ID OMA1_HUMAN Reviewed; 524 AA. AC Q96E52; D3DQ54; Q5T3G6; Q5T3G7; Q5T3G8; Q5T3G9; Q5T3H0; Q8NBB3; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 02-SEP-2026, entry version 178. DE RecName: Full=Metalloendopeptidase OMA1, mitochondrial {ECO:0000305}; DE EC=3.4.24.- {ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}; DE AltName: Full=Metalloprotease-related protein 1 {ECO:0000303|PubMed:12886954}; DE Short=MPRP-1 {ECO:0000303|PubMed:12886954}; DE AltName: Full=Overlapping with the m-AAA protease 1 homolog {ECO:0000303|PubMed:20038677}; DE Flags: Precursor; GN Name=OMA1 {ECO:0000303|PubMed:20038677, ECO:0000312|HGNC:HGNC:29661}; GN Synonyms=MPRP1 {ECO:0000303|PubMed:12886954}; 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), AND TISSUE SPECIFICITY. RX PubMed=12886954; DOI=10.1093/dnares/10.3.123; RA Bao Y.-C., Tsuruga H., Hirai M., Yasuda K., Yokoi N., Kitamura T., RA Kumagai H.; RT "Identification of a human cDNA sequence which encodes a novel membrane- RT associated protein containing a zinc metalloprotease motif."; RL DNA Res. 10:123-128(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Liver; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-524 (ISOFORM 2). RC TISSUE=Substantia nigra; 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 [6] RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF RP HIS-331. 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 [7] RP FUNCTION. RX PubMed=25275009; DOI=10.1073/pnas.1417253111; RA Jiang X., Jiang H., Shen Z., Wang X.; RT "Activation of mitochondrial protease OMA1 by Bax and Bak promotes RT cytochrome c release during apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 111:14782-14787(2014). RN [8] RP FUNCTION. RX PubMed=25605331; DOI=10.1128/mcb.01047-14; RA Desmurs M., Foti M., Raemy E., Vaz F.M., Martinou J.C., Bairoch A., RA Lane L.; RT "C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 RT complex assembly and supercomplex stabilization."; RL Mol. Cell. Biol. 35:1139-1156(2015). RN [9] RP PROTEOLYTIC CLEAVAGE. RX PubMed=26923599; DOI=10.1016/j.celrep.2016.02.011; RA Rainbolt T.K., Lebeau J., Puchades C., Wiseman R.L.; RT "Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic RT Activity during Stress."; RL Cell Rep. 14:2041-2049(2016). RN [10] 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 [11] RP PROTEOLYTIC CLEAVAGE. RX PubMed=29545505; DOI=10.1242/jcs.213546; RA Consolato F., Maltecca F., Tulli S., Sambri I., Casari G.; RT "m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress- RT activated supervisor of mitochondrial dynamics."; RL J. Cell Sci. 131:0-0(2018). RN [12] RP REDOX-DEPENDENT REGULATION. RX PubMed=31044600; DOI=10.1089/ars.2018.7642; RA Bohovych I., Dietz J.V., Swenson S., Zahayko N., Khalimonchuk O.; RT "Redox regulation of the mitochondrial quality control protease Oma1."; RL Antioxid. Redox Signal. 31:429-443(2019). RN [13] RP FUNCTION, AND MUTAGENESIS OF GLU-328. RX PubMed=30733118; DOI=10.1016/j.molcel.2019.01.002; RA Sekine S., Wang C., Sideris D.P., Bunker E., Zhang Z., Youle R.J.; RT "Reciprocal roles of Tom7 and OMA1 during mitochondrial import and RT activation of PINK1."; RL Mol. Cell 73:1028-1043(2019). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF GLU-328. RX PubMed=32132706; DOI=10.1038/s41586-020-2076-4; RA Fessler E., Eckl E.M., Schmitt S., Mancilla I.A., Meyer-Bender M.F., RA Hanf M., Philippou-Massier J., Krebs S., Zischka H., Jae L.T.; RT "A pathway coordinated by DELE1 relays mitochondrial stress to the RT cytosol."; RL Nature 579:433-437(2020). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=32132707; DOI=10.1038/s41586-020-2078-2; RA Guo X., Aviles G., Liu Y., Tian R., Unger B.A., Lin Y.T., Wiita A.P., RA Xu K., Correia M.A., Kampmann M.; RT "Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI RT pathway."; RL Nature 579:427-432(2020). RN [16] RP FUNCTION. RX PubMed=31922487; DOI=10.7554/elife.50973; RA Ge Y., Shi X., Boopathy S., McDonald J., Smith A.W., Chao L.H.; RT "Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner- RT membrane."; RL Elife 9:0-0(2020). RN [17] RP VARIANT [LARGE SCALE ANALYSIS] VAL-226. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [18] RP VARIANTS TYR-69; LEU-117; GLY-272; LEU-329 AND TYR-365. RX PubMed=21220648; DOI=10.1001/archneurol.2010.351; RA Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D., RA Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A., RA Rouleau G.A.; RT "Resequencing of 29 candidate genes in patients with familial and sporadic RT amyotrophic lateral sclerosis."; RL Arch. Neurol. 68:587-593(2011). CC -!- FUNCTION: Metalloprotease that is part of the quality control system in CC the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, CC PubMed:32132706, PubMed:32132707). Activated in response to various CC mitochondrial stress, leading to the proteolytic cleavage of target CC proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, CC PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the CC fusion of the mitochondrial inner membranes by mediating cleavage of CC OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which CC cooperates with the membrane form (L-OPA1) to coordinate the fusion of CC mitochondrial inner membranes (PubMed:31922487). Following stress CC conditions that induce loss of mitochondrial membrane potential, CC mediates cleavage of OPA1, leading to excess production of soluble OPA1 CC (S-OPA1) and negative regulation of mitochondrial fusion CC (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard CC in response to transient mitochondrial membrane depolarization CC (flickering) by catalyzing cleavage of OPA1, leading to excess CC production of S-OPA1, preventing mitochondrial hyperfusion (By CC similarity). Also acts as a regulator of apoptosis: upon BAK and BAX CC aggregation, mediates cleavage of OPA1, leading to the remodeling of CC mitochondrial cristae and allowing the release of cytochrome c from CC mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, CC may also act as a backup protease for PINK1 by mediating PINK1 cleavage CC and promoting its subsequent degradation by the proteasome CC (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial CC depolarization (PubMed:25605331). Also acts as an activator of the CC integrated stress response (ISR): in response to mitochondrial stress, CC mediates cleavage of DELE1 to generate the processed form of DELE1 (S- CC DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to CC trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in CC mitochondrial quality control is essential for regulating lipid CC metabolism as well as to maintain body temperature and energy CC expenditure under cold-stress conditions (By similarity). Binds CC cardiolipin, possibly regulating its protein turnover (By similarity). CC Required for the stability of the respiratory supercomplexes (By CC similarity). {ECO:0000250|UniProtKB:Q9D8H7, CC ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, CC ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, CC ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, CC ECO:0000269|PubMed:32132707}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:O75844}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O75844}; CC -!- ACTIVITY REGULATION: Protease activity is activated upon autocatalytic CC cleavage in response to mitochondrial depolarization. CC {ECO:0000250|UniProtKB:Q9D8H7}. CC -!- SUBUNIT: Homooligomer. {ECO:0000250|UniProtKB:Q9D8H7}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:Q9D8H7}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96E52-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96E52-2; Sequence=VSP_027958; CC -!- TISSUE SPECIFICITY: Widely expressed, with strong expression in the CC heart, skeletal muscle, kidney and liver. CC {ECO:0000269|PubMed:12886954}. CC -!- DOMAIN: The stress-sensor region regulates proteolysis and activation. CC {ECO:0000250|UniProtKB:Q9D8H7}. CC -!- PTM: May form a redox-dependent disulfide bond (By similarity). Exists CC in a semi-oxidized state and is activated by prolonged hypoxia CC (PubMed:31044600). {ECO:0000250|UniProtKB:P36163, CC ECO:0000269|PubMed:31044600}. CC -!- PTM: Autocatalytically cleaved in response to mitochondrial CC depolarization both at the N-terminus and C-terminus to generate the CC short active form (S-OMA1) (By similarity). Autocatalytic processing at CC the C-terminus takes place at residues 447-456 (By similarity). The S- CC OMA1 form is unstable (By similarity). OMA1 pre-processing by AFG3L2 CC may participate in maturation before OMA1 autocatalytic cleavage CC (PubMed:29545505). Degraded by YMEL1 in response to membrane CC depolarization (PubMed:26923599). Protein turnover is regulated by CC prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a CC cardiolipin-binding manner (By similarity). CC {ECO:0000250|UniProtKB:Q9D8H7, ECO:0000269|PubMed:26923599, CC ECO:0000269|PubMed:29545505}. CC -!- SIMILARITY: Belongs to the peptidase M48 family. {ECO:0000305}. CC -!- CAUTION: Was initially reported to localize in the endoplasmic CC reticulum (PubMed:12886954). However, it was later shown that it CC localizes to mitochondrion (PubMed:20038677). CC {ECO:0000305|PubMed:12886954, ECO:0000305|PubMed:20038677}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC03583.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AB048348; BAC79381.1; -; mRNA. DR EMBL; AL109845; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL365187; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06631.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06632.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06633.1; -; Genomic_DNA. DR EMBL; BC012915; AAH12915.1; -; mRNA. DR EMBL; AK091101; BAC03583.1; ALT_INIT; mRNA. DR CCDS; CCDS608.1; -. [Q96E52-1] DR RefSeq; NP_660286.1; NM_145243.5. [Q96E52-1] DR AlphaFoldDB; Q96E52; -. DR SMR; Q96E52; -. DR BioGRID; 125420; 164. DR FunCoup; Q96E52; 730. DR IntAct; Q96E52; 152. DR MINT; Q96E52; -. DR STRING; 9606.ENSP00000360270; -. DR MEROPS; M48.017; -. DR TCDB; 8.A.150.1.1; the mitochondrial metalloendopeptidase oma1 (oma1) family. DR GlyGen; Q96E52; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96E52; -. DR PhosphoSitePlus; Q96E52; -. DR SwissPalm; Q96E52; -. DR BioMuta; OMA1; -. DR DMDM; 74751828; -. DR jPOST; Q96E52; -. DR MassIVE; Q96E52; -. DR PaxDb; 9606-ENSP00000360270; -. DR PeptideAtlas; Q96E52; -. DR ProteomicsDB; 76375; -. [Q96E52-1] DR ProteomicsDB; 76376; -. [Q96E52-2] DR Pumba; Q96E52; -. DR Antibodypedia; 46900; 88 antibodies from 25 providers. DR DNASU; 115209; -. DR Ensembl; ENST00000371226.8; ENSP00000360270.3; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906297.1; ENSP00000576356.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906298.1; ENSP00000576357.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906300.1; ENSP00000576359.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906301.1; ENSP00000576360.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906302.1; ENSP00000576361.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906303.1; ENSP00000576362.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906304.1; ENSP00000576363.