UniProtKB - Q96E52 (OMA1_HUMAN)
Metalloendopeptidase OMA1, mitochondrial
OMA1
Functioni
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).
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:20038677, PubMed:25275009).
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).
By similarity6 PublicationsCaution
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 327 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 328 | PROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 331 | Zinc; catalyticBy similarity | 1 | |
Metal bindingi | 392 | Zinc; catalyticPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- lipid binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- metalloendopeptidase activity Source: UniProtKB
GO - Biological processi
- cristae formation Source: Ensembl
- diet induced thermogenesis Source: UniProtKB
- energy homeostasis Source: UniProtKB
- glucose metabolic process Source: UniProtKB
- HRI-mediated signaling Source: UniProtKB
- integrated stress response signaling Source: UniProtKB
- lipid metabolic process Source: UniProtKB
- mitochondrial protein processing Source: UniProtKB
- mitochondrial respiratory chain complex assembly Source: UniProtKB
- negative regulation of mitochondrial fusion Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- protein autoprocessing Source: UniProtKB
- protein quality control for misfolded or incompletely synthesized proteins Source: UniProtKB
- proteolysis involved in cellular protein catabolic process Source: GO_Central
- regulation of apoptotic process Source: Reactome
- regulation of cristae formation Source: UniProtKB
- zymogen activation Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Ligand | Lipid-binding, Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q96E52 |
Reactomei | R-HSA-169911, Regulation of Apoptosis |
SignaLinki | Q96E52 |
Protein family/group databases
MEROPSi | M48.017 |
TCDBi | 8.A.150.1.1, the mitochondrial metalloendopeptidase oma1 (oma1) family |
Names & Taxonomyi
Protein namesi | Recommended name: Metalloendopeptidase OMA1, mitochondrialCurated (EC:3.4.24.-3 Publications)Alternative name(s): Metalloprotease-related protein 11 Publication Short name: MPRP-11 Publication Overlapping with the m-AAA protease 1 homolog1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:29661, OMA1 |
neXtProti | NX_Q96E52 |
VEuPathDBi | HostDB:ENSG00000162600 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 1 Publication1 Publication; Single-pass membrane protein By similarity
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrial membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 144 – 195 | Mitochondrial matrixBy similarityAdd BLAST | 52 | |
Transmembranei | 196 – 216 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 217 – ? | Mitochondrial intermembraneBy similarity |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 328 | 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. 2 Publications | 1 | |
Mutagenesisi | 331 | H → A: Abolishes ability to cleave OPA1 at S1 position. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 115209 |
OpenTargetsi | ENSG00000162600 |
PharmGKBi | PA134911478 |
Miscellaneous databases
Pharosi | Q96E52, Tbio |
Genetic variation databases
BioMutai | OMA1 |
DMDMi | 74751828 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 13 | MitochondrionSequence analysisAdd BLAST | 13 | |
PropeptideiPRO_0000450313 | 14 – 143 | By similarityAdd BLAST | 130 | |
ChainiPRO_0000302809 | 144 – ? | Metalloendopeptidase OMA1, mitochondrial | ||
PropeptideiPRO_0000450314 | ? – 524 | By similarity |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 407 ↔ 465 | By similarity |
Post-translational modificationi
Keywords - PTMi
Autocatalytic cleavage, Disulfide bond, ZymogenProteomic databases
EPDi | Q96E52 |
jPOSTi | Q96E52 |
MassIVEi | Q96E52 |
MaxQBi | Q96E52 |
PaxDbi | Q96E52 |
PeptideAtlasi | Q96E52 |
PRIDEi | Q96E52 |
ProteomicsDBi | 76375 [Q96E52-1] 76376 [Q96E52-2] |
PTM databases
iPTMneti | Q96E52 |
PhosphoSitePlusi | Q96E52 |
SwissPalmi | Q96E52 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000162600, Expressed in corpus callosum and 209 other tissues |
ExpressionAtlasi | Q96E52, baseline and differential |
Genevisiblei | Q96E52, HS |
Organism-specific databases
HPAi | ENSG00000162600, Low tissue specificity |
Interactioni
Subunit structurei
Homooligomer.
