| IED ID | IndEnz0002008339 |
| Enzyme Type ID | protease008339 |
| Protein Name |
Dynamin-like 120 kDa protein, mitochondrial EC 3.6.5.5 Large GTP-binding protein LargeG Optic atrophy protein 1 homolog Cleaved into: Dynamin-like 120 kDa protein, form S1 |
| Gene Name | Opa1 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MWRAGRAAVACEVCQSLVKHSSGIQRNVPLQKLHLVSRSIYRSHHPALKLQRPQLRTPFQQFSSLTHLSLHKLKLSPIKYGYQPRRNFWPARLAARLLKLRYIILGSAVGGGYTAKKTFDEWKDMIPDLSDYKWIVPDFIWEIDEYIDLEKIRKALPSSEDLASLAPDLDKITESLSLLKDFFTAGSPGETAFRATDHGSESDKHYRKVSDKEKIDQLQEELLHTQLKYQRILERLEKENKELRKLVLQKDDKGIHHRKLKKSLIDMYSEVLDVLSDYDASYNTQDHLPRVVVVGDQSAGKTSVLEMIAQARIFPRGSGEMMTRSPVKVTLSEGPHHVALFKDSSREFDLTKEEDLAALRHEIELRMRKNVKEGCTVSPETISLNVKGPGLQRMVLVDLPGVINTVTSGMAPDTKETIFSISKAYMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFVLTKVDLAEKNVASPSRIQQIIEGKLFPMKALGYFAVVTGKGNSSESIEAIREYEEEFFQNSKLLKTSMLKAHQVTTRNLSLAVSDCFWKMVRESVEQQADSFKATRFNLETEWKNNYPRLRELDRNELFEKAKNEILDEVISLSQVTPKHWEEILQQSLWERVSTHVIENIYLPAAQTMNSGTFNTTVDIKLKQWTDKQLPNKAVEVAWETLQEEFSRFMTEPKGKEHDDIFDKLKEAVKEESIKRHKWNDFAEDSLRVIQHNALEDRSISDKQQWDAAIYFMEEALQGRLKDTENAIENMIGPDWKKRWMYWKNRTQEQCVHNETKNELEKMLKVNDEHPAYLASDEITTVRKNLESRGVEVDPSLIKDTWHQVYRRHFLKTALNHCNLCRRGFYYYQRHFIDSELECNDVVLFWRIQRMLAITANTLRQQLTNTEVRRLEKNVKEVLEDFAEDGEKKVKLLTGKRVQLAEDLKKVREIQEKLDAFIEALHQEK |
| Enzyme Length | 960 |
| Uniprot Accession Number | P58281 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Activated by guanine nucleotide exchange factor RCC1L. {ECO:0000250|UniProtKB:O60313}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.5; Evidence={ECO:0000250|UniProtKB:O60313}; |
| DNA Binding | |
| EC Number | 3.6.5.5 |
| Enzyme Function | FUNCTION: Dynamin-related GTPase that is essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission (PubMed:11847212, PubMed:24616225, PubMed:26785494, PubMed:28746876). Coexpression of isoform 1 with shorter alternative products is required for optimal activity in promoting mitochondrial fusion (By similarity). Binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation. The intrinsic GTPase activity is low, and is strongly increased by interaction with lipid membranes (By similarity). Plays a role in remodeling cristae and the release of cytochrome c during apoptosis (PubMed:16839884, PubMed:16839885). Proteolytic processing in response to intrinsic apoptotic signals may lead to disassembly of OPA1 oligomers and release of the caspase activator cytochrome C (CYCS) into the mitochondrial intermembrane space (PubMed:16839884, PubMed:16839885). Plays a role in mitochondrial genome maintenance (By similarity). {ECO:0000250|UniProtKB:O60313, ECO:0000269|PubMed:11847212, ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:16839885, ECO:0000269|PubMed:24616225, ECO:0000269|PubMed:26785494, ECO:0000269|PubMed:28746876}.; FUNCTION: [Dynamin-like 120 kDa protein, form S1]: Produced by cleavage at position S1 by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion. {ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842}.; FUNCTION: Isoforms that contain the alternative exon 4b (present in isoform 2, but not in isoform 1) are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane. {ECO:0000250|UniProtKB:O60313}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 295..302; /note=GTP; /evidence=ECO:0000255; NP_BIND 398..402; /note=GTP; /evidence=ECO:0000255; NP_BIND 467..470; /note=GTP; /evidence=ECO:0000255 |
