000269|PubMed:21364629, CC ECO:0000269|PubMed:28746876}. CC -!- INTERACTION: CC O60313; Q12983: BNIP3; NbExp=10; IntAct=EBI-1054131, EBI-749464; CC O60313; Q5S007: LRRK2; NbExp=5; IntAct=EBI-1054131, EBI-5323863; CC O60313; Q9NTG7: SIRT3; NbExp=3; IntAct=EBI-1054131, EBI-724621; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:11017079, ECO:0000269|PubMed:16778770, CC ECO:0000269|PubMed:20974897, ECO:0000269|PubMed:28746876}; Single-pass CC membrane protein {ECO:0000255}. Mitochondrion intermembrane space CC {ECO:0000250|UniProtKB:P58281}. Mitochondrion membrane CC {ECO:0000269|PubMed:24616225}. Note=Detected at contact sites between CC endoplasmic reticulum and mitochondrion membranes. CC {ECO:0000269|PubMed:24616225}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Comment=Additional isoforms seem to exist. CC {ECO:0000305|PubMed:11810270, ECO:0000305|PubMed:17709429}; CC Name=1; Synonyms=6; CC IsoId=O60313-1; Sequence=Displayed; CC Name=2; Synonyms=7 {ECO:0000303|PubMed:16778770}; CC IsoId=O60313-2; Sequence=VSP_021035; CC Name=3; CC IsoId=O60313-9; Sequence=VSP_059072, VSP_059074; CC Name=4; CC IsoId=O60313-10; Sequence=VSP_059073, VSP_059074; CC Name=5; CC IsoId=O60313-11; Sequence=VSP_059073; CC Name=7; CC IsoId=O60313-13; Sequence=VSP_059072; CC -!- TISSUE SPECIFICITY: Highly expressed in retina. Also expressed in CC brain, testis, heart and skeletal muscle. Isoform 1 expressed in CC retina, skeletal muscle, heart, lung, ovary, colon, thyroid gland, CC leukocytes and fetal brain. Isoform 2 expressed in colon, liver, CC kidney, thyroid gland and leukocytes. Low levels of all isoforms CC expressed in a variety of tissues. {ECO:0000269|PubMed:11017079, CC ECO:0000269|PubMed:11017080, ECO:0000269|PubMed:11810270}. CC -!- PTM: PARL-dependent proteolytic processing releases an antiapoptotic CC soluble form not required for mitochondrial fusion. Cleaved by OMA1 at CC position S1 following stress conditions. {ECO:0000269|PubMed:20038677}. CC -!- PTM: [Isoform 2]: Cleavage at position S2 is mediated by YME1L CC (PubMed:17709429, PubMed:24616225, PubMed:27495975). Cleavage may occur CC in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) CC (PubMed:16778770). {ECO:0000269|PubMed:16778770, CC ECO:0000269|PubMed:17709429, ECO:0000269|PubMed:24616225, CC ECO:0000269|PubMed:27495975}. CC -!- PTM: [Isoform 3]: Cleavage at position S2 is mediated by YME1L CC (PubMed:17709429, PubMed:24616225, PubMed:27495975). Cleavage may occur CC in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) CC (PubMed:16778770). {ECO:0000269|PubMed:16778770, CC ECO:0000269|PubMed:17709429, ECO:0000269|PubMed:24616225, CC ECO:0000269|PubMed:27495975}. CC -!- PTM: [Isoform 4]: Cleavage at position S2 is mediated by YME1L CC (PubMed:17709429, PubMed:24616225, PubMed:27495975). Cleavage may occur CC in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) CC (PubMed:16778770). {ECO:0000269|PubMed:16778770, CC ECO:0000269|PubMed:17709429, ECO:0000269|PubMed:24616225, CC ECO:0000269|PubMed:27495975}. CC -!- DISEASE: Optic atrophy 1 (OPA1) [MIM:165500]: A condition that features CC progressive visual loss in association with optic atrophy. Atrophy of CC the optic disk indicates a deficiency in the number of nerve fibers CC which arise in the retina and converge to form the optic disk, optic CC nerve, optic chiasm and optic tracts. OPA1 is characterized by an CC insidious onset of visual impairment in early childhood with moderate CC to severe loss of visual acuity, temporal optic disk pallor, color CC vision deficits, and centrocecal scotoma of variable density. CC {ECO:0000269|PubMed:11017079, ECO:0000269|PubMed:11017080, CC ECO:0000269|PubMed:11440988, ECO:0000269|PubMed:11440989, CC ECO:0000269|PubMed:11810270, ECO:0000269|PubMed:12036970, CC ECO:0000269|PubMed:12566046, ECO:0000269|PubMed:14961560, CC ECO:0000269|PubMed:15948788, ECO:0000269|PubMed:16513463, CC ECO:0000269|PubMed:16617242, ECO:0000269|PubMed:18204809, CC ECO:0000269|PubMed:18360822, ECO:0000269|PubMed:19319978, CC ECO:0000269|PubMed:19325939, ECO:0000269|PubMed:19969356, CC ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:22382025, CC ECO:0000269|PubMed:22857269, ECO:0000269|PubMed:23401657}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Dominant optic atrophy plus syndrome (DOA+) [MIM:125250]: A CC neurologic disorder characterized most commonly by an insidious onset CC of visual loss and sensorineural hearing loss in childhood with CC variable presentation of other clinical manifestations including CC progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and CC ataxia. There appears to be a wide range of intermediate phenotypes. CC {ECO:0000269|PubMed:15531309, ECO:0000269|PubMed:16240368, CC ECO:0000269|PubMed:18065439, ECO:0000269|PubMed:18158317, CC