By similarityProtein-protein interaction databases
BioGRIDi | 125420, 135 interactors |
IntActi | Q96E52, 103 interactors |
STRINGi | 9606.ENSP00000360270 |
Miscellaneous databases
RNActi | Q96E52, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 148 – 167 | Cardiolipin-bindingBy similarityAdd BLAST | 20 | |
Regioni | 165 – 195 | Stress-sensor regionBy similarityAdd BLAST | 31 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transit peptide, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2661, Eukaryota |
GeneTreei | ENSGT00390000007027 |
HOGENOMi | CLU_039633_0_0_1 |
InParanoidi | Q96E52 |
OMAi | IVFYFTH |
OrthoDBi | 960152at2759 |
PhylomeDBi | Q96E52 |
TreeFami | TF329133 |
Family and domain databases
InterProi | View protein in InterPro IPR001915, Peptidase_M48 |
Pfami | View protein in Pfam PF01435, Peptidase_M48, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSFICGLQSA ARNHVFFRFN SLSNWRKCNT LASTSRGCHQ VQVNHIVNKY
60 70 80 90 100
QGLGVNQCDR WSFLPGNFHF YSTFNNKRTG GLSSTKSKEI WRITSKCTVW
110 120 130 140 150
NDAFSRQLLI KEVTAVPSLS VLHPLSPASI RAIRNFHTSP RFQAAPVPLL
160 170 180 190 200
LMILKPVQKL FAIIVGRGIR KWWQALPPNK KEVVKENIRK NKWKLFLGLS
210 220 230 240 250
SFGLLFVVFY FTHLEVSPIT GRSKLLLLGK EQFRLLSELE YEAWMEEFKN
260 270 280 290 300
DMLTEKDARY LAVKEVLCHL IECNKDVPGI SQINWVIHVV DSPIINAFVL
310 320 330 340 350
PNGQMFVFTG FLNSVTDIHQ LSFLLGHEIA HAVLGHAAEK AGMVHLLDFL
360 370 380 390 400
GMIFLTMIWA ICPRDSLALL CQWIQSKLQE YMFNRPYSRK LEAEADKIGL
410 420 430 440 450
LLAAKACADI RASSVFWQQM EFVDSLHGQP KMPEWLSTHP SHGNRVEYLD
460 470 480 490 500
RLIPQALKIR EMCNCPPLSN PDPRLLFKLS TKHFLEESEK EDLNITKKQK
510 520
MDTLPIQKQE QIPLTYIVEK RTGS
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7BZX2 | H7BZX2_HUMAN | Metalloendopeptidase OMA1, mitochon... | OMA1 | 328 | Annotation score: | ||
X6RDQ1 | X6RDQ1_HUMAN | Metalloendopeptidase OMA1, mitochon... | OMA1 | 325 | Annotation score: | ||
X6RIG5 | X6RIG5_HUMAN | Metalloendopeptidase OMA1, mitochon... | OMA1 | 255 | Annotation score: | ||
X6RL62 | X6RL62_HUMAN | Metalloendopeptidase OMA1, mitochon... | OMA1 | 252 | Annotation score: | ||
S4R3A3 | S4R3A3_HUMAN | Metalloendopeptidase OMA1, mitochon... | OMA1 | 87 | Annotation score: | ||
X6RD49 | X6RD49_HUMAN | Metalloendopeptidase OMA1, mitochon... | OMA1 | 183 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034958 | 67 | N → K. Corresponds to variant dbSNP:rs34466938EnsemblClinVar. | 1 | |
Natural variantiVAR_065755 | 69 | H → Y in a patient with amyotrophic lateral sclerosis. 1 PublicationCorresponds to variant dbSNP:rs75220198EnsemblClinVar. | 1 | |
Natural variantiVAR_034959 | 117 | P → L1 PublicationCorresponds to variant dbSNP:rs17117720Ensembl. | 1 | |
Natural variantiVAR_034960 | 211 | F → C. Corresponds to variant dbSNP:rs17117699Ensembl. | 1 | |
Natural variantiVAR_035708 | 226 | L → V in a colorectal cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_065756 | 272 | E → G in a patient with amyotrophic lateral sclerosis. 1 PublicationCorresponds to variant dbSNP:rs139938730Ensembl. | 1 | |
Natural variantiVAR_034961 | 329 | I → L1 PublicationCorresponds to variant dbSNP:rs17117678Ensembl. | 1 | |
Natural variantiVAR_065757 | 365 | D → Y1 PublicationCorresponds to variant dbSNP:rs77980955EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_027958 | 456 – 524 | ALKIR…KRTGS → LVREEKFIEQPEQIAELTLN SFIQNTEICRS in isoform 2. 1 PublicationAdd BLAST | 69 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB048348 mRNA Translation: BAC79381.1 AL109845 Genomic DNA No translation available. AL365187 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06631.1 CH471059 Genomic DNA Translation: EAX06632.1 CH471059 Genomic DNA Translation: EAX06633.1 BC012915 mRNA Translation: AAH12915.1 AK091101 mRNA Translation: BAC03583.1 Different initiation. |
