OPA3_HUMAN
ID OPA3_HUMAN Reviewed; 179 AA.
AC Q9H6K4; Q6P384; Q8N784;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Optic atrophy 3 protein;
GN Name=OPA3;
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] (ISOFORM 1), INVOLVEMENT IN MGCA3, AND TISSUE
RP SPECIFICITY.
RX PubMed=11668429; DOI=10.1086/324651;
RA Anikster Y., Kleta R., Shaag A., Gahl W.A., Elpeleg O.;
RT "Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or
RT Costeff optic atrophy syndrome): identification of the OPA3 gene and its
RT founder mutation in Iraqi Jews.";
RL Am. J. Hum. Genet. 69:1218-1224(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, Lung, and Testis;
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 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 [5]
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 [6]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP 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 [7]
RP VARIANTS OPA3 SER-93 AND GLU-105.
RX PubMed=15342707; DOI=10.1136/jmg.2003.016576;
RA Reynier P., Amati-Bonneau P., Verny C., Olichon A., Simard G., Guichet A.,
RA Bonnemains C., Malecaze F., Malinge M.C., Pelletier J.B., Calvas P.,
RA Dollfus H., Belenguer P., Malthiery Y., Lenaers G., Bonneau D.;
RT "OPA3 gene mutations responsible for autosomal dominant optic atrophy and
RT cataract.";
RL J. Med. Genet. 41:E110-E110(2004).
RN [8]
RP VARIANT ARG-15.
RX PubMed=31696227; DOI=10.1093/hmg/ddz268;
RA Atac D., Koller S., Hanson J.V.M., Feil S., Tiwari A., Bahr A., Baehr L.,
RA Magyar I., Kottke R., Gerth-Kahlert C., Berger W.;
RT "Atonal homolog 7 (ATOH7) loss-of-function mutations in predominant
RT bilateral optic nerve hypoplasia.";
RL Hum. Mol. Genet. 29:132-148(2020).
CC -!- FUNCTION: May play some role in mitochondrial processes.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=The two isoforms share the first coding exon and than differ
CC due to a duplicated alternative second coding exon.;
CC Name=1;
CC IsoId=Q9H6K4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H6K4-2; Sequence=VSP_032681;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Most prominent expression in skeletal
CC muscle and kidney. {ECO:0000269|PubMed:11668429}.
CC -!- DISEASE: 3-methylglutaconic aciduria 3 (MGCA3) [MIM:258501]: An
CC autosomal recessive metabolic disorder that causes a neuro-
CC ophthalmologic syndrome consisting of early-onset bilateral optic
CC atrophy, spasticity, extrapyramidal dysfunction and cognitive deficit.
CC Urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid
CC is increased. MGCA3 can be distinguished from MGCA1 by the absence of
CC increase of 3-hydroxyisovaleric acid levels.
CC {ECO:0000269|PubMed:11668429}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Optic atrophy 3 (OPA3) [MIM:165300]: 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. OPA3 is associated with cataract
CC and a neurologic disorder characterized by extrapyramidal signs and
CC ataxia. {ECO:0000269|PubMed:15342707}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the OPA3 family. {ECO:0000305}.
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DR EMBL; AK025840; BAB15255.1; -; mRNA.
DR EMBL; AK098798; BAC05415.1; -; mRNA.
DR EMBL; BC005059; AAH05059.1; -; mRNA.
DR EMBL; BC047316; AAH47316.1; -; mRNA.
DR EMBL; BC064146; AAH64146.1; -; mRNA.
DR CCDS; CCDS12668.1; -. [Q9H6K4-1]
DR CCDS; CCDS33052.1; -. [Q9H6K4-2]
DR RefSeq; NP_001017989.2; NM_001017989.2. [Q9H6K4-2]
DR RefSeq; NP_079412.1; NM_025136.3. [Q9H6K4-1]
DR AlphaFoldDB; Q9H6K4; -.
DR SMR; Q9H6K4; -.
DR BioGRID; 123176; 46.
DR IntAct; Q9H6K4; 89.
DR MINT; Q9H6K4; -.
DR iPTMnet; Q9H6K4; -.
DR PhosphoSitePlus; Q9H6K4; -.
DR BioMuta; OPA3; -.
DR DMDM; 20139177; -.
DR EPD; Q9H6K4; -.
DR jPOST; Q9H6K4; -.
DR MassIVE; Q9H6K4; -.
DR MaxQB; Q9H6K4; -.
DR PeptideAtlas; Q9H6K4; -.
DR PRIDE; Q9H6K4; -.
DR ProteomicsDB; 80995; -. [Q9H6K4-1]
DR ProteomicsDB; 80996; -. [Q9H6K4-2]
DR TopDownProteomics; Q9H6K4-1; -. [Q9H6K4-1]
DR Antibodypedia; 31359; 206 antibodies from 25 providers.
