Q9D8H7 · OMA1_MOUSE
- ProteinMetalloendopeptidase OMA1, mitochondrial
- GeneOma1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids521 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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:26785494, PubMed:26783299).
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).
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:26785494, PubMed:26783299).
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
Note: Binds 1 zinc ion per subunit.
Activity regulation
Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMetalloendopeptidase OMA1, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9D8H7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Single-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 140-191 | Mitochondrial matrix | ||||
Sequence: AAPVPLLLLILKPVQKLLAIIVGRGIRKWWQALPPNKKELFKDSVRKNKWRL | ||||||
Transmembrane | 192-212 | Helical | ||||
Sequence: LLGLSAFGLLFVVFYFTHLEV | ||||||
Topological domain | 213-? | Mitochondrial intermembrane | ||||
Sequence: MSLLYGLQSTRINRFLSGVNNLANRRQWTPPASCPLAPKLRAVNAYWGLNTVSHCHSVTLLPRNFLFCRTLNHKKSRCLSSAQSKELGVLTYRCTVRGDSVLRQGARKVAGVPALAASCSPSCPAVIEARSFRTSARVQAAPVPLLLLILKPVQKLLAIIVGRGIRKWWQALPPNKKELFKDSVRKNKWRLLLGLSAFGLLFVVFYFTHLEV |
Keywords
- Cellular component
Phenotypes & Variants
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).
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).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 324 | Abolished protease activity and ability to cleave OPA1. Abolished autocatalytic processing. | ||||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 30 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for propeptide, transit peptide, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Propeptide | PRO_0000450316 | ?-521 | ||||
Sequence: MSLLYGLQSTRINRFLSGVNNLANRRQWTPPASCPLAPKLRAVNAYWGLNTVSHCHSVTLLPRNFLFCRTLNHKKSRCLSSAQSKELGVLTYRCTVRGDSVLRQGARKVAGVPALAASCSPSCPAVIEARSFRTSARVQAAPVPLLLLILKPVQKLLAIIVGRGIRKWWQALPPNKKELFKDSVRKNKWRLLLGLSAFGLLFVVFYFTHLEVSPVTGRSKLLLVGKEHFRLLSDLEYEVWMEEFKNDLLPERDPRYLTVKEMVYHLTQCNRDVPGISETNWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGHAAEKASLVHLLDFLGMIFLTMIWAICPRDSLAVLGQWIQSKLQEYMFDRPYSRTLEAEADKVGLQLAAKACADVRASSVFWQQMEFSESLHGYPKLPEWLSTHPSHGNRAEYLDRLIPQALKLREVCNCPPLSGPDPRLLFRLTVKRFLEDSEKEDLNITVKKQKTDALPMQKQEQIPLTYVLEKRTAG | ||||||
Transit peptide | 1-79 | Mitochondrion | ||||
Sequence: MSLLYGLQSTRINRFLSGVNNLANRRQWTPPASCPLAPKLRAVNAYWGLNTVSHCHSVTLLPRNFLFCRTLNHKKSRCL | ||||||
Propeptide | PRO_0000450315 | 80-139 | ||||
Sequence: SSAQSKELGVLTYRCTVRGDSVLRQGARKVAGVPALAASCSPSCPAVIEARSFRTSARVQ | ||||||
Chain | PRO_0000302810 | 140-? | Metalloendopeptidase OMA1, mitochondrial | |||
Sequence: MSLLYGLQSTRINRFLSGVNNLANRRQWTPPASCPLAPKLRAVNAYWGLNTVSHCHSVTLLPRNFLFCRTLNHKKSRCLSSAQSKELGVLTYRCTVRGDSVLRQGARKVAGVPALAASCSPSCPAVIEARSFRTSARVQ | ||||||
Disulfide bond | 403↔461 | |||||
Sequence: CADVRASSVFWQQMEFSESLHGYPKLPEWLSTHPSHGNRAEYLDRLIPQALKLREVCNC |
Post-translational modification
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).
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).
May form a redox-dependent disulfide bond (By similarity).
Exists in a semi-oxidized state and is activated by prolonged hypoxia (By similarity).
Exists in a semi-oxidized state and is activated by prolonged hypoxia (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 144-163 | Cardiolipin-binding | ||||
Sequence: PLLLLILKPVQKLLAIIVGR | ||||||
Region | 161-191 | Stress-sensor region | ||||
Sequence: VGRGIRKWWQALPPNKKELFKDSVRKNKWRL |
Domain
The stress-sensor region regulates proteolysis and activation.
Sequence similarities
Belongs to the peptidase M48 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q9D8H7-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length521
- Mass (Da)58,878
- Last updated2001-06-01 v1
- Checksum80BCBFA70C9E2D5F
Q9D8H7-2
- Name2
Features
Showing features for sequence conflict, alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK008020 EMBL· GenBank· DDBJ | BAB25414.1 EMBL· GenBank· DDBJ | mRNA | ||
AK076209 EMBL· GenBank· DDBJ | BAC36255.1 EMBL· GenBank· DDBJ | mRNA | ||
AK136208 EMBL· GenBank· DDBJ | BAE22875.1 EMBL· GenBank· DDBJ | mRNA | ||
AL772338 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC016238 EMBL· GenBank· DDBJ | AAH16238.1 EMBL· GenBank· DDBJ | mRNA |