Opa1
entrez
74143
canonical
uniprot
P58281
canonical
ensembl
ENSMUSG00000038084
resolver
ensp
ENSMUSP00000036993
resolver
ensp
ENSMUSP00000123880
resolver
ensp
ENSMUSP00000124223
resolver
ensp
ENSMUSP00000246119
resolver
ensp
ENSMUSP00000246121
resolver
ensp
ENSMUSP00000246147
resolver
genesymbol
Opa1
resolver
uniprot
A6H6Q3
resolver
uniprot
H7BX01
resolver
uniprot
Q3ULA5
resolver
uniprot
Q8BKU7
resolver
uniprot
Q8BLL3
resolver
uniprot
Q8BM08
resolver
uniprot
Q8R3J7
resolver
uniprot_entry
OPA1_MOUSE
resolver
uniprot_sec
A6H6Q3
resolver
uniprot_sec
H7BX01
resolver
uniprot_sec
Q3ULA5
resolver
uniprot_sec
Q8BKU7
resolver
uniprot_sec
Q8BLL3
resolver
uniprot_sec
Q8BM08
resolver
uniprot_sec
Q8R3J7
resolver
activity_regulation
ACTIVITY REGULATION: Activated by guanine nucleotide exchange factor RCC1L. {ECO:0000250|UniProtKB:O60313}.
uniprot
proteins
amino_acid_sequence
MWRAGRAAVACEVCQSLVKHSSGIQRNVPLQKLHLVSRSIYRSHHPALKLQRPQLRTPFQQFSSLTHLSLHKLKLSPIKYGYQPRRNFWPARLAARLLKLRYIILGSAVGGGYTAKKTFDEWKDMIPDLSDYKWIVPDFIWEIDEYIDLEKIRKALPSSEDLASLAPDLDKITESLSLLKDFFTAGSPGETAFRATDHGSESDKHYRKVSDKEKIDQLQEELLHTQLKYQRILERLEKENKELRKLVLQKDDKGIHHRKLKKSLIDMYSEVLDVLSDYDASYNTQDHLPRVVVVGDQSAGKTSVLEMIAQARIFPRGSGEMMTRSPVKVTLSEGPHHVALFKDSSREFDLTKEEDLAALRHEIELRMRKNVKEGCTVSPETISLNVKGPGLQRMVLVDLPGVINTVTSGMAPDTKETIFSISKAYMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFVLTKVDLAEKNVASPSRIQQIIEGKLFPMKALGYFAVVTGKGNSSESIEAIREYEEEFFQNSKLLKTSMLKAHQVTTRNLSLAVSDCFWKMVRESVEQQADSFKATRFNLETEWKNNYPRLRELDRNELFEKAKNEILDEVISLSQVTPKHWEEILQQSLWERVSTHVIENIYLPAAQTMNSGTFNTTVDIKLKQWTDKQLPNKAVEVAWETLQEEFSRFMTEPKGKEHDDIFDKLKEAVKEESIKRHKWNDFAEDSLRVIQHNALEDRSISDKQQWDAAIYFMEEALQGRLKDTENAIENMIGPDWKKRWMYWKNRTQEQCVHNETKNELEKMLKVNDEHPAYLASDEITTVRKNLESRGVEVDPSLIKDTWHQVYRRHFLKTALNHCNLCRRGFYYYQRHFIDSELECNDVVLFWRIQRMLAITANTLRQQLTNTEVRRLEKNVKEVLEDFAEDGEKKVKLLTGKRVQLAEDLKKVREIQEKLDAFIEALHQEK
uniprot
proteins
ec_number
3.6.5.5
uniprot
proteins
function
FUNCTION: Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function (PubMed:11847212, PubMed:16839884, PubMed:16839885, PubMed:24055366, PubMed:24616225, PubMed:24627489, PubMed:25298396, PubMed:26785494, PubMed:28636943, PubMed:28746876, PubMed:33200421, PubMed:33237841, PubMed:36171294, PubMed:38225406). Exists in two forms: the transmembrane, long form (Dynamin-like GTPase OPA1, long form; L-OPA1), which is tethered to the inner mitochondrial membrane, and the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1), which results from proteolytic cleavage and localizes in the intermembrane space (PubMed:24703695, PubMed:28636943, PubMed:33237841). Both forms (L-OPA1 and S-OPA1) cooperate to catalyze the fusion of the mitochondrial inner membrane (PubMed:33237841). The equilibrium between L-OPA1 and S-OPA1 is essential: excess levels of S-OPA1, produced by cleavage by OMA1 following loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, inhibiting mitochondrial fusion (PubMed:33200421). The balance between L-OPA1 and S-OPA1 also influences cristae shape and morphology (PubMed:33200421, PubMed:38225406). Involved in remodeling cristae and the release of cytochrome c during apoptosis (PubMed:16839884). Proteolytic processing by PARL 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). Acts as a regulator of T-helper Th17 cells, which are characterized by cells with fused mitochondria with tight cristae, by mediating mitochondrial membrane remodeling: OPA1 is required for interleukin-17 (IL-17) production (PubMed:36171294). Its role in mitochondrial morphology is required for mitochondrial genome maintenance (By similarity). {ECO:0000250|UniProtKB:O60313, ECO:0000269|PubMed:11847212, ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:16839885, ECO:0000269|PubMed:24055366, ECO:0000269|PubMed:24616225, ECO:0000269|PubMed:24627489, ECO:0000269|PubMed:24703695, ECO:0000269|PubMed:25298396, ECO:0000269|PubMed:26785494, ECO:0000269|PubMed:28636943, ECO:0000269|PubMed:28746876, ECO:0000269|PubMed:33200421, ECO:0000269|PubMed:33237841, ECO:0000269|PubMed:36171294, ECO:0000269|PubMed:38225406}.; FUNCTION: [Dynamin-like GTPase OPA1, long form]: Constitutes the transmembrane long form (L-OPA1) that plays a central role in mitochondrial inner membrane fusion and cristae morphology (PubMed:20038678, PubMed:22433842, PubMed:25298396). L-OPA1 and the soluble short form (S-OPA1) form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes (By similarity). Inner membrane-anchored L-OPA1 molecules initiate membrane remodeling by recruiting soluble S-OPA1 to rapidly polymerize into a flexible cylindrical scaffold encaging the mitochondrial inner membrane (By similarity). Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature (By similarity). OPA1 dimerization through the paddle region, which inserts into cardiolipin-containing membrane, promotes GTP hydrolysis and the helical assembly of a flexible OPA1 lattice on the membrane, which drives membrane curvature and mitochondrial fusion (By similarity). Plays a role in the maintenance and remodeling of mitochondrial cristae, some invaginations of the mitochondrial inner membrane that provide an increase in the surface area (PubMed:16839884, PubMed:16839885, PubMed:25298396, PubMed:38225406). Probably acts by forming helical filaments at the inside of inner membrane tubes with the shape and dimensions of crista junctions (By similarity). The equilibrium between L-OPA1 and S-OPA1 influences cristae shape and morphology: increased L-OPA1 levels promote cristae stacking and elongated mitochondria, while increased S-OPA1 levels correlated with irregular cristae packing and round mitochondria shape (PubMed:38225406). {ECO:0000250|UniProtKB:G0SGC7, ECO:0000250|UniProtKB:O60313, ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:16839885, ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842, ECO:0000269|PubMed:25298396, ECO:0000269|PubMed:38225406}.; FUNCTION: [Dynamin-like GTPase OPA1, short form]: Constitutes the soluble short form (S-OPA1) generated by cleavage by OMA1, which plays a central role in mitochondrial inner membrane fusion and cristae morphology (PubMed:20038678, PubMed:22433842, PubMed:25298396). The transmembrane long form (L-OPA1) and the S-OPA1 form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes (By similarity). Inner membrane-anchored L-OPA1 molecules initiate membrane remodeling by recruiting soluble S-OPA1 to rapidly polymerize into a flexible cylindrical scaffold encaging the mitochondrial inner membrane (By similarity). Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature (By similarity). OPA1 dimerization through the paddle region, which inserts into cardiolipin-containing membrane, promotes GTP hydrolysis and the helical assembly of a flexible OPA1 lattice on the membrane, which drives membrane curvature and mitochondrial fusion (By similarity). Excess levels of S-OPA1 produced by cleavage by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, thereby inhibiting mitochondrial fusion (PubMed:20038678, PubMed:22433842). Involved in mitochondrial safeguard in response to transient mitochondrial membrane depolarization by mediating flickering: cleavage by OMA1 leads to excess production of S-OPA1, preventing mitochondrial hyperfusion (PubMed:24627489, PubMed:33200421). Plays a role in the maintenance and remodeling of mitochondrial cristae, some invaginations of the mitochondrial inner membrane that provide an increase in the surface area (PubMed:16839884, PubMed:16839885, PubMed:25298396, PubMed:38225406). Probably acts by forming helical filaments at the inside of inner membrane tubes with the shape and dimensions of crista junctions (By similarity). The equilibrium between L-OPA1 and S-OPA1 influences cristae shape and morphology: increased L-OPA1 levels promote cristae stacking and elongated mitochondria, while increased S-OPA1 levels correlated with irregular cristae packing and round mitochondria shape (PubMed:38225406). {ECO:0000250|UniProtKB:G0SGC7, ECO:0000250|UniProtKB:O60313, ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:16839885, ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842, ECO:0000269|PubMed:24627489, ECO:0000269|PubMed:25298396, ECO:0000269|PubMed:33200421, ECO:0000269|PubMed:38225406}.; FUNCTION: [Isoform 2]: Isoforms that contain the alternative exon 4b are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane. {ECO:0000250|UniProtKB:O60313}.