| Features | Alternative sequence (1); Chain (2); Coiled coil (2); Domain (1); Erroneous initiation (1); Modified residue (1); Motif (1); Nucleotide binding (3); Region (5); Sequence conflict (2); Site (1); Topological domain (2); Transit peptide (1); Transmembrane (1) |
| Keywords | Acetylation;Alternative splicing;Apoptosis;Coiled coil;GTP-binding;Hydrolase;Lipid-binding;Membrane;Mitochondrion;Mitochondrion inner membrane;Nucleotide-binding;Reference proteome;Sensory transduction;Transit peptide;Transmembrane;Transmembrane helix;Vision |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:21081504, ECO:0000269|PubMed:28746876}; Single-pass membrane protein {ECO:0000255}. Mitochondrion {ECO:0000269|PubMed:11847212}. Mitochondrion membrane {ECO:0000250|UniProtKB:O60313}. Note=Detected at contact sites between endoplasmic reticulum and mitochondrion membranes. {ECO:0000250|UniProtKB:O60313}. |
| Modified Residue | MOD_RES 228; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:O60313 |
| Post Translational Modification | PTM: PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion (PubMed:20038678, PubMed:24550258, PubMed:22433842). Cleaved by OMA1 at position S1 following stress conditions (PubMed:20038678, PubMed:24550258, PubMed:22433842). {ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842, ECO:0000269|PubMed:24550258}.; PTM: [Isoform 2]: Cleavage at position S2 is mediated by YME1L (PubMed:24616225, PubMed:26785494). Cleavage may occur in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (By similarity). {ECO:0000250|UniProtKB:Q2TA68, ECO:0000269|PubMed:24616225, ECO:0000269|PubMed:26785494}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11217851; 12466851; 12520002; 12735796; 12865426; 14610273; 14651853; 15161824; 15505078; 15509649; 15755804; 15899901; 16075367; 16267818; 16602821; 16615898; 16635246; 17003040; 17035996; 17314202; 17428816; 18200046; 18419770; 18469184; 18614015; 18691924; 19234344; 19360003; 19443720; 19477917; 19578372; 19609448; 19815013; 19834041; 20064504; 20185555; 20450306; 20652258; 20664796; 20817698; 21041314; 21346246; 21551073; 21642619; 21677750; 21803037; 21983901; 22158479; 22300878; 22406748; 22482729; 22579715; 22658590; 22858546; 22902477; 23250881; 23316298; 23409176; 23453807; 23509143; 23714779; 23906536; 24042504; 24043775; 24055366; 24282027; 24344202; 24627489; 24671334; 24686499; 24703695; 25298396; 25352671; 25387754; 25393477; 25531304; 26024391; 26039448; 26039449; 26218912; 26375863; 26393574; 26472072; 26783299; 26820596; 27166947; 27260406; 27468686; 27587279; 27723783; 27861891; 27974214; 27997827; 28159969; 28188211; 28552492; 28591639; 28607005; 28636943; 28637784; 28890359; 29320742; 29632021; 30017357; 30068998; 30143614; 30333037; 31189900; 31199663; 31208084; 31269804; 31281574; 31337982; 31502361; 31551424; 31574344; 31883840; 32202296; 32245890; 32289155; 32315597; 32571921; 32756920; 33231680; 33237841; 33664336; 33944779; 34048907; 34072974; 34133045; 34343501; 34360957; 34669477; |
| Motif | MOTIF P58281-2:217..222; /note=LQQQIQ motif; /evidence=ECO:0000250|UniProtKB:Q2TA68 |
| Gene Encoded By | |
| Mass | 111,339 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:19669 |
| Cross Reference Brenda | 3.6.5.5; |