OMA1_YEAST
ID OMA1_YEAST Reviewed; 345 AA.
AC P36163; D6VXE7;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Mitochondrial metalloendopeptidase OMA1 {ECO:0000305};
DE EC=3.4.24.- {ECO:0000269|PubMed:12963738, ECO:0000269|PubMed:22219186, ECO:0000269|PubMed:24648523};
GN Name=OMA1 {ECO:0000312|SGD:S000001795}; OrderedLocusNames=YKR087C;
GN ORFNames=YKR407;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8203164; DOI=10.1002/yea.320100210;
RA Garcia-Cantalejo J.M., Baladron V., Esteban P.F., Santos M.A., Bou G.,
RA Remacha M.A., Revuelta J.L., Ballesta J.P.G., Jimenez A., del Rey F.;
RT "The complete sequence of an 18,002 bp segment of Saccharomyces cerevisiae
RT chromosome XI contains the HBS1, MRP-L20 and PRP16 genes, and six new open
RT reading frames.";
RL Yeast 10:231-245(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-204; HIS-207 AND
RP HIS-212.
RX PubMed=12963738; DOI=10.1074/jbc.m305584200;
RA Kaeser M., Kambacheld M., Kisters-Woike B., Langer T.;
RT "Oma1, a novel membrane-bound metallopeptidase in mitochondria with
RT activities overlapping with the m-AAA protease.";
RL J. Biol. Chem. 278:46414-46423(2003).
RN [5]
RP IDENTIFICATION OF FRAMESHIFT.
RX PubMed=12748633; DOI=10.1038/nature01644;
RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.;
RT "Sequencing and comparison of yeast species to identify genes and
RT regulatory elements.";
RL Nature 423:241-254(2003).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP FUNCTION.
RX PubMed=22219186; DOI=10.1074/jbc.m111.313148;
RA Khalimonchuk O., Jeong M.Y., Watts T., Ferris E., Winge D.R.;
RT "Selective Oma1 protease-mediated proteolysis of Cox1 subunit of cytochrome
RT oxidase in assembly mutants.";
RL J. Biol. Chem. 287:7289-7300(2012).
RN [8]
RP FUNCTION, SUBUNIT, ACTIVITY REGULATION, DISRUPTION PHENOTYPE, ACTIVE SITE,
RP AND MUTAGENESIS OF HIS-203 AND GLU-204.
RX PubMed=24648523; DOI=10.1074/jbc.m113.542910;
RA Bohovych I., Donaldson G., Christianson S., Zahayko N., Khalimonchuk O.;
RT "Stress-triggered activation of the metalloprotease Oma1 involves its C-
RT terminal region and is important for mitochondrial stress protection in
RT yeast.";
RL J. Biol. Chem. 289:13259-13272(2014).
RN [9]
RP FUNCTION.
RX PubMed=26365306; DOI=10.1038/srep13989;
RA Bohovych I., Fernandez M.R., Rahn J.J., Stackley K.D., Bestman J.E.,
RA Anandhan A., Franco R., Claypool S.M., Lewis R.E., Chan S.S.,
RA Khalimonchuk O.;
RT "metalloprotease OMA1 fine-tunes mitochondrial bioenergetic function and
RT respiratory supercomplex stability.";
RL Sci. Rep. 5:13989-13989(2015).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27325672; DOI=10.1128/mcb.00156-16;
RA Bohovych I., Kastora S., Christianson S., Topil D., Kim H., Fangman T.,
RA Zhou Y.J., Barrientos A., Lee J., Brown A.J., Khalimonchuk O.;
RT "Oma1 links mitochondrial protein quality control and TOR signaling to
RT modulate physiological plasticity and cellular stress responses.";
RL Mol. Cell. Biol. 36:2300-2312(2016).
RN [11]
RP DISULFIDE BOND, SUBUNIT, AND MUTAGENESIS OF CYS-272 AND CYS-332.
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).
CC -!- FUNCTION: Protease that is part of the quality control system in the
CC inner membrane of mitochondria (PubMed:12963738, PubMed:22219186,
CC PubMed:24648523, PubMed:27325672). Activated in response to various
CC mitochondrial stress, leading to the proteolytic cleavage of target
CC proteins, such as OXA1 and COX1 (PubMed:12963738, PubMed:22219186,
CC PubMed:24648523). Cleaves and thereby promotes the turnover of
CC mistranslated or misfolded membrane proteins (PubMed:12963738,
CC PubMed:27325672). Cleaves the misfolded multi-pass membrane protein
CC OXA1 (PubMed:12963738). Involved in quality control of cytochrome
CC oxidase assembly: mediates the cleavage of COX1 in cells lacking COA2
CC (PubMed:22219186). Required for the stability of the respiratory
CC supercomplexes (PubMed:26365306). Required for TOR signaling
CC (PubMed:27325672). {ECO:0000269|PubMed:12963738,
CC ECO:0000269|PubMed:22219186, ECO:0000269|PubMed:24648523,
CC ECO:0000269|PubMed:26365306, ECO:0000269|PubMed:27325672}.
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 induced in response to
CC various mitochondrial stress, such as changes in membrane potential,
CC oxidative stress or chronic hyperpolarization, and depends on its C-
CC terminal region. {ECO:0000269|PubMed:24648523}.
