UniProtKB/Swiss-Prot P00395: Variant p.Gly125Asp

Cytochrome c oxidase subunit 1
Gene: MT-CO1
Chromosomal location: M
Variant information

Variant position:  125
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glycine (G) to Aspartate (D) at position 125 (G125D, p.Gly125Asp).
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 glycine (G) to medium size and acidic (D)
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

Involvement in disease:  Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:16407113}. Note=The gene represented in this entry may be involved in disease pathogenesis.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CRC; displays steady-state catalytic activity linked to proton pumping that is approximately 34% of wild-type; an intrinsic proton leak is find in the enzyme, which will lead to decreased overall energy-conversion efficiency of the respiratory chain, perturbing transport processes such as protein, ion and metabolite trafficking.
Any additional useful information about the variant.



Sequence information

Variant position:  125
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  513
The length of the canonical sequence.

Location on the sequence:   LPPSLLLLLASAMVEAGAGT  G WTVYPPLAGNYSHPGASVDL
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                         LPPSLLLLLASAMVEAGAGTGWTVYPPLAGNYSHPGASVDL

                              LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Chimpanzee                    LPPSLLLLLASAMVEAGAGTGWTVYPPLAGNYSHPGASVDL

Mouse                         LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Rat                           LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Pig                           LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Bovine                        LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Rabbit                        LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Sheep                         LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Cat                           LPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDL

Horse                         LPPSFLLLLASSMIEAGAGTGWTVYPPLAGNLAHAGASVDL

Chicken                       LPPSFLLLLASSTVEAGAGTGWTVYPPLAGNLAHAGASVDL

Xenopus laevis                LPPSFLLLLASSGVEAGAGTGWTVYPPLAGNLAHAGASVDL

Zebrafish                     LPPSFLLLLASSGVEAGAGTGWTVYPPLAGNLAHAGASVDL

Caenorhabditis elegans        LPTSMLLILDACFVDMGCGTSWTVYPPLSTM-GHPGSSVDL

Drosophila                    LPPALSLLLVSSMVENGAGTGWTVYPPLSAGIAHGGASVDL

Slime mold                    IIVSFFLLLTSSCVGIGVGTGWTVYPPLSTMEYHPGHAVDV

Baker's yeast                 LPMGLVCLVTSTLVESGAGTGWTVYPPLSSIQAHSGPSVDL

Fission yeast                 LPPALMLLLISALTEEGPGGGWTVYPPLSSITSHSGPAIDL

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.

TypePositionsDescription
Chain 1 – 513 Cytochrome c oxidase subunit 1
Topological domain 123 – 146 Mitochondrial intermembrane


Literature citations

Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.
Greaves L.C.; Preston S.L.; Tadrous P.J.; Taylor R.W.; Barron M.J.; Oukrif D.; Leedham S.J.; Deheragoda M.; Sasieni P.; Novelli M.R.; Jankowski J.A.Z.; Turnbull D.M.; Wright N.A.; McDonald S.A.C.;
Proc. Natl. Acad. Sci. U.S.A. 103:714-719(2006)
Cited for: VARIANTS CRC ASP-125 AND PRO-458;

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.
Namslauer I.; Brzezinski P.;
Proc. Natl. Acad. Sci. U.S.A. 106:3402-3407(2009)
Cited for: CHARACTERIZATION OF VARIANTS CRC ASP-125 AND PRO-458;

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.