UniProtKB/Swiss-Prot Q9H078 : Variant p.Thr268Met
Mitochondrial disaggregase
Gene: CLPB
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Variant information
Variant position:
268
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 Threonine (T) to Methionine (M) at position 268 (T268M, p.Thr268Met).
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 medium size and polar (T) to medium size and hydrophobic (M)
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 MGCA7B; increased ATP hydrolysis activity; severely decreased ATP-dependent protein disaggregase activity.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
268
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
707
The length of the canonical sequence.
Location on the sequence:
ITREDDFNNRLNNRASFKGC
T ALHYAVLADDYRTVKELLDG
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 ITREDDFNNRLNNRASFKGCT ALHYAVLADDYRTVKELLDG
Mouse VTREDDFNNRLNHRASFKGCT ALHYAVLADDYSIVKELLDR
Rat VTREDDFNNRLNHRASFKGCT ALHYAVLADDYSIVKELLGG
Bovine VTREDDFNNRLNNRASFKGCT ALHYAVLADDYRTVKELLDG
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
37 – 707
Mitochondrial disaggregase
Chain
127 – 707
Mitochondrial disaggregase, cleaved form
Repeat
265 – 295
ANK 3
Mutagenesis
257 – 257
R -> E. Shows higher order assembly but disaggregase activity is severely impaired by 70-80%.
Literature citations
Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations.
Cupo R.R.; Shorter J.;
Elife 9:0-0(2020)
Cited for: FUNCTION; DOMAIN; REGION; MUTAGENESIS OF LYS-387; TYR-430; GLU-455; ARG-475 AND ARG-650; CHARACTERIZATION OF VARIANTS MGCA7B MET-268 AND VAL-591;
CLPB variants associated with autosomal-recessive mitochondrial disorder with cataract, neutropenia, epilepsy, and methylglutaconic aciduria.
Saunders C.; Smith L.; Wibrand F.; Ravn K.; Bross P.; Thiffault I.; Christensen M.; Atherton A.; Farrow E.; Miller N.; Kingsmore S.F.; Ostergaard E.;
Am. J. Hum. Genet. 96:258-265(2015)
Cited for: VARIANT MGCA7B MET-268; TISSUE SPECIFICITY;
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.