UniProtKB/Swiss-Prot O60313 : Variant p.Ser545Arg
Dynamin-like GTPase OPA1, mitochondrial
Gene: OPA1
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Variant information
Variant position:
545
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
The variants are classified into three categories: LP/P, LB/B and US.LP/P: likely pathogenic or pathogenic. LB/B: likely benign or benign. US: uncertain significance
Residue change:
From Serine (S) to Arginine (R) at position 545 (S545R, p.Ser545Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:
Change from small size and polar (S) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
-1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another: Lowest score: -4 (low probability of substitution).Highest score: 11 (high probability of substitution). More information can be found on the following page
Variant description:
In DOA+ and OPA1; decreased GTPase activity; loss of function in promoting mitochondrial fusion.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
545
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
960
The length of the canonical sequence.
Location on the sequence:
NSKLLKTSMLKAHQVTTRNL
S LAVSDCFWKMVRESVEQQAD
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:
The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human NSKLLKTSMLKAHQVTTRNLS LAVSDCFWKMVRESVEQQAD
Mouse NSKLLKTSMLKAHQVTTRNLS LAVSDCFWKMVRESVEQQAD
Rat NSKLLKTSMLKAHQVTTRNLS LAVSDCFWKMVRESVEQQAD
Chicken NSKLLKTSMLKAHQVTTKNLS LAVSDCFWKMVRESVEQQAD
Zebrafish NSRLLKDGMLKAHQVTTKNLS LAVSDCFWKMVRESVEQQAD
Sequence annotation in neighborhood:
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:Type: the type of sequence feature. Positions: endpoints of the sequence feature. Description: contains additional information about the feature.
Type Positions Description
Chain
88 – 960
Dynamin-like GTPase OPA1, long form
Chain
195 – 960
Dynamin-like GTPase OPA1, short form
Topological domain
114 – 770
Mitochondrial intermembrane
Domain
285 – 561
Dynamin-type G
Mutagenesis
557 – 557
R -> A. In interface mutant 9; strongly decreased ability to mediate mitochondrial fusion; when associated with A-213, A-217 and A-565.
Mutagenesis
565 – 565
D -> A. In interface mutant 9; strongly decreased ability to mediate mitochondrial fusion; when associated with A-213, A-217 and A-557.
Helix
541 – 559
Literature citations
OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation.
Ban T.; Heymann J.A.; Song Z.; Hinshaw J.E.; Chan D.C.;
Hum. Mol. Genet. 19:2113-2122(2010)
Cited for: FUNCTION; CATALYTIC ACTIVITY; DOMAIN; SUBUNIT; CHARACTERIZATION OF VARIANTS OPA1 GLU-300; VAL-439; HIS-445; ARG-545; LYS-728; ARG-785 AND PRO-939; CHARACTERIZATION OF VARIANTS VARIANT DOA+ THR-357; VAL-439; HIS-445; ARG-545 AND ASP-910;
Novel mutations in the OPA1 gene and associated clinical features in Japanese patients with optic atrophy.
Nakamura M.; Lin J.; Ueno S.; Asaoka R.; Hirai T.; Hotta Y.; Miyake Y.; Terasaki H.;
Ophthalmology 113:483-488(2006)
Cited for: VARIANT OPA1 ARG-545;
Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance.
Hudson G.; Amati-Bonneau P.; Blakely E.L.; Stewart J.D.; He L.; Schaefer A.M.; Griffiths P.G.; Ahlqvist K.; Suomalainen A.; Reynier P.; McFarland R.; Turnbull D.M.; Chinnery P.F.; Taylor R.W.;
Brain 131:329-337(2008)
Cited for: VARIANT DOA+ ARG-545;
OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes.
Amati-Bonneau P.; Valentino M.L.; Reynier P.; Gallardo M.E.; Bornstein B.; Boissiere A.; Campos Y.; Rivera H.; de la Aleja J.G.; Carroccia R.; Iommarini L.; Labauge P.; Figarella-Branger D.; Marcorelles P.; Furby A.; Beauvais K.; Letournel F.; Liguori R.; La Morgia C.; Montagna P.; Liguori M.; Zanna C.; Rugolo M.; Cossarizza A.; Wissinger B.; Verny C.; Schwarzenbacher R.; Martin M.A.; Arenas J.; Ayuso C.; Garesse R.; Lenaers G.; Bonneau D.; Carelli V.;
Brain 131:338-351(2008)
Cited for: VARIANTS DOA+ THR-357; VAL-439; HIS-445; ARG-545 AND ASP-910; FUNCTION;
Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations.
Ferre M.; Bonneau D.; Milea D.; Chevrollier A.; Verny C.; Dollfus H.; Ayuso C.; Defoort S.; Vignal C.; Zanlonghi X.; Charlin J.-F.; Kaplan J.; Odent S.; Hamel C.P.; Procaccio V.; Reynier P.; Amati-Bonneau P.;
Hum. Mutat. 30:E692-E705(2009)
Cited for: VARIANTS OPA1 MET-95; CYS-102; 293-VAL-VAL-294 DEL; ARG-310; THR-357; MET-382; PRO-396; 429-PRO-ASN-430 DEL; ASP-430; ARG-449; PHE-ILE-PHE-463 INS; LYS-487; ARG-545; TYR-551; GLN-590; PRO-593; LEU-646; ASP-768; TRP-781; TYR-823; LEU-882; PRO-887; CYS-932 AND PRO-949;
Disclaimer:
Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.