CC -!- SUBUNIT: Homooligomer. {ECO:0000269|PubMed:24648523,
CC ECO:0000269|PubMed:31044600}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:12963738}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- PTM: Forms a redox-dependent disulfide bond, which plays a structural
CC role and regulates its conformational stability and activity.
CC {ECO:0000269|PubMed:31044600}.
CC -!- DISRUPTION PHENOTYPE: Reduced ability to form viable colonies on
CC glucose medium after acute treatment with hydrogen peroxide or chronic
CC exposure to carbonyl cyanide m-chlorophenylhydrazone (CCCP)
CC (PubMed:24648523). Cells are resistant to rapamycin and display reduced
CC TOR signaling (PubMed:27325672). Oxidative-stress response is impaired
CC (PubMed:27325672). {ECO:0000269|PubMed:24648523,
CC ECO:0000269|PubMed:27325672}.
CC -!- SIMILARITY: Belongs to the peptidase M48 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA81638.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA82166.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Z27116; CAA81638.1; ALT_FRAME; Genomic_DNA.
DR EMBL; Z28312; CAA82166.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BK006944; DAA09237.1; -; Genomic_DNA.
DR PIR; S38165; S38165.
DR RefSeq; NP_013013.2; NM_001179877.1.
DR AlphaFoldDB; P36163; -.
DR SMR; P36163; -.
DR BioGRID; 34218; 40.
DR DIP; DIP-5087N; -.
DR STRING; 4932.YKR087C; -.
DR MEROPS; M48.018; -.
DR MaxQB; P36163; -.
DR PaxDb; P36163; -.
DR PRIDE; P36163; -.
DR EnsemblFungi; YKR087C_mRNA; YKR087C; YKR087C.
DR GeneID; 853962; -.
DR KEGG; sce:YKR087C; -.
DR SGD; S000001795; OMA1.
DR VEuPathDB; FungiDB:YKR087C; -.
DR eggNOG; KOG2661; Eukaryota.
DR GeneTree; ENSGT00390000007027; -.
DR HOGENOM; CLU_029002_1_0_1; -.
DR InParanoid; P36163; -.
DR OMA; QANAFCL; -.
DR BioCyc; YEAST:G3O-32050-MON; -.
DR Reactome; R-SCE-169911; Regulation of Apoptosis.
DR PRO; PR:P36163; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36163; protein.
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:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0035694; P:mitochondrial protein catabolic process; IMP:UniProtKB.
DR GO; GO:0034982; P:mitochondrial protein processing; IBA:GO_Central.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; IMP:UniProtKB.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0051775; P:response to redox state; IMP:SGD.
DR GO; GO:0031929; P:TOR signaling; IMP:SGD.
DR InterPro; IPR001915; Peptidase_M48.
DR Pfam; PF01435; Peptidase_M48; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Mitochondrion; Mitochondrion inner membrane; Protease; Reference proteome;
KW Thioester bond; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..345
FT /note="Mitochondrial metalloendopeptidase OMA1"
FT /id="PRO_0000203225"
FT TOPO_DOM 1..67
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..345
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT REGION 314..345
FT /note="Required for protease activation"
FT /evidence="ECO:0000269|PubMed:24648523"
FT ACT_SITE 204
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:24648523"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT DISULFID 272..332
FT /evidence="ECO:0000269|PubMed:31044600"
FT MUTAGEN 203
FT /note="H->A: Significantly decreased protease activity."
FT /evidence="ECO:0000269|PubMed:24648523"
FT MUTAGEN 204
FT /note="E->A: Significantly decreased protease activity."
FT /evidence="ECO:0000269|PubMed:24648523"
FT MUTAGEN 204
FT /note="E->Q: Loss of protease activity."
FT /evidence="ECO:0000269|PubMed:12963738"
FT MUTAGEN 207
FT /note="H->Y: Loss of protease activity."
FT /evidence="ECO:0000269|PubMed:12963738"
FT MUTAGEN 212
FT /note="H->Y: Loss of protease activity."
FT /evidence="ECO:0000269|PubMed:12963738"
FT MUTAGEN 272
FT /note="C->A: Abolished disulfide bond, leading to impaired
FT conformational state; when associated with A-332."
FT /evidence="ECO:0000269|PubMed:31044600"
FT MUTAGEN 332
FT /note="C->A: Abolished disulfide bond, leading to impaired
FT conformational state; when associated with A-272."
FT /evidence="ECO:0000269|PubMed:31044600"
SQ SEQUENCE 345 AA; 39328 MW; 95B0EBCD25F435CF CRC64;
MLRNIIRFKG FGKGTSGGFL KPVSFRVQLT RCYRYDNGPS YRRFNNGEYS QKSSFKSILL
DKSSRKYLAL LFGGCSLFYY THLDKAPVSD RSRFIWVSRP LELTIGNYTY KSIWRQTQQE
ILPPQHPLSI KIENIFMKIV EAAYKDPSVD NSLLDGIKWE IHVVNDPTAS PNAFVLPGGK
VFIFSSILPI CANDDGIATV LAHEFAHQLA RHTAENLSKA PIYSLLGLVL YTVTGAHAIN
NILLDGFLRM PASRQMETEA DYIGLMIMSR ACFQPQESIK VWERMANFEK QMNRGGVVNM
EFLSTHPAST RRIENMSKWL PKANEIYEQS DCSSMGNYYK SFFSM