DR DNASU; 80207; -.
DR Ensembl; ENST00000263275.5; ENSP00000263275.4; ENSG00000125741.5. [Q9H6K4-1]
DR Ensembl; ENST00000323060.3; ENSP00000319817.3; ENSG00000125741.5. [Q9H6K4-2]
DR GeneID; 80207; -.
DR KEGG; hsa:80207; -.
DR MANE-Select; ENST00000263275.5; ENSP00000263275.4; NM_025136.4; NP_079412.1.
DR UCSC; uc002pcj.5; human. [Q9H6K4-1]
DR CTD; 80207; -.
DR DisGeNET; 80207; -.
DR GeneCards; OPA3; -.
DR GeneReviews; OPA3; -.
DR HGNC; HGNC:8142; OPA3.
DR HPA; ENSG00000125741; Low tissue specificity.
DR MalaCards; OPA3; -.
DR MIM; 165300; phenotype.
DR MIM; 258501; phenotype.
DR MIM; 606580; gene.
DR neXtProt; NX_Q9H6K4; -.
DR OpenTargets; ENSG00000125741; -.
DR Orphanet; 67047; 3-methylglutaconic aciduria type 3.
DR Orphanet; 67036; Autosomal dominant optic atrophy and cataract.
DR PharmGKB; PA31929; -.
DR VEuPathDB; HostDB:ENSG00000125741; -.
DR GeneTree; ENSGT00390000009795; -.
DR HOGENOM; CLU_074707_5_1_1; -.
DR InParanoid; Q9H6K4; -.
DR OMA; KTYVCLP; -.
DR OrthoDB; 1444400at2759; -.
DR PhylomeDB; Q9H6K4; -.
DR TreeFam; TF314653; -.
DR PathwayCommons; Q9H6K4; -.
DR SignaLink; Q9H6K4; -.
DR BioGRID-ORCS; 80207; 15 hits in 1073 CRISPR screens.
DR ChiTaRS; OPA3; human.
DR GeneWiki; OPA3; -.
DR GenomeRNAi; 80207; -.
DR Pharos; Q9H6K4; Tbio.
DR PRO; PR:Q9H6K4; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H6K4; protein.
DR Bgee; ENSG00000125741; Expressed in tendon of biceps brachii and 134 other tissues.
DR ExpressionAtlas; Q9H6K4; baseline and differential.
DR Genevisible; Q9H6K4; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:LIFEdb.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR InterPro; IPR010754; OPA3-like.
DR PANTHER; PTHR12499; PTHR12499; 1.
DR Pfam; PF07047; OPA3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Coiled coil; Disease variant;
KW Mitochondrion; Reference proteome; Sensory transduction; Vision.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..179
FT /note="Optic atrophy 3 protein"
FT /id="PRO_0000220763"
FT COILED 103..163
FT /evidence="ECO:0000255"
FT VAR_SEQ 52..179
FT /note="VEMRTKMRIMGFRGTVIKPLNEEAAAELGAELLGEATIFIVGGGCLVLEYWR
FT HQAQQRHKEEEQRAAWNALRDEVGHLALALEALQAQVQAAPPQGALEELRTELQEVRAQ
FT LCNPGRSASHAVPASKK -> LEMRTKMRIMGFNAAAIKPLNEGAAAELGAELLGEGII
FT FITACSCLMLEYWRHQLQQRRKEKERRVAREALRGEVGHLGLALEELQAQVQATSTQLA
FT LEELRAQLQEVRAHLCLRDPPPAPPVAPASEK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_032681"
FT VARIANT 15
FT /note="G -> R (found in a family with foveal hypoplasia;
FT unknown pathological significance; dbSNP:rs771522612)"
FT /evidence="ECO:0000269|PubMed:31696227"
FT /id="VAR_085736"
FT VARIANT 93
FT /note="G -> S (in OPA3; dbSNP:rs80356524)"
FT /evidence="ECO:0000269|PubMed:15342707"
FT /id="VAR_033103"
FT VARIANT 105
FT /note="Q -> E (in OPA3; dbSNP:rs80356525)"
FT /evidence="ECO:0000269|PubMed:15342707"
FT /id="VAR_033104"
FT CONFLICT Q9H6K4-2:130
FT /note="G -> E (in Ref. 2; BAC05415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 179 AA; 19996 MW; 2FB48F84B24E5AE8 CRC64;
MVVGAFPMAK LLYLGIRQVS KPLANRIKEA ARRSEFFKTY ICLPPAQLYH WVEMRTKMRI
MGFRGTVIKP LNEEAAAELG AELLGEATIF IVGGGCLVLE YWRHQAQQRH KEEEQRAAWN
ALRDEVGHLA LALEALQAQV QAAPPQGALE ELRTELQEVR AQLCNPGRSA SHAVPASKK