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906306.1; ENSP00000576365.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906307.1; ENSP00000576366.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906308.1; ENSP00000576367.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906309.1; ENSP00000576368.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000906310.1; ENSP00000576369.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000929571.1; ENSP00000599630.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000929572.1; ENSP00000599631.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000929573.1; ENSP00000599632.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000929574.1; ENSP00000599633.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000963342.1; ENSP00000633401.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000963343.1; ENSP00000633402.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000963344.1; ENSP00000633403.1; ENSG00000162600.13. [Q96E52-1] DR Ensembl; ENST00000963345.1; ENSP00000633404.1; ENSG00000162600.13. [Q96E52-1] DR GeneID; 115209; -. DR KEGG; hsa:115209; -. DR MANE-Select; ENST00000371226.8; ENSP00000360270.3; NM_145243.5; NP_660286.1. DR UCSC; uc001cyy.4; human. [Q96E52-1] DR AGR; HGNC:29661; -. DR ClinPGx; PA134911478; -. DR CTD; 115209; -. DR DisGeNET; 115209; -. DR GeneCards; OMA1; -. DR HGNC; HGNC:29661; OMA1. DR HPA; ENSG00000162600; Low tissue specificity. DR OpenTargets; ENSG00000162600; -. DR VEuPathDB; HostDB:ENSG00000162600; -. DR eggNOG; KOG2661; Eukaryota. DR GeneTree; ENSGT00390000007027; -. DR HOGENOM; CLU_039633_0_0_1; -. DR InParanoid; Q96E52; -. DR OMA; TFILGHE; -. DR OrthoDB; 7464992at2759; -. DR PAN-GO; Q96E52; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q96E52; -. DR PathwayCommons; Q96E52; -. DR Reactome; R-HSA-169911; Regulation of Apoptosis. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR Reactome; R-HSA-9840373; Cellular response to mitochondrial stress. DR SignaLink; Q96E52; -. DR SIGNOR; Q96E52; -. DR Agora; ENSG00000162600; -. DR BioGRID-ORCS; 115209; 12 hits in 1160 CRISPR screens. DR ChiTaRS; OMA1; human. DR GenomeRNAi; 115209; -. DR Pharos; Q96E52; Tbio. DR PRO; PR:Q96E52; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q96E52; protein. DR Bgee; ENSG00000162600; Expressed in bronchial epithelial cell and 184 other cell types or tissues. DR ExpressionAtlas; Q96E52; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProt. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB. DR GO; GO:0033554; P:cellular response to stress; IDA:UniProt. DR GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; ISS:UniProtKB. DR GO; GO:0140468; P:HRI-mediated signaling; IDA:UniProtKB. DR GO; GO:0140467; P:integrated stress response signaling; IDA:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB. DR GO; GO:1990627; P:mitochondrial inner membrane fusion; ISS:UniProt. DR GO; GO:0034982; P:mitochondrial protein processing; IDA:UniProtKB. DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; ISS:UniProtKB. DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB. DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:UniProtKB. DR GO; GO:1903850; P:regulation of cristae formation; IDA:UniProtKB. DR GO; GO:0031638; P:zymogen activation; ISS:UniProtKB. DR CDD; cd07331; M48C_Oma1_like; 1. DR FunFam; 3.30.2010.10:FF:000009; metalloendopeptidase OMA1, mitochondrial isoform X1; 1. DR Gene3D; 3.30.2010.10; Metalloproteases ('zincins'), catalytic domain; 1. DR InterPro; IPR051156; Mito/Outer_Membr_Metalloprot. DR InterPro; IPR001915; Peptidase_M48. DR PANTHER; PTHR22726; METALLOENDOPEPTIDASE OMA1; 1. DR PANTHER; PTHR22726:SF1; METALLOENDOPEPTIDASE OMA1, MITOCHONDRIAL; 1. DR Pfam; PF01435; Peptidase_M48; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW Alternative splicing; Autocatalytic cleavage; Disulfide bond; Hydrolase; KW Lipid-binding; Membrane; Metal-binding; Metalloprotease; Mitochondrion; KW Mitochondrion inner membrane; Protease; Proteomics identification; KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix; KW Zinc; Zymogen. FT TRANSIT 1..13 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT PROPEP 14..143 FT /evidence="ECO:0000250|UniProtKB:Q9D8H7" FT /id="PRO_0000450313" FT CHAIN 144..? FT /note="Metalloendopeptidase OMA1, mitochondrial" FT /id="PRO_0000302809" FT PROPEP ?..524 FT /evidence="ECO:0000250|UniProtKB:Q9D8H7" FT /id="PRO_0000450314" FT TOPO_DOM 144..195 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000250|UniProtKB:Q9D8H7" FT TRANSMEM 196..216 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 217..? FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000250|UniProtKB:Q9D8H7" FT REGION 148..167 FT /note="Cardiolipin-binding" FT /evidence="ECO:0000250|UniProtKB:Q9D8H7" FT REGION 165..195 FT /note="Stress-sensor region" FT /evidence="ECO:0000250|UniProtKB:Q9D8H7" FT ACT_SITE 328 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, FT ECO:0000305|PubMed:32132706" FT BINDING 327 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 331 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:O75844" FT BINDING 392 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT DISULFID 407..465 FT /evidence="ECO:0000250|UniProtKB:P36163" FT VAR_SEQ 456..524 FT /note="ALKIREMCNCPPLSNPDPRLLFKLSTKHFLEESEKEDLNITKKQKMDTLPIQ FT KQEQIPLTYIVEKRTGS -> LVREEKFIEQPEQIAELTLNSFIQNTEICRS (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_027958" FT VARIANT 67 FT /note="N -> K (in dbSNP:rs34466938)" FT /id="VAR_034958" FT VARIANT 69 FT /note="H -> Y (in a patient with amyotrophic lateral FT sclerosis; dbSNP:rs75220198)" FT /evidence="ECO:0000269|PubMed:21220648" FT /id="VAR_065755" FT VARIANT 117 FT /note="P -> L (in dbSNP:rs17117720)" FT /evidence="ECO:0000269|PubMed:21220648" FT /id="VAR_034959" FT VARIANT 211 FT /note="F -> C (in dbSNP:rs17117699)" FT /id="VAR_034960" FT VARIANT 226 FT /note="L -> V (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035708" FT VARIANT 272 FT /note="E -> G (in a patient with amyotrophic lateral FT sclerosis; dbSNP:rs139938730)" FT /evidence="ECO:0000269|PubMed:21220648" FT /id="VAR_065756" FT VARIANT 329 FT /note="I -> L (in dbSNP:rs17117678)" FT /evidence="ECO:0000269|PubMed:21220648" FT /id="VAR_034961" FT VARIANT 365 FT /note="D -> Y (in dbSNP:rs77980955)" FT /evidence="ECO:0000269|PubMed:21220648" FT /id="VAR_065757" FT MUTAGEN 328 FT /note="E->Q: Abolished protease activity and ability to FT mediate cleavage of DELE1 in response to mitochondrial FT stress. Abolished ability to mediate cleavage of PINK1 in FT depolarized mitochondria." FT /evidence="ECO:0000269|PubMed:30733118, FT ECO:0000269|PubMed:32132706" FT MUTAGEN 331 FT /note="H->A: Abolishes ability to cleave OPA1 at S1 FT position." FT /evidence="ECO:0000269|PubMed:20038677" SQ SEQUENCE 524 AA; 60120 MW; F8F9B37489B0EFF1 CRC64; MSFICGLQSA ARNHVFFRFN SLSNWRKCNT LASTSRGCHQ VQVNHIVNKY QGLGVNQCDR WSFLPGNFHF YSTFNNKRTG GLSSTKSKEI WRITSKCTVW NDAFSRQLLI KEVTAVPSLS VLHPLSPASI RAIRNFHTSP RFQAAPVPLL LMILKPVQKL FAIIVGRGIR KWWQALPPNK KEVVKENIRK NKWKLFLGLS SFGLLFVVFY FTHLEVSPIT GRSKLLLLGK EQFRLLSELE YEAWMEEFKN DMLTEKDARY LAVKEVLCHL IECNKDVPGI SQINWVIHVV DSPIINAFVL PNGQMFVFTG FLNSVTDIHQ LSFLLGHEIA HAVLGHAAEK AGMVHLLDFL GMIFLTMIWA ICPRDSLALL CQWIQSKLQE YMFNRPYSRK LEAEADKIGL LLAAKACADI RASSVFWQQM EFVDSLHGQP KMPEWLSTHP SHGNRVEYLD RLIPQALKIR EMCNCPPLSN PDPRLLFKLS TKHFLEESEK EDLNITKKQK MDTLPIQKQE QIPLTYIVEK RTGS //