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Details on Person UniProt:Q9D8H7 Oma1
| Class:Id | ReferenceGeneProduct:241072 |
|---|---|
| _chainChangeLog | transit peptide:1-79 added on Fri February 6 2015;chain:80-521 added on Fri February 6 2015;chain:80-521 for 241072 removed on Wed August 26 2020;propeptide:80-139 for 241072 added on Wed August 26 2020;chain:140- for 241072 added on Wed August 26 2020;propeptide:-521 for 241072 added on Wed August 26 2020 |
| _displayName | UniProt:Q9D8H7 Oma1 |
| _timestamp | 2025-02-21 20:12:27 |
| chain | transit peptide:1-79 propeptide:80-139 chain:140- propeptide:-521 |
| checksum | 80BCBFA70C9E2D5F |
| comment | FUNCTION Metalloprotease that is part of the quality control system in the inner membrane of mitochondria (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24616225, PubMed:24719224, 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). Involved in the fusion of the mitochondrial inner membranes by mediating cleavage of OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which cooperates with the membrane form (L-OPA1) to coordinate the fusion of mitochondrial inner membranes (PubMed:20038678, PubMed:24616225). Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1, leading to excess production of soluble OPA1 (S-OPA1) and negative regulation of mitochondrial fusion (PubMed:22433842, PubMed:24550258, PubMed:26783299, PubMed:26785494). Involved in mitochondrial safeguard in response to transient mitochondrial membrane depolarization (flickering) by catalyzing cleavage of OPA1, leading to excess production of S-OPA1, preventing mitochondrial hyperfusion (PubMed:33200421). 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).COFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization.SUBUNIT Homooligomer.SUBCELLULAR LOCATION The stress-sensor region regulates proteolysis and activation.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). OMA1 pre-processing by AFG3L2 may participate in maturation before OMA1 autocatalytic cleavage (By similarity). Degraded 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).PTM May form a redox-dependent disulfide bond (By similarity). Exists in a semi-oxidized state and is activated by prolonged hypoxia (By similarity).DISRUPTION PHENOTYPE Mice develop normally with males and females being fertile (PubMed:22433842). They however display transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters (PubMed:22433842). Moreover, mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis (PubMed:22433842). Mice are protected against heart failure by averting cardiomyocyte death in different murine heart failure models (PubMed:29593106). Mice with a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 have normal cardiac function and do not display myocardial fibrosis, contrary to mice with a single, cardiomyocyte-specific disruption of Yme1l (PubMed:26785494). Likewise, cardiomyocyte mitochondria have normal morphology (PubMed:26785494). Mice with a skeletal muscle Yme1l gene disruption plus a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 display normal glucose tolerance (PubMed:26785494).SIMILARITY Belongs to the peptidase M48 family. |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: fullName evidence="19"Metalloendopeptidase OMA1, mitochondrial ecNumber evidence="6 8 10"3.4.24.- alternativeName: fullName evidence="18"Overlapping with the m-AAA protease 1 homolog |
| geneName | Oma1 |
| identifier | Q9D8H7 |
| isSequenceChanged | FALSE |
| keyword | 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 |
| modified | [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | Oma1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | OMA1_MOUSE Q3UWN9 |
| sequenceLength | 521 |
| species | [Species:48892] Mus musculus |
| (isoformParent) | [ReferenceIsoform:241073] UniProt:Q9D8H7-2 Oma1 [Mus musculus] [ReferenceIsoform:413891] UniProt:Q9D8H7-1 Oma1 [Mus musculus] |
| (referenceEntity) | [EntityWithAccessionedSequence:9840531] Oma1(140-443) [mitochondrial inner membrane] [Mus musculus] [EntityWithAccessionedSequence:9840533] Oma1(140-521) [mitochondrial inner membrane] [Mus musculus] |
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No pathways have been reviewed or authored by UniProt:Q9D8H7 Oma1 (241072)