CCDSi | CCDS608.1 [Q96E52-1] |
RefSeqi | NP_660286.1, NM_145243.4 [Q96E52-1] |
Genome annotation databases
Ensembli | ENST00000371226; ENSP00000360270; ENSG00000162600 |
GeneIDi | 115209 |
KEGGi | hsa:115209 |
MANE-Selecti | ENST00000371226.8; ENSP00000360270.3; NM_145243.5; NP_660286.1 |
UCSCi | uc001cyy.4, human [Q96E52-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB048348 mRNA Translation: BAC79381.1 AL109845 Genomic DNA No translation available. AL365187 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06631.1 CH471059 Genomic DNA Translation: EAX06632.1 CH471059 Genomic DNA Translation: EAX06633.1 BC012915 mRNA Translation: AAH12915.1 AK091101 mRNA Translation: BAC03583.1 Different initiation. |
CCDSi | CCDS608.1 [Q96E52-1] |
RefSeqi | NP_660286.1, NM_145243.4 [Q96E52-1] |
3D structure databases
SMRi | Q96E52 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 125420, 135 interactors |
IntActi | Q96E52, 103 interactors |
STRINGi | 9606.ENSP00000360270 |
Protein family/group databases
MEROPSi | M48.017 |
TCDBi | 8.A.150.1.1, the mitochondrial metalloendopeptidase oma1 (oma1) family |
PTM databases
iPTMneti | Q96E52 |
PhosphoSitePlusi | Q96E52 |
SwissPalmi | Q96E52 |
Genetic variation databases
BioMutai | OMA1 |
DMDMi | 74751828 |
Proteomic databases
EPDi | Q96E52 |
jPOSTi | Q96E52 |
MassIVEi | Q96E52 |
MaxQBi | Q96E52 |
PaxDbi | Q96E52 |
PeptideAtlasi | Q96E52 |
PRIDEi | Q96E52 |
ProteomicsDBi | 76375 [Q96E52-1] 76376 [Q96E52-2] |
Protocols and materials databases
Antibodypediai | 46900, 93 antibodies from 25 providers |
DNASUi | 115209 |
Genome annotation databases
Ensembli | ENST00000371226; ENSP00000360270; ENSG00000162600 |
GeneIDi | 115209 |
KEGGi | hsa:115209 |
MANE-Selecti | ENST00000371226.8; ENSP00000360270.3; NM_145243.5; NP_660286.1 |
UCSCi | uc001cyy.4, human [Q96E52-1] |
Organism-specific databases
CTDi | 115209 |
DisGeNETi | 115209 |
GeneCardsi | OMA1 |
HGNCi | HGNC:29661, OMA1 |
HPAi | ENSG00000162600, Low tissue specificity |
neXtProti | NX_Q96E52 |
OpenTargetsi | ENSG00000162600 |
PharmGKBi | PA134911478 |
VEuPathDBi | HostDB:ENSG00000162600 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2661, Eukaryota |
GeneTreei | ENSGT00390000007027 |
HOGENOMi | CLU_039633_0_0_1 |
InParanoidi | Q96E52 |
OMAi | IVFYFTH |
OrthoDBi | 960152at2759 |
PhylomeDBi | Q96E52 |
TreeFami | TF329133 |
Enzyme and pathway databases
PathwayCommonsi | Q96E52 |
Reactomei | R-HSA-169911, Regulation of Apoptosis |
SignaLinki | Q96E52 |
Miscellaneous databases
BioGRID-ORCSi | 115209, 8 hits in 1048 CRISPR screens |
ChiTaRSi | OMA1, human |
GenomeRNAii | 115209 |
Pharosi | Q96E52, Tbio |
PROi | PR:Q96E52 |
RNActi | Q96E52, protein |
Gene expression databases
Bgeei | ENSG00000162600, Expressed in corpus callosum and 209 other tissues |
ExpressionAtlasi | Q96E52, baseline and differential |
Genevisiblei | Q96E52, HS |
Family and domain databases
InterProi | View protein in InterPro IPR001915, Peptidase_M48 |
Pfami | View protein in Pfam PF01435, Peptidase_M48, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | OMA1_HUMAN | |
Accessioni | Q96E52Primary (citable) accession number: Q96E52 Secondary accession number(s): D3DQ54 Q8NBB3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 11, 2007 |
Last sequence update: | December 1, 2001 | |
Last modified: | February 23, 2022 | |
This is version 157 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - SIMILARITY comments
Index of protein domains and families