| IED ID | IndEnz0002010577 |
| Enzyme Type ID | protease010577 |
| Protein Name |
Metalloendopeptidase OMA1, mitochondrial EC 3.4.24.- Overlapping with the m-AAA protease 1 homolog |
| Gene Name | Oma1 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MSLLYGLQSTRINRFLSGVNNLANRRQWTPPASCPLAPKLRAVNAYWGLNTVSHCHSVTLLPRNFLFCRTLNHKKSRCLSSAQSKELGVLTYRCTVRGDSVLRQGARKVAGVPALAASCSPSCPAVIEARSFRTSARVQAAPVPLLLLILKPVQKLLAIIVGRGIRKWWQALPPNKKELFKDSVRKNKWRLLLGLSAFGLLFVVFYFTHLEVSPVTGRSKLLLVGKEHFRLLSDLEYEVWMEEFKNDLLPERDPRYLTVKEMVYHLTQCNRDVPGISETNWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGHAAEKASLVHLLDFLGMIFLTMIWAICPRDSLAVLGQWIQSKLQEYMFDRPYSRTLEAEADKVGLQLAAKACADVRASSVFWQQMEFSESLHGYPKLPEWLSTHPSHGNRAEYLDRLIPQALKLREVCNCPPLSGPDPRLLFRLTVKRFLEDSEKEDLNITVKKQKTDALPMQKQEQIPLTYVLEKRTAG |
| Enzyme Length | 521 |
| Uniprot Accession Number | Q9D8H7 |
| Absorption | |
| Active Site | ACT_SITE 324; /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, ECO:0000305|PubMed:24550258, ECO:0000305|PubMed:24719224" |
| Activity Regulation | ACTIVITY REGULATION: Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization. {ECO:0000269|PubMed:24550258, ECO:0000269|PubMed:24719224}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.24.- |
| Enzyme Function | FUNCTION: Metalloprotease that is part of the quality control system in the inner membrane of mitochondria (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24719224, PubMed:24616225, PubMed:26785494). Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24616225, PubMed:26785494). Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24616225, PubMed:26785494, PubMed:26783299). Also acts as a regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage of OPA1, leading to the remodeling of mitochondrial cristae and allowing the release of cytochrome c from mitochondrial cristae (By similarity). In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome (By similarity). May also cleave UQCC3 in response to mitochondrial depolarization (By similarity). Also acts as an activator of the integrated stress response (ISR): in response to mitochondrial stress, mediates cleavage of DELE1 to generate the processed form of DELE1 (S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR (By similarity). Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions (PubMed:22433842). Binds cardiolipin, possibly regulating its protein turnover (PubMed:31819158). Required for the stability of the respiratory supercomplexes (PubMed:26365306). {ECO:0000250|UniProtKB:Q96E52, ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842, ECO:0000269|PubMed:24550258, ECO:0000269|PubMed:24616225, ECO:0000269|PubMed:24719224, ECO:0000269|PubMed:26365306, ECO:0000269|PubMed:26783299, ECO:0000269|PubMed:26785494, ECO:0000269|PubMed:31819158}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (2); Chain (1); Disulfide bond (1); Metal binding (3); Mutagenesis (1); Propeptide (2); Region (2); Sequence conflict (1); Topological domain (2); Transit peptide (1); Transmembrane (1) |
| Keywords | Alternative splicing;Autocatalytic cleavage;Direct protein sequencing;Disulfide bond;Hydrolase;Lipid-binding;Membrane;Metal-binding;Metalloprotease;Mitochondrion;Mitochondrion inner membrane;Protease;Reference proteome;Transit peptide;Transmembrane;Transmembrane helix;Zinc;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:24550258, ECO:0000305|PubMed:20038678}; Single-pass membrane protein {ECO:0000305|PubMed:24550258}. |
| Modified Residue | |
| Post Translational Modification | PTM: Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1) (PubMed:24550258, PubMed:24719224). Autocatalytic processing at the C-terminus takes place at residues 443-452 (PubMed:24719224). The S-OMA1 form is unstable (PubMed:24719224). Degradaded by YMEL1 in response to membrane depolarization (By similarity). Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner (PubMed:31819158). {ECO:0000250|UniProtKB:Q96E52, ECO:0000269|PubMed:24550258, ECO:0000269|PubMed:24719224, ECO:0000269|PubMed:31819158}.; PTM: May form a redox-dependent disulfide bond (By similarity). Exists in a semi-oxidized state and is activated by prolonged hypoxia (By similarity). {ECO:0000250|UniProtKB:P36163, ECO:0000250|UniProtKB:Q96E52}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11217851; 12446734; 12466851; 16284245; 18614015; 21267068; 21677750; 24671334; 24681487; 27642048; 29688375; 30389680; 32338760; |
| Motif | |
| Gene Encoded By | |
| Mass | 58,878 |
| Kinetics | |
| Metal Binding | METAL 323; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 327; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 388; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095 |
| Rhea ID | |
| Cross Reference Brenda |