uniprot
proteins
mass_dalton
111339
uniprot
proteins
mutagenesis
MUTAGEN 285..960; /note="Missing: Knockin mice show embryonic lethality at 9 days post coitum (dpc)."; /evidence="ECO:0000269|PubMed:17428816"; MUTAGEN 297; /note="Q->V: Impaired ability to mediate mitochondrial inner membrane fusion without affecting cristae structures."; /evidence="ECO:0000269|PubMed:25298396"; MUTAGEN 300; /note="G->E: Abolished GTPase activity."; /evidence="ECO:0000269|PubMed:28636943
uniprot
proteins
post_translational_modification
PTM: Cleaved by OMA1 or YME1L1 downstream of the transmembrane region in response to different signals to generate soluble forms (PubMed:17003040, PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24616225, PubMed:24703695, PubMed:26785494, PubMed:28636943, PubMed:33200421, PubMed:33237841). Cleaved by OMA1 at position S1 following stress conditions, generating the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1) (PubMed:17003040, PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:33200421). AFG3L2 is involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:20038678). PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion (PubMed:16839884). {ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:17003040, ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842, ECO:0000269|PubMed:24550258, ECO:0000269|PubMed:24616225, ECO:0000269|PubMed:24703695, ECO:0000269|PubMed:26785494, ECO:0000269|PubMed:28636943, ECO:0000269|PubMed:33200421, ECO:0000269|PubMed:33237841}.; PTM: [Isoform 2]: Cleavage at position S2 by YME1L1 is required to mediate oxidative phosphorylation (OXPHOS)-induced mitochondrial fusion (PubMed:24616225, PubMed:24703695, PubMed:26785494). Cleavage occurs in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (By similarity). {ECO:0000250|UniProtKB:Q2TA68, ECO:0000269|PubMed:24616225, ECO:0000269|PubMed:24703695, ECO:0000269|PubMed:26785494}.; PTM: [Isoform 3]: Cleavage at position S3 by YME1L1 is required for membrane tubulation. {ECO:0000269|PubMed:33237841}.
uniprot
proteins
protein_family
Dynamin/Fzo/YdjA family
uniprot
proteins
protein_family
TRAFAC class dynamin-like GTPase superfamily
uniprot
proteins
pubmed
11847212
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16839884
uniprot
proteins
pubmed
16839885
uniprot
proteins
pubmed
17003040
uniprot
proteins
pubmed
17314202
uniprot
proteins
pubmed
17428816
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20038678
uniprot
proteins
pubmed
21081504
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22433842
uniprot
proteins
pubmed
24055366
uniprot
proteins
pubmed
24550258
uniprot
proteins
pubmed
24616225
uniprot
proteins
pubmed
24627489
uniprot
proteins
pubmed
24703695
uniprot
proteins
pubmed
25298396
uniprot
proteins
pubmed
26785494
uniprot
proteins
pubmed
28636943
uniprot
proteins
pubmed
28746876
uniprot
proteins
pubmed
33200421
uniprot
proteins
pubmed
33237841
uniprot
proteins
pubmed
36171294
uniprot
proteins
pubmed
38225406
uniprot
proteins
sequence_length
960
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Dynamin-like GTPase OPA1, long form]: Mitochondrion inner membrane {ECO:0000269|PubMed:11847212, ECO:0000269|PubMed:16839884, ECO:0000269|PubMed:21081504, ECO:0000269|PubMed:28746876}; Single-pass membrane protein {ECO:0000255}. Note=Detected at contact sites between endoplasmic reticulum and mitochondrion membranes. {ECO:0000250|UniProtKB:O60313}.; SUBCELLULAR LOCATION: [Dynamin-like GTPase OPA1, short form]: Mitochondrion intermembrane space {ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22433842}.
uniprot
proteins
transmembrane_region
TRANSMEM 97..113; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins