OMA1_BOVIN
ID OMA1_BOVIN Reviewed; 523 AA.
AC Q3SZN3; F1N0Z4;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Metalloendopeptidase OMA1, mitochondrial {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q96E52};
DE AltName: Full=Overlapping with the m-AAA protease 1 homolog {ECO:0000250|UniProtKB:Q96E52};
DE Flags: Precursor;
GN Name=OMA1 {ECO:0000250|UniProtKB:Q96E52};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Metalloprotease that is part of the quality control system in
CC the inner membrane of mitochondria. Activated in response to various
CC mitochondrial stress, leading to the proteolytic cleavage of target
CC proteins, such as OPA1, UQCC3 and DELE1. Following stress conditions
CC that induce loss of mitochondrial membrane potential, mediates cleavage
CC of OPA1 at S1 position, leading to OPA1 inactivation and negative
CC regulation of mitochondrial fusion (By similarity). Also acts as a
CC regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage
CC of OPA1, leading to the remodeling of mitochondrial cristae and
CC allowing the release of cytochrome c from mitochondrial cristae. In
CC depolarized mitochondria, may also act as a backup protease for PINK1
CC by mediating PINK1 cleavage and promoting its subsequent degradation by
CC the proteasome. May also cleave UQCC3 in response to mitochondrial
CC depolarization. Also acts as an activator of the integrated stress
CC response (ISR): in response to mitochondrial stress, mediates cleavage
CC of DELE1 to generate the processed form of DELE1 (S-DELE1), which
CC translocates to the cytosol and activates EIF2AK1/HRI to trigger the
CC ISR (By similarity). Its role in mitochondrial quality control is
CC essential for regulating lipid metabolism as well as to maintain body
CC temperature and energy expenditure under cold-stress conditions. Binds
CC cardiolipin, possibly regulating its protein turnover. Required for the
CC stability of the respiratory supercomplexes (By similarity).
CC {ECO:0000250|UniProtKB:Q96E52, ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O75844};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O75844};
CC -!- ACTIVITY REGULATION: Protease activity is activated upon autocatalytic
CC cleavage in response to mitochondrial depolarization.
CC {ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- SUBUNIT: Homooligomer. {ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9D8H7}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- DOMAIN: The stress-sensor region regulates proteolysis and activation.
CC {ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- PTM: Autocatalytically cleaved in response to mitochondrial
CC depolarization both at the N-terminus and C-terminus to generate the
CC short active form (S-OMA1). Autocatalytic processing at the C-terminus
CC takes place at residues 447-456. The S-OMA1 form is unstable (By
CC similarity). Degradaded by YMEL1 in response to membrane depolarization
CC (By similarity). Protein turnover is regulated by prohibitin (PHB and
CC PHB2), which promotes degradation of OMA1 in a cardiolipin-binding
CC manner (By similarity). {ECO:0000250|UniProtKB:Q96E52,
CC ECO:0000250|UniProtKB:Q9D8H7}.
CC -!- PTM: May form a redox-dependent disulfide bond (By similarity). Exists
CC in a semi-oxidized state and is activated by prolonged hypoxia (By
CC similarity). {ECO:0000250|UniProtKB:P36163,
CC ECO:0000250|UniProtKB:Q96E52}.
CC -!- SIMILARITY: Belongs to the peptidase M48 family. {ECO:0000305}.
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DR EMBL; DAAA02008763; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC102774; AAI02775.1; -; mRNA.
DR RefSeq; NP_001030205.1; NM_001035033.2.
DR RefSeq; XP_005204593.1; XM_005204536.2.
DR AlphaFoldDB; Q3SZN3; -.
DR SMR; Q3SZN3; -.
DR STRING; 9913.ENSBTAP00000023044; -.
DR MEROPS; M48.017; -.
DR PaxDb; Q3SZN3; -.
DR PRIDE; Q3SZN3; -.
DR Ensembl; ENSBTAT00000023044; ENSBTAP00000023044; ENSBTAG00000017326.
DR GeneID; 506223; -.
DR KEGG; bta:506223; -.
DR CTD; 115209; -.
DR VEuPathDB; HostDB:ENSBTAG00000017326; -.
DR VGNC; VGNC:32428; OMA1.
DR eggNOG; KOG2661; Eukaryota.
DR GeneTree; ENSGT00390000007027; -.
DR HOGENOM; CLU_039633_0_0_1; -.
DR InParanoid; Q3SZN3; -.
DR OMA; ILGQWIQ; -.
DR OrthoDB; 960152at2759; -.
DR TreeFam; TF329133; -.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000017326; Expressed in oocyte and 105 other tissues.
DR ExpressionAtlas; Q3SZN3; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0140468; P:HRI-mediated signaling; ISS:UniProtKB.
DR GO; GO:0140467; P:integrated stress response signaling; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0034982; P:mitochondrial protein processing; ISS:UniProtKB.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; ISS:UniProtKB.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:1903850; P:regulation of cristae formation; ISS:UniProtKB.
DR GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR InterPro; IPR001915; Peptidase_M48.
DR Pfam; PF01435; Peptidase_M48; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Disulfide bond; Hydrolase; Lipid-binding; Membrane;
KW Metal-binding; Metalloprotease; Mitochondrion;
KW Mitochondrion inner membrane; Protease; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT TRANSIT 1..45
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT PROPEP 46..143
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT /id="PRO_0000450311"
FT CHAIN 144..?
FT /note="Metalloendopeptidase OMA1, mitochondrial"
FT /id="PRO_0000302808"
FT PROPEP ?..523
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT /id="PRO_0000450312"
FT TOPO_DOM 144..195
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..?
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT REGION 148..167
FT /note="Cardiolipin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT REGION 165..195
FT /note="Stress-sensor region"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT ACT_SITE 328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 327
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT DISULFID 407..465
FT /evidence="ECO:0000250|UniProtKB:P36163"
FT CONFLICT 477
FT /note="F -> L (in Ref. 2; AAI02775)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 59896 MW; A26E8867EE43A1A6 CRC64;
MSFIYGLQSA ARNCFFFRFN LLTNWRKCNT QAVTSRDFHQ VKINHIVNKS LGLGVNHGDR
WTPLPENFLF YRTFNTKRKG CLLSSRSKEI WMISRKCTAW TDSFSRQLPM KNVPVVPAHS
MSHPLNCLPT RDIRSFHTSP RCQAAPAPLL LMILKPAQKL LAIIVGRGIR KWWQALPPNK
KELFKESLRK NKWKLFLGLS SFGLLFVVFY FTHLEVSPVT GRSKLLILGK EHFRLLSELE
YEAWMEEFKN DMLTEKDARY VAVKAVVHHL IECNQDIPGI SEINWIIHVV DSPDINAFVL
PNGQVFVFTG LLNSVTDIHQ LSFLLGHEIA HAVLEHAAEK ASLVHLLDFL GLIFLTTIWA
ICPRDSLALL GQWIQSKLQE FLFDRPYSRT LEAEADRIGL QLAAKACVDV RASSVFWQQM
EFAESLHGHP KLPEWLSTHP SHGNRAEHLD RLIPQALKIR ETCNCPPLSG PDPRLLFKLS
MKNFLEAEKE DLNITVKQKM DALPIQNQKQ IPLTCIVDKR TGS