ECO:0000269|PubMed:18195150, ECO:0000269|PubMed:20185555, CC ECO:0000269|PubMed:21112924, ECO:0000269|PubMed:23387428}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Behr syndrome (BEHRS) [MIM:210000]: An autosomal recessive CC syndrome characterized by optic atrophy beginning in early childhood CC associated with ataxia, pyramidal signs, spasticity, intellectual CC disability, and posterior column sensory loss. The ataxia, spasticity, CC and muscle contractures, mainly of the hip adductors, hamstrings, and CC soleus, are progressive and become more prominent in the second decade. CC {ECO:0000269|PubMed:21636302, ECO:0000269|PubMed:25012220, CC ECO:0000269|PubMed:25146916}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 14, CC cardioencephalomyopathic type (MTDPS14) [MIM:616896]: An autosomal CC recessive mitochondrial disorder characterized by lethal infantile CC encephalopathy, hypertrophic cardiomyopathy and optic atrophy. Skeletal CC muscle biopsies show significant mtDNA depletion and abnormal CC mitochondria. {ECO:0000269|PubMed:26561570}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 4]: Contains the alternative exon 4b that is CC important for mitochondrial genome maintenance. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Contains the alternative exon 4b that is CC important for mitochondrial genome maintenance. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase CC superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE- CC ProRule:PRU01055}. CC -!- SEQUENCE CAUTION: CC Sequence=AF416919; Type=Miscellaneous discrepancy; Evidence={ECO:0000305}; 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; AB011139; BAA25493.1; -; mRNA. DR EMBL; HQ204906; ADP90054.1; -; Genomic_DNA. DR EMBL; HQ204906; ADP90055.1; -; Genomic_DNA. DR EMBL; HQ204906; ADP90056.1; -; Genomic_DNA. DR EMBL; HQ204906; ADP90057.1; -; Genomic_DNA. DR EMBL; HQ204906; ADP90060.1; -; Genomic_DNA. DR EMBL; HQ204906; ADP90061.1; -; Genomic_DNA. DR EMBL; HQ204907; ADP90062.1; -; Genomic_DNA. DR EMBL; HQ204907; ADP90063.1; -; Genomic_DNA. DR EMBL; HQ204907; ADP90064.1; -; Genomic_DNA. DR EMBL; HQ204907; ADP90065.1; -; Genomic_DNA. DR EMBL; HQ204907; ADP90068.1; -; Genomic_DNA. DR EMBL; HQ204907; ADP90069.1; -; Genomic_DNA. DR EMBL; HQ204908; ADP90070.1; -; Genomic_DNA. DR EMBL; HQ204908; ADP90071.1; -; Genomic_DNA. DR EMBL; HQ204908; ADP90072.1; -; Genomic_DNA. DR EMBL; HQ204908; ADP90073.1; -; Genomic_DNA. DR EMBL; HQ204908; ADP90076.1; -; Genomic_DNA. DR EMBL; HQ204908; ADP90077.1; -; Genomic_DNA. DR EMBL; HQ204909; ADP90084.1; -; Genomic_DNA. DR EMBL; HQ204909; ADP90085.1; -; Genomic_DNA. DR EMBL; HQ204910; ADP90086.1; -; Genomic_DNA. DR EMBL; HQ204910; ADP90087.1; -; Genomic_DNA. DR EMBL; HQ204910; ADP90088.1; -; Genomic_DNA. DR EMBL; HQ204910; ADP90089.1; -; Genomic_DNA. DR EMBL; HQ204910; ADP90092.1; -; Genomic_DNA. DR EMBL; HQ204910; ADP90093.1; -; Genomic_DNA. DR EMBL; HQ204911; ADP90094.1; -; Genomic_DNA. DR EMBL; HQ204911; ADP90095.1; -; Genomic_DNA. DR EMBL; HQ204911; ADP90096.1; -; Genomic_DNA. DR EMBL; HQ204911; ADP90097.1; -; Genomic_DNA. DR EMBL; HQ204911; ADP90100.1; -; Genomic_DNA. DR EMBL; HQ204911; ADP90101.1; -; Genomic_DNA. DR EMBL; HQ204912; ADP90102.1; -; Genomic_DNA. DR EMBL; HQ204912; ADP90103.1; -; Genomic_DNA. DR EMBL; HQ204912; ADP90104.1; -; Genomic_DNA. DR EMBL; HQ204912; ADP90105.1; -; Genomic_DNA. DR EMBL; HQ204912; ADP90108.1; -; Genomic_DNA. DR EMBL; HQ204912; ADP90109.1; -; Genomic_DNA. DR EMBL; HQ204913; ADP90110.1; -; Genomic_DNA. DR EMBL; HQ204913; ADP90111.1; -; Genomic_DNA. DR EMBL; HQ204913; ADP90112.1; -; Genomic_DNA. DR EMBL; HQ204913; ADP90113.1; -; Genomic_DNA. DR EMBL; HQ204913; ADP90116.1; -; Genomic_DNA. DR EMBL; HQ204914; ADP90118.1; -; Genomic_DNA. DR EMBL; HQ204913; ADP90117.1; -; Genomic_DNA. DR EMBL; HQ204914; ADP90119.1; -; Genomic_DNA. DR EMBL; HQ204914; ADP90120.1; -; Genomic_DNA. DR EMBL; HQ204914; ADP90121.1; -; Genomic_DNA. DR EMBL; HQ204914; ADP90124.1; -; Genomic_DNA. DR EMBL; HQ204914; ADP90125.1; -; Genomic_DNA. DR EMBL; HQ204915; ADP90132.1; -; Genomic_DNA. DR EMBL; HQ204915; ADP90133.1; -; Genomic_DNA. DR EMBL; HQ204916; ADP90140.1; -; Genomic_DNA. DR EMBL; HQ204916; ADP90141.1; -; Genomic_DNA. DR EMBL; HQ204917; ADP90142.1; -; Genomic_DNA. DR EMBL; HQ204917; ADP90143.1; -; Genomic_DNA. DR EMBL; HQ204917; ADP90144.1; -; Genomic_DNA. DR EMBL; HQ204917; ADP90145.1; -; Genomic_DNA. DR EMBL; HQ204917; ADP90148.1; -; Genomic_DNA. DR EMBL; HQ204917; ADP90149.1; -; Genomic_DNA. DR EMBL; HQ204918; ADP90150.1; -; Genomic_DNA. DR EMBL; HQ204918; ADP90151.1; -; Genomic_DNA. DR EMBL; HQ204918; ADP90152.1; -; Genomic_DNA. DR EMBL; HQ204918; ADP90153.1; -; Genomic_DNA. DR EMBL; HQ204918; ADP90156.1; -; Genomic_DNA. DR EMBL; HQ204918; ADP90157.1; -; Genomic_DNA. DR EMBL; HQ204919; ADP90164.1; -; Genomic_DNA. DR