OMA1
entrez
115209
canonical
uniprot
Q96E52
canonical
ensembl
ENSG00000162600
resolver
ensp
ENSP00000360270
resolver
genesymbol
OMA1
resolver
genesymbol_syn
MPRP1
resolver
hgnc
HGNC:29661
resolver
uniprot
D3DQ54
resolver
uniprot
Q5T3G6
resolver
uniprot
Q5T3G7
resolver
uniprot
Q5T3G8
resolver
uniprot
Q5T3G9
resolver
uniprot
Q5T3H0
resolver
uniprot
Q8NBB3
resolver
uniprot_entry
OMA1_HUMAN
resolver
uniprot_sec
D3DQ54
resolver
uniprot_sec
Q5T3G6
resolver
uniprot_sec
Q5T3G7
resolver
uniprot_sec
Q5T3G8
resolver
uniprot_sec
Q5T3G9
resolver
uniprot_sec
Q5T3H0
resolver
uniprot_sec
Q8NBB3
resolver
activity_regulation
ACTIVITY REGULATION: Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization. {ECO:0000250|UniProtKB:Q9D8H7}.
uniprot
proteins
amino_acid_sequence
MSFICGLQSAARNHVFFRFNSLSNWRKCNTLASTSRGCHQVQVNHIVNKYQGLGVNQCDRWSFLPGNFHFYSTFNNKRTGGLSSTKSKEIWRITSKCTVWNDAFSRQLLIKEVTAVPSLSVLHPLSPASIRAIRNFHTSPRFQAAPVPLLLMILKPVQKLFAIIVGRGIRKWWQALPPNKKEVVKENIRKNKWKLFLGLSSFGLLFVVFYFTHLEVSPITGRSKLLLLGKEQFRLLSELEYEAWMEEFKNDMLTEKDARYLAVKEVLCHLIECNKDVPGISQINWVIHVVDSPIINAFVLPNGQMFVFTGFLNSVTDIHQLSFLLGHEIAHAVLGHAAEKAGMVHLLDFLGMIFLTMIWAICPRDSLALLCQWIQSKLQEYMFNRPYSRKLEAEADKIGLLLAAKACADIRASSVFWQQMEFVDSLHGQPKMPEWLSTHPSHGNRVEYLDRLIPQALKIREMCNCPPLSNPDPRLLFKLSTKHFLEESEKEDLNITKKQKMDTLPIQKQEQIPLTYIVEKRTGS
uniprot
proteins
ec_number
3.4.24.-
uniprot
proteins
function
FUNCTION: Metalloprotease that is part of the quality control system in the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, PubMed:32132706, PubMed:32132707). Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, PubMed:25275009, PubMed:32132706, PubMed:32132707). 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:31922487). 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:20038677, PubMed:25275009). 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 (By similarity). 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 (PubMed:25275009). In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial depolarization (PubMed:25605331). 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 (PubMed:32132706, PubMed:32132707). 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 (By similarity). Binds cardiolipin, possibly regulating its protein turnover (By similarity). Required for the stability of the respiratory supercomplexes (By similarity). {ECO:0000250|UniProtKB:Q9D8H7, ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009, ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118, ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}.
uniprot
proteins
mass_dalton
60120
uniprot
proteins
mutagenesis
MUTAGEN 328; /note="E->Q: Abolished protease activity and ability to mediate cleavage of DELE1 in response to mitochondrial stress. Abolished ability to mediate cleavage of PINK1 in depolarized mitochondria."; /evidence="ECO:0000269|PubMed:30733118, ECO:0000269|PubMed:32132706"; MUTAGEN 331; /note="H->A: Abolishes ability to cleave OPA1 at S1 position."; /evidence="ECO:0000269|PubMed:20038677
uniprot
proteins
post_translational_modification
PTM: May form a redox-dependent disulfide bond (By similarity). Exists in a semi-oxidized state and is activated by prolonged hypoxia (PubMed:31044600). {ECO:0000250|UniProtKB:P36163, ECO:0000269|PubMed:31044600}.; PTM: Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1) (By similarity). Autocatalytic processing at the C-terminus takes place at residues 447-456 (By similarity). The S-OMA1 form is unstable (By similarity). OMA1 pre-processing by AFG3L2 may participate in maturation before OMA1 autocatalytic cleavage (PubMed:29545505). Degraded by YMEL1 in response to membrane depolarization (PubMed:26923599). Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner (By similarity). {ECO:0000250|UniProtKB:Q9D8H7, ECO:0000269|PubMed:26923599, ECO:0000269|PubMed:29545505}.
uniprot
proteins
protein_family
Peptidase M48 family
uniprot
proteins
pubmed
12886954
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
20038677
uniprot
proteins
pubmed
21220648
uniprot
proteins
pubmed
25275009
uniprot
proteins
pubmed
25605331
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26923599
uniprot
proteins
pubmed
29545505
uniprot
proteins
pubmed
30733118
uniprot
proteins
pubmed
31044600
uniprot
proteins
pubmed
31922487
uniprot
proteins
pubmed
32132706
uniprot
proteins
pubmed
32132707
uniprot
proteins
sequence_length
524
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:32132707, ECO:0000305|PubMed:20038677}; Single-pass membrane protein {ECO:0000250|UniProtKB:Q9D8H7}.
uniprot
proteins
transmembrane_region
TRANSMEM 196..216; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins