OMA1_RAT
ID OMA1_RAT Reviewed; 504 AA.
AC D3ZS74;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Metalloendopeptidase OMA1, mitochondrial {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q96E52};
DE AltName: Full=Overlapping with the m-AAA protease 1 homolog {ECO:0000250|UniProtKB:Q96E52};
DE Flags: Precursor;
GN Name=Oma1 {ECO:0000312|RGD:1304821};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Metalloprotease that is part of the quality control system in
CC the inner membrane of mitochondria. Activated in response to various
CC mitochondrial stress, leading to the proteolytic cleavage of target
CC proteins, such as OPA1, UQCC3 and DELE1. Following stress conditions
CC that induce loss of mitochondrial membrane potential, mediates cleavage
CC of OPA1 at S1 position, leading to OPA1 inactivation and negative
CC regulation of mitochondrial fusion (By similarity). Also acts as a
CC regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage
CC of OPA1, leading to the remodeling of mitochondrial cristae and
CC allowing the release of cytochrome c from mitochondrial cristae. In
CC depolarized mitochondria, may also act as a backup protease for PINK1
CC by mediating PINK1 cleavage and promoting its subsequent degradation by
CC the proteasome. May also cleave UQCC3 in response to mitochondrial
CC depolarization. Also acts as an activator of the integrated stress
CC response (ISR): in response to mitochondrial stress, mediates cleavage
CC of DELE1 to generate the processed form of DELE1 (S-DELE1), which
CC translocates to the cytosol and activates EIF2AK1/HRI to trigger the
CC ISR (By similarity). Its role in mitochondrial quality control is
CC essential for regulating lipid metabolism as well as to maintain body
CC temperature and energy expenditure under cold-stress conditions. Binds
CC cardiolipin, possibly regulating its protein turnover. Required for the
CC stability of the respiratory supercomplexes (By similarity).
CC {ECO:0000250|UniProtKB:Q96E52, ECO:0000250|UniProtKB:Q9D8H7}.
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:0000250|UniProtKB:Q9D8H7}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- DOMAIN: The stress-sensor region regulates proteolysis and activation.
CC {ECO:0000250|UniProtKB:Q9D8H7}.
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). Autocatalytic processing at the C-terminus
CC takes place at residues 426-435. The S-OMA1 form is unstable (By
CC similarity). Degradaded by YMEL1 in response to membrane depolarization
CC (By similarity). Protein turnover is regulated by prohibitin (PHB and
CC PHB2), which promotes degradation of OMA1 in a cardiolipin-binding
CC manner (By similarity). {ECO:0000250|UniProtKB:Q96E52,
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 (By
CC similarity). {ECO:0000250|UniProtKB:P36163,
CC ECO:0000250|UniProtKB:Q96E52}.
CC -!- SIMILARITY: Belongs to the peptidase M48 family. {ECO:0000305}.
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DR EMBL; CH473998; EDL97870.1; -; Genomic_DNA.
DR RefSeq; NP_001100139.1; NM_001106669.1.
DR RefSeq; XP_006238537.1; XM_006238475.3.
DR AlphaFoldDB; D3ZS74; -.
DR SMR; D3ZS74; -.
DR STRING; 10116.ENSRNOP00000009515; -.
DR MEROPS; M48.017; -.
DR CarbonylDB; D3ZS74; -.
DR PaxDb; D3ZS74; -.
DR PeptideAtlas; D3ZS74; -.
DR GeneID; 298282; -.
DR KEGG; rno:298282; -.
DR UCSC; RGD:1304821; rat.
DR CTD; 115209; -.
DR RGD; 1304821; Oma1.
DR VEuPathDB; HostDB:ENSRNOG00000007214; -.
DR eggNOG; KOG2661; Eukaryota.
DR HOGENOM; CLU_039633_0_0_1; -.
DR InParanoid; D3ZS74; -.
DR OMA; ILGQWIQ; -.
DR OrthoDB; 960152at2759; -.
DR PhylomeDB; D3ZS74; -.
DR TreeFam; TF329133; -.
DR Reactome; R-RNO-169911; Regulation of Apoptosis.
DR PRO; PR:D3ZS74; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Proteomes; UP000234681; Chromosome 5.
DR Bgee; ENSRNOG00000007214; Expressed in quadriceps femoris and 18 other tissues.
DR Genevisible; D3ZS74; RN.
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; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0042407; P:cristae formation; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0140467; P:integrated stress response signaling; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0034982; P:mitochondrial protein processing; ISS:UniProtKB.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; ISS:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS: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; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:1903850; P:regulation of cristae formation; ISS:UniProtKB.
DR GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR InterPro; IPR001915; Peptidase_M48.
DR Pfam; PF01435; Peptidase_M48; 1.
PE 3: Inferred from homology;
KW Autocatalytic cleavage; Disulfide bond; Hydrolase; Lipid-binding; Membrane;
KW Metal-binding; Metalloprotease; Mitochondrion;
KW Mitochondrion inner membrane; Protease; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT TRANSIT 1..41
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT PROPEP 42..122
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT /id="PRO_0000450317"
FT CHAIN 123..?
FT /note="Metalloendopeptidase OMA1, mitochondrial"
FT /id="PRO_0000417519"
FT PROPEP ?..504
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT /id="PRO_0000450318"
FT TOPO_DOM 123..174
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..?
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT REGION 127..146
FT /note="Cardiolipin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT REGION 144..174
FT /note="Stress-sensor region"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT ACT_SITE 307
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT DISULFID 386..444
FT /evidence="ECO:0000250|UniProtKB:P36163"
SQ SEQUENCE 504 AA; 57145 MW; D7456DE65BC9ECDE CRC64;
MNFLYGLQSA TRNQFLSGVN TLARRRTWTP PAGCPLASRL PAVNANWGLS TVSHCYSVIL
LPRNLHFCRT LKNKRSRCLS SAQSKEMGVL TYNWTVWGDA SCSPNYAAIR EVRSFHTSAP
RQAAPVPLLM LILKPVQKLL AIIVGRGIRK WWQALPPDKK ALFKDSVKRN KWRLLLGLSA
FGLLFVVFYF THLEVSPVTG RSKLLLVGKE HFRLLSDLEY EVWMEEFKND LLPEEDPRYL
TVKKVVYHLT QCNQDVPGVS EINWVVHVVH SPKVNAFVLP NGQVFVFTGL LNSVTDMHQL
SFLLGHEIAH AVLGHAAEKA SLVHLLDFLG MIFLTMIWAI CPRDSLAVLG QWIQSKLQEY
MFDRPYSRTL EAEADKIGLQ LAAKACVDVR ASSVFWQQME FSESLHGYPK LPEWLSTHPS
HGNRAEYLDR LIPQALKLRE VCNCPPLSGP DPRLLFRLTV KHLLEDSEKE DLNITVKKQK
PDALPIQKQE QIPLTYALGK RTAG