EMBL; HQ204919; ADP90165.1; -; Genomic_DNA. DR EMBL; HQ204920; ADP90166.1; -; Genomic_DNA. DR EMBL; HQ204920; ADP90167.1; -; Genomic_DNA. DR EMBL; HQ204920; ADP90168.1; -; Genomic_DNA. DR EMBL; HQ204920; ADP90169.1; -; Genomic_DNA. DR EMBL; HQ204920; ADP90172.1; -; Genomic_DNA. DR EMBL; HQ204920; ADP90173.1; -; Genomic_DNA. DR EMBL; HQ204921; ADP90174.1; -; Genomic_DNA. DR EMBL; HQ204921; ADP90175.1; -; Genomic_DNA. DR EMBL; HQ204921; ADP90176.1; -; Genomic_DNA. DR EMBL; HQ204921; ADP90177.1; -; Genomic_DNA. DR EMBL; HQ204921; ADP90180.1; -; Genomic_DNA. DR EMBL; HQ204921; ADP90181.1; -; Genomic_DNA. DR EMBL; HQ204922; ADP90182.1; -; Genomic_DNA. DR EMBL; HQ204922; ADP90183.1; -; Genomic_DNA. DR EMBL; HQ204922; ADP90184.1; -; Genomic_DNA. DR EMBL; HQ204922; ADP90185.1; -; Genomic_DNA. DR EMBL; HQ204922; ADP90188.1; -; Genomic_DNA. DR EMBL; HQ204922; ADP90189.1; -; Genomic_DNA. DR EMBL; HQ204923; ADP90190.1; -; Genomic_DNA. DR EMBL; HQ204923; ADP90191.1; -; Genomic_DNA. DR EMBL; HQ204923; ADP90192.1; -; Genomic_DNA. DR EMBL; HQ204923; ADP90193.1; -; Genomic_DNA. DR EMBL; HQ204923; ADP90196.1; -; Genomic_DNA. DR EMBL; HQ204923; ADP90197.1; -; Genomic_DNA. DR EMBL; HQ204924; ADP90198.1; -; Genomic_DNA. DR EMBL; HQ204924; ADP90199.1; -; Genomic_DNA. DR EMBL; HQ204924; ADP90200.1; -; Genomic_DNA. DR EMBL; HQ204924; ADP90201.1; -; Genomic_DNA. DR EMBL; HQ204924; ADP90204.1; -; Genomic_DNA. DR EMBL; HQ204924; ADP90205.1; -; Genomic_DNA. DR EMBL; HQ204925; ADP90206.1; -; Genomic_DNA. DR EMBL; HQ204925; ADP90207.1; -; Genomic_DNA. DR EMBL; HQ204925; ADP90208.1; -; Genomic_DNA. DR EMBL; HQ204925; ADP90209.1; -; Genomic_DNA. DR EMBL; HQ204925; ADP90212.1; -; Genomic_DNA. DR EMBL; HQ204925; ADP90213.1; -; Genomic_DNA. DR EMBL; HQ204926; ADP90214.1; -; Genomic_DNA. DR EMBL; HQ204926; ADP90215.1; -; Genomic_DNA. DR EMBL; HQ204926; ADP90216.1; -; Genomic_DNA. DR EMBL; HQ204926; ADP90217.1; -; Genomic_DNA. DR EMBL; HQ204926; ADP90220.1; -; Genomic_DNA. DR EMBL; HQ204926; ADP90221.1; -; Genomic_DNA. DR EMBL; HQ204927; ADP90222.1; -; Genomic_DNA. DR EMBL; HQ204927; ADP90223.1; -; Genomic_DNA. DR EMBL; HQ204927; ADP90224.1; -; Genomic_DNA. DR EMBL; HQ204927; ADP90225.1; -; Genomic_DNA. DR EMBL; HQ204927; ADP90228.1; -; Genomic_DNA. DR EMBL; HQ204927; ADP90229.1; -; Genomic_DNA. DR EMBL; HQ204928; ADP90236.1; -; Genomic_DNA. DR EMBL; HQ204928; ADP90237.1; -; Genomic_DNA. DR EMBL; HQ204929; ADP90238.1; -; Genomic_DNA. DR EMBL; HQ204929; ADP90239.1; -; Genomic_DNA. DR EMBL; HQ204929; ADP90240.1; -; Genomic_DNA. DR EMBL; HQ204929; ADP90241.1; -; Genomic_DNA. DR EMBL; HQ204929; ADP90244.1; -; Genomic_DNA. DR EMBL; HQ204929; ADP90245.1; -; Genomic_DNA. DR EMBL; HQ204930; ADP90246.1; -; Genomic_DNA. DR EMBL; HQ204930; ADP90247.1; -; Genomic_DNA. DR EMBL; HQ204930; ADP90248.1; -; Genomic_DNA. DR EMBL; HQ204930; ADP90249.1; -; Genomic_DNA. DR EMBL; HQ204930; ADP90252.1; -; Genomic_DNA. DR EMBL; HQ204930; ADP90253.1; -; Genomic_DNA. DR EMBL; HQ204931; ADP90260.1; -; Genomic_DNA. DR EMBL; HQ204931; ADP90261.1; -; Genomic_DNA. DR EMBL; HQ204932; ADP90262.1; -; Genomic_DNA. DR EMBL; HQ204932; ADP90263.1; -; Genomic_DNA. DR EMBL; HQ204932; ADP90264.1; -; Genomic_DNA. DR EMBL; HQ204932; ADP90265.1; -; Genomic_DNA. DR EMBL; HQ204932; ADP90268.1; -; Genomic_DNA. DR EMBL; HQ204932; ADP90269.1; -; Genomic_DNA. DR EMBL; HQ204933; ADP90270.1; -; Genomic_DNA. DR EMBL; HQ204933; ADP90271.1; -; Genomic_DNA. DR EMBL; HQ204933; ADP90272.1; -; Genomic_DNA. DR EMBL; HQ204933; ADP90273.1; -; Genomic_DNA. DR EMBL; HQ204933; ADP90276.1; -; Genomic_DNA. DR EMBL; HQ204933; ADP90277.1; -; Genomic_DNA. DR EMBL; HQ204934; ADP90278.1; -; Genomic_DNA. DR EMBL; HQ204934; ADP90279.1; -; Genomic_DNA. DR EMBL; HQ204934; ADP90280.1; -; Genomic_DNA. DR EMBL; HQ204934; ADP90281.1; -; Genomic_DNA. DR EMBL; HQ204934; ADP90284.1; -; Genomic_DNA. DR EMBL; HQ204934; ADP90285.1; -; Genomic_DNA. DR EMBL; HQ204935; ADP90286.1; -; Genomic_DNA. DR EMBL; HQ204935; ADP90287.1; -; Genomic_DNA. DR EMBL; HQ204935; ADP90288.1; -; Genomic_DNA. DR EMBL; HQ204935; ADP90289.1; -; Genomic_DNA. DR EMBL; HQ204935; ADP90292.1; -; Genomic_DNA. DR EMBL; HQ204935; ADP90293.1; -; Genomic_DNA. DR EMBL; HQ204936; ADP90294.1; -; Genomic_DNA. DR EMBL; HQ204936; ADP90295.1; -; Genomic_DNA. DR EMBL; HQ204936; ADP90296.1; -; Genomic_DNA. DR EMBL; HQ204936; ADP90297.1; -; Genomic_DNA. DR EMBL; HQ204936; ADP90300.1; -; Genomic_DNA. DR EMBL; HQ204936; ADP90301.1; -; Genomic_DNA. DR EMBL; HQ204937; ADP90308.1; -; Genomic_DNA. DR EMBL; HQ204937; ADP90309.1; -; Genomic_DNA. DR EMBL; HQ204938; ADP90310.1; -; Genomic_DNA. DR EMBL; HQ204938; ADP90311.1; -; Genomic_DNA. DR EMBL; HQ204938; ADP90312.1; -; Genomic_DNA. DR EMBL; HQ204938; ADP90313.1; -; Genomic_DNA. DR EMBL; HQ204938; ADP90316.1; -; Genomic_DNA. DR EMBL; HQ204938; ADP90317.1; -; Genomic_DNA. DR