OMA1_HUMAN
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 03-AUG-2022, entry version 159.
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 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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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). Following stress
CC conditions that induce loss of mitochondrial membrane potential,
CC mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation
CC and negative regulation of mitochondrial fusion (PubMed:20038677,
CC PubMed:25275009). Also acts as a regulator of apoptosis: upon BAK and
CC BAX aggregation, mediates cleavage of OPA1, leading to the remodeling
CC of 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:32132706, 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). Degradaded by YMEL1 in response
CC to membrane depolarization (PubMed:26923599). Protein turnover is
CC regulated by prohibitin (PHB and PHB2), which promotes degradation of
CC OMA1 in a cardiolipin-binding manner (By similarity).
CC {ECO:0000250|UniProtKB:Q9D8H7, ECO:0000269|PubMed:26923599}.
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};
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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_145243.4. [Q96E52-1]
DR AlphaFoldDB; Q96E52; -.
DR SMR; Q96E52; -.
DR BioGRID; 125420; 143.
DR IntAct; Q96E52; 103.
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 iPTMnet; Q96E52; -.
DR PhosphoSitePlus; Q96E52; -.
DR SwissPalm; Q96E52; -.
DR BioMuta; OMA1; -.
DR DMDM; 74751828; -.
DR EPD; Q96E52; -.
DR jPOST; Q96E52; -.
DR MassIVE; Q96E52; -.
DR MaxQB; Q96E52; -.
DR PaxDb; Q96E52; -.
DR PeptideAtlas; Q96E52; -.
DR PRIDE; Q96E52; -.
DR ProteomicsDB; 76375; -. [Q96E52-1]
DR ProteomicsDB; 76376; -. [Q96E52-2]
DR Antibodypedia; 46900; 96 antibodies from 25 providers.
DR DNASU; 115209; -.
DR Ensembl; ENST00000371226.8; ENSP00000360270.3; ENSG00000162600.12. [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 CTD; 115209; -.
DR DisGeNET; 115209; -.
DR GeneCards; OMA1; -.
DR HGNC; HGNC:29661; OMA1.
DR HPA; ENSG00000162600; Low tissue specificity.
DR neXtProt; NX_Q96E52; -.
DR OpenTargets; ENSG00000162600; -.
DR PharmGKB; PA134911478; -.
DR VEuPathDB; HostDB:ENSG00000162600; -.
DR eggNOG; KOG2661; Eukaryota.
DR GeneTree; ENSGT00390000007027; -.
DR HOGENOM; CLU_039633_0_0_1; -.
DR InParanoid; Q96E52; -.
DR OMA; ILGQWIQ; -.
DR OrthoDB; 960152at2759; -.
DR PhylomeDB; Q96E52; -.
DR TreeFam; TF329133; -.
DR PathwayCommons; Q96E52; -.
DR Reactome; R-HSA-169911; Regulation of Apoptosis.
DR SignaLink; Q96E52; -.
DR BioGRID-ORCS; 115209; 12 hits in 1081 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 182 other tissues.
DR ExpressionAtlas; Q96E52; baseline and differential.
DR Genevisible; Q96E52; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042407; P:cristae formation; IEA:Ensembl.
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: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:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome.
DR GO; GO:1903850; P:regulation of cristae formation; IDA:UniProtKB.
DR GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR InterPro; IPR001915; Peptidase_M48.
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; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix; 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
