OMA1_DANRE
ID OMA1_DANRE Reviewed; 478 AA.
AC E9QBI7;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Metalloendopeptidase OMA1, mitochondrial {ECO:0000305};
DE Short=zfoma1 {ECO:0000303|PubMed:26365306};
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:0000303|PubMed:26365306};
GN ORFNames=si:ch73-215a11.1 {ECO:0000303|PubMed:23594743};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26365306; DOI=10.1038/srep13989;
RA Bohovych I., Fernandez M.R., Rahn J.J., Stackley K.D., Bestman J.E.,
RA Anandhan A., Franco R., Claypool S.M., Lewis R.E., Chan S.S.,
RA Khalimonchuk O.;
RT "metalloprotease OMA1 fine-tunes mitochondrial bioenergetic function and
RT respiratory supercomplex stability.";
RL Sci. Rep. 5:13989-13989(2015).
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 and dele1. Following stress conditions that
CC induce loss of mitochondrial membrane potential, mediates cleavage of
CC opa1 at S1 position, leading to opa1 inactivation and negative
CC regulation of mitochondrial fusion (By similarity). Also acts as an
CC activator of the integrated stress response (ISR): in response to
CC mitochondrial stress, mediates cleavage of dele1 to generate the
CC processed form of dele1 (S-DELE1), which translocates to the cytosol
CC and activates eif2ak1/hri to trigger the ISR (By similarity). Required
CC for the stability of the respiratory supercomplexes (PubMed:26365306).
CC {ECO:0000250|UniProtKB:Q96E52, ECO:0000250|UniProtKB:Q9D8H7,
CC ECO:0000269|PubMed:26365306}.
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). The S-OMA1 form is unstable.
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 -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes
CC developmental defects, such as pericardial edema, smaller eyes and
CC shorter body length (PubMed:26365306). Bioenergetics defects are
CC observed in dells (PubMed:26365306). {ECO:0000269|PubMed:26365306}.
CC -!- SIMILARITY: Belongs to the peptidase M48 family. {ECO:0000305}.
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DR EMBL; CU856363; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E9QBI7; -.
DR STRING; 7955.ENSDARP00000119103; -.
DR PaxDb; E9QBI7; -.
DR ZFIN; ZDB-GENE-091204-124; oma1.
DR eggNOG; KOG2661; Eukaryota.
DR InParanoid; E9QBI7; -.
DR PRO; PR:E9QBI7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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: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; IMP: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.
PE 3: Inferred from homology;
KW Autocatalytic cleavage; Disulfide bond; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Mitochondrion; Mitochondrion inner membrane; Protease;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix;
KW Zinc; Zymogen.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT PROPEP ?..111
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT /id="PRO_0000450319"
FT CHAIN 112..?
FT /note="Metalloendopeptidase OMA1, mitochondrial"
FT /id="PRO_0000417520"
FT PROPEP ?..478
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT /id="PRO_0000450320"
FT TOPO_DOM ?..162
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..?
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT REGION 134..164
FT /note="Stress-sensor region"
FT /evidence="ECO:0000250|UniProtKB:Q9D8H7"
FT ACT_SITE 297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 361
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT DISULFID 376..434
FT /evidence="ECO:0000250|UniProtKB:P36163"
SQ SEQUENCE 478 AA; 54050 MW; 7FE406BD2CBFB963 CRC64;
MQQTCIRLVK LDMLSTLTRF RTHSAIRCCA QRLFHCRPSL FISARTYFIK IDSSSLPKLK
GSVSFSASCV SLGSSRLGLC SSSFKTGAPA ALRAPVVFQR TRGFHTSGRR RALPALPLLW
MVLKPLQKIM AIILGRSIRK WWVALPANKK QLFREWSWRR RWHFLGAGTG LLFIASLFFF
THLDESPITG RTRLLVFSRK NFRELAQFNA DAFMEEFKDS LIASSDPRHK VVEQVVQILA
QRNQDIAEIS AVPWTVHVVD SPTMNAFVLP NGEIFVFTGM LNAVTDIHQL TFILGHEMAH
ALIGHAAEQA SLSHVVELLS LVLLTAIWAV CPRDSLAALG HWIQGKLVQF LFDRPFSRKL
EAEADQVGLQ MAAKACADVR AGPVFWEQME IFDQLSGQPT MPEWLSTHPS HQNRVRQLDR
LIPEALELRA RCNCPELPKT DPRVVFNEAV RLVLEGKKEQ MLEKEEKNGK TQTGDMFP