EMBL; HQ204939; ADP90318.1; -; Genomic_DNA. DR EMBL; HQ204939; ADP90319.1; -; Genomic_DNA. DR EMBL; HQ204939; ADP90320.1; -; Genomic_DNA. DR EMBL; HQ204939; ADP90321.1; -; Genomic_DNA. DR EMBL; HQ204939; ADP90324.1; -; Genomic_DNA. DR EMBL; HQ204939; ADP90325.1; -; Genomic_DNA. DR EMBL; HQ204940; ADP90326.1; -; Genomic_DNA. DR EMBL; HQ204940; ADP90327.1; -; Genomic_DNA. DR EMBL; HQ204940; ADP90328.1; -; Genomic_DNA. DR EMBL; HQ204940; ADP90329.1; -; Genomic_DNA. DR EMBL; HQ204940; ADP90332.1; -; Genomic_DNA. DR EMBL; HQ204940; ADP90333.1; -; Genomic_DNA. DR EMBL; HQ204941; ADP90334.1; -; Genomic_DNA. DR EMBL; HQ204941; ADP90335.1; -; Genomic_DNA. DR EMBL; HQ204941; ADP90336.1; -; Genomic_DNA. DR EMBL; HQ204941; ADP90337.1; -; Genomic_DNA. DR EMBL; HQ204941; ADP90340.1; -; Genomic_DNA. DR EMBL; HQ204941; ADP90341.1; -; Genomic_DNA. DR EMBL; HQ204942; ADP90342.1; -; Genomic_DNA. DR EMBL; HQ204942; ADP90343.1; -; Genomic_DNA. DR EMBL; HQ204942; ADP90344.1; -; Genomic_DNA. DR EMBL; HQ204942; ADP90345.1; -; Genomic_DNA. DR EMBL; HQ204942; ADP90348.1; -; Genomic_DNA. DR EMBL; HQ204942; ADP90349.1; -; Genomic_DNA. DR EMBL; HQ204943; ADP90350.1; -; Genomic_DNA. DR EMBL; HQ204943; ADP90351.1; -; Genomic_DNA. DR EMBL; HQ204943; ADP90352.1; -; Genomic_DNA. DR EMBL; HQ204943; ADP90353.1; -; Genomic_DNA. DR EMBL; HQ204943; ADP90356.1; -; Genomic_DNA. DR EMBL; HQ204943; ADP90357.1; -; Genomic_DNA. DR EMBL; HQ204944; ADP90358.1; -; Genomic_DNA. DR EMBL; HQ204944; ADP90359.1; -; Genomic_DNA. DR EMBL; HQ204944; ADP90360.1; -; Genomic_DNA. DR EMBL; HQ204944; ADP90361.1; -; Genomic_DNA. DR EMBL; HQ204944; ADP90364.1; -; Genomic_DNA. DR EMBL; HQ204944; ADP90365.1; -; Genomic_DNA. DR EMBL; HQ204945; ADP90366.1; -; Genomic_DNA. DR EMBL; HQ204945; ADP90367.1; -; Genomic_DNA. DR EMBL; HQ204945; ADP90368.1; -; Genomic_DNA. DR EMBL; HQ204945; ADP90369.1; -; Genomic_DNA. DR EMBL; HQ204945; ADP90372.1; -; Genomic_DNA. DR EMBL; HQ204945; ADP90373.1; -; Genomic_DNA. DR EMBL; AC048351; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC106710; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78064.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78065.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78066.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78067.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78069.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78070.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78071.1; -; Genomic_DNA. DR EMBL; BC075805; AAH75805.1; -; mRNA. DR EMBL; AF416919; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF416920; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS33917.1; -. [O60313-2] DR CCDS; CCDS43186.1; -. [O60313-1] DR CCDS; CCDS87183.1; -. [O60313-13] DR PIR; T00336; T00336. DR RefSeq; NP_056375.2; NM_015560.2. [O60313-1] DR RefSeq; NP_570844.1; NM_130831.2. [O60313-13] DR RefSeq; NP_570846.1; NM_130833.2. [O60313-9] DR RefSeq; NP_570847.2; NM_130834.2. [O60313-11] DR RefSeq; NP_570849.2; NM_130836.2. [O60313-2] DR RefSeq; NP_570850.2; NM_130837.2. [O60313-10] DR PDB; 6JTG; X-ray; 2.40 A; A=263-571. DR PDB; 8CT1; EM; 4.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=1-960. DR PDB; 8CT9; EM; 6.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=1-960. DR PDB; 8EEW; EM; 5.48 A; A/B=195-960. DR PDB; 8EF7; EM; 9.68 A; A/B=195-960. DR PDB; 8EFF; EM; 5.48 A; A/B/C/D=195-960. DR PDB; 8EFR; EM; 5.48 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=195-960. DR PDB; 8EFS; EM; 9.68 A; A/B/C/D=195-960. DR PDB; 8EFT; EM; 9.68 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=195-960. DR PDBsum; 6JTG; -. DR PDBsum; 8CT1; -. DR PDBsum; 8CT9; -. DR PDBsum; 8EEW; -. DR PDBsum; 8EF7; -. DR PDBsum; 8EFF; -. DR PDBsum; 8EFR; -. DR PDBsum; 8EFS; -. DR PDBsum; 8EFT; -. DR AlphaFoldDB; O60313; -. DR EMDB; EMD-0722; -. DR EMDB; EMD-26977; -. DR EMDB; EMD-26984; -. DR EMDB; EMD-28063; -. DR EMDB; EMD-28074; -. DR EMDB; EMD-40192; -. DR EMDB; EMD-40193; -. DR EMDB; EMD-40197; -. DR EMDB; EMD-40198; -. DR EMDB; EMD-40200; -. DR EMDB; EMD-40202; -. DR EMDB; EMD-40203; -. DR EMDB; EMD-40204; -. DR EMDB; EMD-40210; -. DR EMDB; EMD-40211; -. DR EMDB; EMD-40212; -. DR EMDB; EMD-40213; -. DR EMDB; EMD-40214; -. DR EMDB; EMD-40215; -. DR EMDB; EMD-40216; -. DR EMDB; EMD-40217; -. DR EMDB; EMD-9901; -. DR EMDB; EMD-9902; -. DR EMDB; EMD-9903; -. DR SMR; O60313; -. DR BioGRID; 111024; 209. DR CORUM; O60313; -. DR IntAct; O60313; 56. DR MINT; O60313; -. DR STRING; 9606.ENSP00000354681; -. DR ChEMBL; CHEMBL4105705; -. DR TCDB; 1.N.6.1.2; the mitochondrial inner/outer membrane fusion (mmf) family. DR GlyGen; O60313; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O60313; -. DR PhosphoSitePlus; O60313; -. DR SwissPalm; O60313; -. DR BioMuta; OPA1; -. DR EPD; O60313; -. DR jPOST; O60313; -. DR