Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P54098: Variant p.Tyr955Cys

DNA polymerase subunit gamma-1
Gene: POLG
Feedback?
Variant information Variant position: help 955 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Tyrosine (Y) to Cysteine (C) at position 955 (Y955C, p.Tyr955Cys). 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: help Change from large size and aromatic (Y) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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: help In PEOA1, PEOB1 and SANDO; 45-fold decrease in apparent binding affinity for the incoming nucleoside triphosphate; 2-fold less accurate for basepair substitutions than wild-type. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 955 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1239 The length of the canonical sequence.
Location on the sequence: help TATTVGISREHAKIFNYGRI Y GAGQPFAERLLMQFNHRLTQ 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TATTVGISREHAKIFNYGRIYGAGQPFAERLLMQFNHRLTQ

Mouse                         TAATVGISREHAKIFNYGRIYGAGQSFAERLLMQFNHRLTR

Rat                           TAATVGISREHAKVFNYGRIYGAGQSFAERLLMQFNHRLSR

Xenopus laevis                TASTVGISREHAKVFNYGRIYGAGQPFAERLLMQFNHRLTQ

Drosophila                    TAKAVGISRDHAKVINYARIYGAGQLFAETLLRQFNPTFSA
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 1239 DNA polymerase subunit gamma-1
Motif 943 – 958 Pol B
Binding site 943 – 943
Binding site 947 – 947
Binding site 951 – 951



Literature citations
Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions.
Van Goethem G.; Dermaut B.; Loefgren A.; Martin J.-J.; Van Broeckhoven C.;
Nat. Genet. 28:211-212(2001)
Cited for: VARIANTS PEOB1 PRO-3; ARG-304; THR-467 AND CYS-955; Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia.
Lamantea E.; Tiranti V.; Bordoni A.; Toscano A.; Bono F.; Servidei S.; Papadimitriou A.; Spelbrink H.; Silvestri L.; Casari G.; Comi G.P.; Zeviani M.;
Ann. Neurol. 52:211-219(2002)
Cited for: VARIANTS PEOA1 ASP-923; HIS-943; CYS-955; SER-957 AND LEU-1176; VARIANTS PEOB1 ILE-251; LEU-309 AND SER-848; Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis.
Ponamarev M.V.; Longley M.J.; Nguyen D.; Kunkel T.A.; Copeland W.C.;
J. Biol. Chem. 277:15225-15228(2002)
Cited for: CHARACTERIZATION OF VARIANT PEOA1 CYS-955; FUNCTION; CATALYTIC ACTIVITY; Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.
Van Goethem G.; Martin J.-J.; Dermaut B.; Loefgren A.; Wibail A.; Ververken D.; Tack P.; Dehaene I.; Van Zandijcke M.; Moonen M.; Ceuterick C.; De Jonghe P.; Van Broeckhoven C.;
Neuromuscul. Disord. 13:133-142(2003)
Cited for: VARIANTS SANDO PRO-3; ARG-304; THR-467; TRP-627 AND CYS-955; Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study.
Luoma P.; Melberg A.; Rinne J.O.; Kaukonen J.A.; Nupponen N.N.; Chalmers R.M.; Oldfors A.; Rautakorpi I.; Peltonen L.; Majamaa K.; Somer H.; Suomalainen A.;
Lancet 364:875-882(2004)
Cited for: VARIANTS PEOA1 CYS-953 AND CYS-955; VARIANTS PEOB1 ASP-468 AND THR-1105;
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.