MassIVE; O60313; -. DR MaxQB; O60313; -. DR PaxDb; 9606-ENSP00000354681; -. DR PeptideAtlas; O60313; -. DR ProteomicsDB; 15297; -. DR ProteomicsDB; 15298; -. DR ProteomicsDB; 15300; -. DR ProteomicsDB; 49340; -. [O60313-1] DR ProteomicsDB; 49341; -. [O60313-2] DR Pumba; O60313; -. DR Antibodypedia; 33885; 353 antibodies from 32 providers. DR DNASU; 4976; -. DR Ensembl; ENST00000361150.6; ENSP00000354781.2; ENSG00000198836.11. [O60313-9] DR Ensembl; ENST00000361510.8; ENSP00000355324.2; ENSG00000198836.11. [O60313-10] DR Ensembl; ENST00000361828.7; ENSP00000354429.3; ENSG00000198836.11. [O60313-1] DR Ensembl; ENST00000361908.8; ENSP00000354681.3; ENSG00000198836.11. [O60313-2] DR Ensembl; ENST00000392437.6; ENSP00000376232.2; ENSG00000198836.11. [O60313-11] DR Ensembl; ENST00000646793.1; ENSP00000494512.1; ENSG00000198836.11. [O60313-13] DR GeneID; 4976; -. DR KEGG; hsa:4976; -. DR MANE-Select; ENST00000361510.8; ENSP00000355324.2; NM_130837.3; NP_570850.2. [O60313-10] DR UCSC; uc003ftg.4; human. DR UCSC; uc003fti.3; human. [O60313-1] DR UCSC; uc003ftj.4; human. DR UCSC; uc003ftk.4; human. DR AGR; HGNC:8140; -. DR CTD; 4976; -. DR DisGeNET; 4976; -. DR GeneCards; OPA1; -. DR GeneReviews; OPA1; -. DR HGNC; HGNC:8140; OPA1. DR HPA; ENSG00000198836; Low tissue specificity. DR MalaCards; OPA1; -. DR MIM; 125250; phenotype. DR MIM; 165500; phenotype. DR MIM; 210000; phenotype. DR MIM; 605290; gene. DR MIM; 616896; phenotype. DR neXtProt; NX_O60313; -. DR OpenTargets; ENSG00000198836; -. DR Orphanet; 1215; Autosomal dominant optic atrophy plus syndrome. DR Orphanet; 98673; Autosomal dominant optic atrophy, classic form. DR PharmGKB; PA31927; -. DR VEuPathDB; HostDB:ENSG00000198836; -. DR eggNOG; KOG0447; Eukaryota. DR GeneTree; ENSGT00550000074851; -. DR InParanoid; O60313; -. DR OMA; ESQTDAF; -. DR OrthoDB; 48011at2759; -. DR PhylomeDB; O60313; -. DR TreeFam; TF314250; -. DR BRENDA; 3.6.5.5; 2681. DR PathwayCommons; O60313; -. DR Reactome; R-HSA-169911; Regulation of Apoptosis. DR SignaLink; O60313; -. DR SIGNOR; O60313; -. DR BioGRID-ORCS; 4976; 470 hits in 1165 CRISPR screens. DR ChiTaRS; OPA1; human. DR GeneWiki; Optic_atrophy_1; -. DR GenomeRNAi; 4976; -. DR Pharos; O60313; Tchem. DR PRO; PR:O60313; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O60313; Protein. DR Bgee; ENSG00000198836; Expressed in adrenal tissue and 205 other cell types or tissues. DR ExpressionAtlas; O60313; baseline and differential. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005874; C:microtubule; IBA:GO_Central. DR GO; GO:0030061; C:mitochondrial crista; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:ParkinsonsUK-UCL. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0031966; C:mitochondrial membrane; IBA:GO_Central. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:1901612; F:cardiolipin binding; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; NAS:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central. DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0019896; P:axonal transport of mitochondrion; TAS:UniProtKB. DR GO; GO:0090398; P:cellular senescence; IDA:UniProtKB. DR GO; GO:0046039; P:GTP metabolic process; IDA:UniProtKB. DR GO; GO:0007007; P:inner mitochondrial membrane organization; IDA:UniProtKB. DR GO; GO:0097749; P:membrane tubulation; IDA:UniProtKB. DR GO; GO:0000266; P:mitochondrial fission; TAS:UniProtKB. DR GO; GO:0008053; P:mitochondrial fusion; IDA:UniProtKB. DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IGI:ParkinsonsUK-UCL. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IMP:UniProtKB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:0007601; P:visual perception; IMP:UniProtKB. DR CDD; cd08771; DLP_1; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR022812; Dynamin. DR InterPro; IPR001401; Dynamin_GTPase. DR InterPro; IPR045063; Dynamin_N. DR InterPro; IPR030381; G_DYNAMIN_dom. DR InterPro; IPR045817; OPA1_C. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11566; DYNAMIN; 1. DR PANTHER; PTHR11566:SF67; DYNAMIN-LIKE 120 KDA PROTEIN, MITOCHONDRIAL; 1. DR Pfam; PF00350; Dynamin_N; 1. DR Pfam; PF19434; OPA1_C; 1. DR PRINTS; PR00195; DYNAMIN. DR SMART; SM00053; DYNc; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51718; G_DYNAMIN_2; 1. DR Genevisible; O60313; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cardiomyopathy; KW Coiled coil; Deafness; Disease variant; GTP-binding; Hydrolase; KW Lipid-binding; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Neurodegeneration; Nucleotide-binding; Primary mitochondrial disease; KW Reference proteome; Sensory transduction; Transit peptide; Transmembrane; KW Transmembrane helix; Vision. FT TRANSIT 1..87 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:Q2TA68" FT CHAIN 88..960 FT /note="Dynamin-like 120 kDa protein, mitochondrial" FT /id="PRO_0000007397" FT CHAIN 195..960 FT /note="Dynamin-like 120 kDa protein, form S1" FT /evidence="ECO:0000250|UniProtKB:Q2TA68" FT /id="PRO_0000253479" FT TOPO_DOM 88..96 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000250" FT TRANSMEM 97..113 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 114..960 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000250" FT DOMAIN 285..561 FT /note="Dynamin-type G" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 295..302 FT /note="G1 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 321..324 FT /note="G2 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 398..401 FT /note="G3 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 467..470 FT /note="G4 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 501..504 FT /note="G5 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT COILED 210..254 FT /evidence="ECO:0000255" FT COILED 895..960 FT /evidence="ECO:0000255" FT BINDING 295..302 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255" FT BINDING 398..402 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255" FT BINDING 467..470 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255" FT SITE 194..195 FT /note="Cleavage at site S1" FT /evidence="ECO:0000250|UniProtKB:Q2TA68" FT MOD_RES 228 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 150..185 FT /note="Missing (in isoform 3 and isoform 7)" FT /id="VSP_059072" FT VAR_SEQ 186 FT /note="G -> GHKLVSEVIGASDLLLLLG (in isoform 4 and isoform FT 5)" FT /id="VSP_059073" FT VAR_SEQ 206 FT /note="F -> FRKGLLGELILLQQQIQEHEEEARRAAGQYSTSYAQQK (in FT isoform 3 and isoform 4)" FT /id="VSP_059074" FT VAR_SEQ 209 FT /note="V -> GLLGELILLQQQIQEHEEEARRAAGQYSTSYAQQKRKV (in FT isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_021035" FT VARIANT 8 FT /note="A -> S (in OPA1; uncertain significance; FT dbSNP:rs794726939)" FT /evidence="ECO:0000269|PubMed:16617242" FT /id="VAR_060825" FT VARIANT 38..43 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:12036970" FT /id="VAR_022923" FT VARIANT 80 FT /note="Y -> C (in OPA1; dbSNP:rs151103940)" FT /evidence="ECO:0000269|PubMed:16617242" FT /id="VAR_060826" FT VARIANT 95 FT /note="T -> M (in OPA1; dbSNP:rs201214736)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060827" FT VARIANT 102 FT /note="Y -> C (in OPA1; dbSNP:rs530896300)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060828" FT VARIANT 158 FT /note="S -> N (in dbSNP:rs7624750)" FT /evidence="ECO:0000269|PubMed:11440988, FT ECO:0000269|PubMed:11440989, ECO:0000269|PubMed:12036970, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15948788, FT ECO:0000269|PubMed:16617242, ECO:0000269|PubMed:9628581" FT /id="VAR_022924" FT VARIANT 167 FT /note="P -> L (in dbSNP:rs754177232)" FT /evidence="ECO:0000269|PubMed:12036970" FT /id="VAR_022925" FT VARIANT 192 FT /note="A -> V (in dbSNP:rs34307082)" FT /evidence="ECO:0000269|PubMed:11440988, FT ECO:0000269|PubMed:12036970, ECO:0000269|PubMed:16617242" FT /id="VAR_022926" FT VARIANT 270 FT /note="E -> K (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060829" FT VARIANT 272 FT /note="L -> P (in OPA1)" FT /evidence="ECO:0000269|PubMed:14961560" FT /id="VAR_060830" FT VARIANT 273 FT /note="D -> A (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060831" FT VARIANT 290 FT /note="R -> Q (in OPA1; dbSNP:rs121908375)" FT /evidence="ECO:0000269|PubMed:11017080, FT ECO:0000269|PubMed:11440988, ECO:0000269|PubMed:11440989, FT ECO:0000269|PubMed:11810270" FT /id="VAR_011483" FT VARIANT 290 FT /note="R -> W (in OPA1; dbSNP:rs780333963)" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060832" FT VARIANT 293..294 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060833" FT VARIANT 300 FT /note="G -> E (in OPA1; loss of GTPase activity; loss of FT function in promoting mitochondrial fusion; FT dbSNP:rs28939082)" FT /evidence="ECO:0000269|PubMed:11017079, FT ECO:0000269|PubMed:11440989, ECO:0000269|PubMed:20185555" FT /id="VAR_011484" FT VARIANT 310 FT /note="Q -> R (in OPA1; dbSNP:rs770966290)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060834" FT VARIANT 324..326 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:15948788" FT /id="VAR_060835" FT VARIANT 330 FT /note="T -> S (in OPA1)" FT /evidence="ECO:0000269|PubMed:23401657" FT /id="VAR_072125" FT VARIANT 357 FT /note="A -> T (in DOA+ and OPA1; dbSNP:rs190223702)" FT /evidence="ECO:0000269|PubMed:18158317, FT ECO:0000269|PubMed:19319978" FT /id="VAR_060836" FT VARIANT 377 FT /note="V -> I (in OPA1; dbSNP:rs780922750)" FT /evidence="ECO:0000269|PubMed:23401657" FT /id="VAR_072126" FT VARIANT 382 FT /note="I -> M (in OPA1 and BEHRS; dbSNP:rs143319805)" FT /evidence="ECO:0000269|PubMed:19319978, FT ECO:0000269|PubMed:21636302, ECO:0000269|PubMed:25146916" FT /id="VAR_060837" FT VARIANT 384 FT /note="L -> F (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440989" FT /id="VAR_060838" FT VARIANT 396 FT /note="L -> P (in OPA1; dbSNP:rs727504060)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060839" FT VARIANT 396 FT /note="L -> R (in OPA1; dbSNP:rs727504060)" FT /evidence="ECO:0000269|PubMed:12036970" FT /id="VAR_022927" FT VARIANT 400 FT /note="P -> A (in OPA1)" FT /evidence="ECO:0000269|PubMed:22382025" FT /id="VAR_067355" FT VARIANT 402 FT /note="V -> M (in BEHRS; dbSNP:rs879255594)" FT /evidence="ECO:0000269|PubMed:25012220" FT /id="VAR_075903" FT VARIANT 429..430 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060840" FT VARIANT 430 FT /note="N -> D (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060841" FT VARIANT 432 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:11017080, FT ECO:0000269|PubMed:12036970" FT /id="VAR_011485" FT VARIANT 438 FT /note="D -> V (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060842" FT VARIANT 439 FT /note="G -> V (in DOA+ and OPA1; decreased GTPase activity; FT loss of function in promoting mitochondrial fusion; FT dbSNP:rs387906900)" FT /evidence="ECO:0000269|PubMed:18158317, FT ECO:0000269|PubMed:18204809, ECO:0000269|PubMed:20185555" FT /id="VAR_072127" FT VARIANT 445 FT /note="R -> H (in DOA+ and OPA1; decreased GTPase activity; FT loss of function in promoting mitochondrial fusion; FT dbSNP:rs80356529)" FT /evidence="ECO:0000269|PubMed:12566046, FT ECO:0000269|PubMed:15531309, ECO:0000269|PubMed:16240368, FT ECO:0000269|PubMed:18158317, ECO:0000269|PubMed:20185555" FT /id="VAR_015741" FT VARIANT 449 FT /note="T -> P (in DOA+)" FT /evidence="ECO:0000269|PubMed:23387428" FT /id="VAR_072128" FT VARIANT 449 FT /note="T -> R (in OPA1; dbSNP:rs1577244261)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060843" FT VARIANT 459 FT /note="G -> E (in OPA1)" FT /evidence="ECO:0000269|PubMed:22857269" FT /id="VAR_072129" FT VARIANT 463 FT /note="I -> IFIF (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060844" FT VARIANT 468 FT /note="K -> E (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060845" FT VARIANT 470 FT /note="D -> G (in OPA1)" FT /evidence="ECO:0000269|PubMed:14961560" FT /id="VAR_060846" FT VARIANT 487 FT /note="E -> K (in OPA1 and BEHRS)" FT /evidence="ECO:0000269|PubMed:19319978, FT ECO:0000269|PubMed:25012220" FT /id="VAR_060847" FT VARIANT 502 FT /note="V -> G" FT /evidence="ECO:0000269|PubMed:19969356" FT /id="VAR_072130" FT VARIANT 503 FT /note="T -> K (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440989, FT ECO:0000269|PubMed:12036970" FT /id="VAR_022928" FT VARIANT 505 FT /note="K -> N (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440989" FT /id="VAR_060848" FT VARIANT 534 FT /note="L -> R (in MTDPS14; dbSNP:rs869312995)" FT /evidence="ECO:0000269|PubMed:26561570" FT /id="VAR_075904" FT VARIANT 545 FT /note="S -> R (in DOA+ and OPA1; decreased GTPase activity; FT loss of function in promoting mitochondrial fusion; FT dbSNP:rs398124298)" FT /evidence="ECO:0000269|PubMed:16513463, FT ECO:0000269|PubMed:18065439, ECO:0000269|PubMed:18158317, FT ECO:0000269|PubMed:19319978, ECO:0000269|PubMed:20185555" FT /id="VAR_026533" FT VARIANT 550 FT /note="D -> N" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060849" FT VARIANT 551 FT /note="C -> Y (in OPA1 and DOA+; dbSNP:rs879255592)" FT /evidence="ECO:0000269|PubMed:19319978, FT ECO:0000269|PubMed:21112924" FT /id="VAR_060851" FT VARIANT 551 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:11440988" FT /id="VAR_060850" FT VARIANT 571 FT /note="R -> H (in OPA1; dbSNP:rs140606054)" FT /evidence="ECO:0000269|PubMed:12036970" FT /id="VAR_022929" FT VARIANT 574 FT /note="L -> P (in OPA1; dbSNP:rs1711513392)" FT /evidence="ECO:0000269|PubMed:14961560" FT /id="VAR_060852" FT VARIANT 582 FT /note="Y -> C (in DOA+; dbSNP:rs121908376)" FT /evidence="ECO:0000269|PubMed:18195150" FT /id="VAR_060853" FT VARIANT 586..589 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:12036970" FT /id="VAR_022930" FT VARIANT 590 FT /note="R -> Q (in OPA1; dbSNP:rs147077380)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060854" FT VARIANT 590 FT /note="R -> W (in OPA1; dbSNP:rs778998909)" FT /evidence="ECO:0000269|PubMed:15948788" FT /id="VAR_060855" FT VARIANT 593 FT /note="L -> P (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060856" FT VARIANT 593 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:19969356" FT /id="VAR_072131" FT VARIANT 646 FT /note="S -> L (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060857" FT VARIANT 700..701 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:14961560" FT /id="VAR_060858" FT VARIANT 728 FT /note="N -> K (in OPA1; loss of function in promoting FT mitochondrial fusion; dbSNP:rs1292852465)" FT /evidence="ECO:0000269|PubMed:15948788, FT ECO:0000269|PubMed:20185555" FT /id="VAR_060859" FT VARIANT 768 FT /note="G -> D (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060860" FT VARIANT 781 FT /note="R -> W (in OPA1; dbSNP:rs190235251)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060861" FT VARIANT 785 FT /note="Q -> R (in OPA1; loss of lipid binding and partial FT loss of function in promoting mitochondrial fusion; FT dbSNP:rs1064797302)" FT /evidence="ECO:0000269|PubMed:11440988, FT ECO:0000269|PubMed:11810270, ECO:0000269|PubMed:20185555" FT /id="VAR_060862" FT VARIANT 823 FT /note="S -> Y (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060863" FT VARIANT 841 FT /note="Y -> C (in OPA1)" FT /evidence="ECO:0000269|PubMed:16617242" FT /id="VAR_060864" FT VARIANT 882 FT /note="R -> L (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060865" FT VARIANT 887 FT /note="L -> P (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978" FT /id="VAR_060866" FT VARIANT 907 FT /note="E -> G (in dbSNP:rs863224138)" FT /evidence="ECO:0000269|PubMed:11440989" FT /id="VAR_060867" FT VARIANT 910 FT /note="V -> D (in DOA+; impairs protein folding; loss of FT function in promoting mitochondrial fusion; FT dbSNP:rs387906901)" FT /evidence="ECO:0000269|PubMed:18158317, FT ECO:0000269|PubMed:20185555" FT /id="VAR_072132" FT VARIANT 910 FT /note="Missing (in OPA1)" FT /evidence="ECO:0000269|PubMed:22857269" FT /id="VAR_072133" FT VARIANT 932 FT /note="R -> C (in OPA1; dbSNP:rs145710079)" FT /evidence="ECO:0000269|PubMed:19319978, FT ECO:0000269|PubMed:19325939" FT /id="VAR_060868" FT VARIANT 939 FT /note="L -> P (in OPA1; impairs protein folding; loss of FT function in promoting mitochondrial fusion)" FT /evidence="ECO:0000269|PubMed:11810270, FT ECO:0000269|PubMed:20185555" FT /id="VAR_028370" FT VARIANT 949 FT /note="L -> P (in OPA1)" FT /evidence="ECO:0000269|PubMed:19319978, FT ECO:0000269|PubMed:19969356" FT /id="VAR_060869" FT HELIX 264..274 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 291..296 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 301..309 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 327..333 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 338..341 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 353..370 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 382..388 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 394..398 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 414..426 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 432..438 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 443..445 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 449..455 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 460..467 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 469..475 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 479..486 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 490..492 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 496..500 FT /evidence="ECO:0007829|PDB:6JTG" FT STRAND 506..508 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 512..524 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 527..530 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 541..559 FT /evidence="ECO:0007829|PDB:6JTG" FT HELIX 561..571 FT /evidence="ECO:0007829|PDB:6JTG" FT MOTIF O60313-2:217..222 FT /note="LQQQIQ motif" FT /evidence="ECO:0000269|PubMed:16778770" FT VARIANT O60313-2:229 FT /note="R -> H (in OPA1) (Ref.28; dbSNP:rs138350727)" FT /evidence="ECO:0000269|PubMed:18360822" FT /id="VAR_082805" FT MOTIF O60313-9:181..186 FT /note="LQQQIQ motif" FT /evidence="ECO:0000269|PubMed:16778770" FT MOTIF O60313-10:235..240 FT /note="LQQQIQ motif" FT /evidence="ECO:0000269|PubMed:16778770" SQ SEQUENCE 960 AA; 111631 MW; 1C397109787AEB4D CRC64; MWRLRRAAVA CEVCQSLVKH SSGIKGSLPL QKLHLVSRSI YHSHHPTLKL QRPQLRTSFQ QFSSLTNLPL RKLKFSPIKY GYQPRRNFWP ARLATRLLKL RYLILGSAVG GGYTAKKTFD QWKDMIPDLS EYKWIVPDIV WEIDEYIDFE KIRKALPSSE DLVKLAPDFD KIVESLSLLK DFFTSGSPEE TAFRATDRGS ESDKHFRKVS DKEKIDQLQE ELLHTQLKYQ RILERLEKEN KELRKLVLQK DDKGIHHRKL KKSLIDMYSE VLDVLSDYDA SYNTQDHLPR VVVVGDQSAG KTSVLEMIAQ ARIFPRGSGE MMTRSPVKVT LSEGPHHVAL FKDSSREFDL TKEEDLAALR HEIELRMRKN VKEGCTVSPE TISLNVKGPG LQRMVLVDLP GVINTVTSGM APDTKETIFS ISKAYMQNPN AIILCIQDGS VDAERSIVTD LVSQMDPHGR RTIFVLTKVD LAEKNVASPS RIQQIIEGKL FPMKALGYFA VVTGKGNSSE SIEAIREYEE EFFQNSKLLK TSMLKAHQVT TRNLSLAVSD CFWKMVRESV EQQADSFKAT RFNLETEWKN NYPRLRELDR NELFEKAKNE ILDEVISLSQ VTPKHWEEIL QQSLWERVST HVIENIYLPA AQTMNSGTFN TTVDIKLKQW TDKQLPNKAV EVAWETLQEE FSRFMTEPKG KEHDDIFDKL KEAVKEESIK RHKWNDFAED SLRVIQHNAL EDRSISDKQQ WDAAIYFMEE ALQARLKDTE NAIENMVGPD WKKRWLYWKN RTQEQCVHNE TKNELEKMLK CNEEHPAYLA SDEITTVRKN LESRGVEVDP SLIKDTWHQV YRRHFLKTAL NHCNLCRRGF YYYQRHFVDS ELECNDVVLF WRIQRMLAIT ANTLRQQLTN TEVRRLEKNV KEVLEDFAED GEKKIKLLTG KRVQLAEDLK KVREIQEKLD AFIEALHQEK //