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UniProtKB/Swiss-Prot P00395: Variant p.Ser458Pro

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

Variant position:  458
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Serine (S) to Proline (P) at position 458 (S458P, p.Ser458Pro).
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 medium size and hydrophobic (P)
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, ECO:0000269|PubMed:19218458}. 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; the mutant is probably not expressed, indicating that the amino acid substitution results in a severely altered overall structure of the enzyme.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  458
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:   RRYSDYPDAYTTWNILSSVG  S FISLTAVMLMIFMIWEAFAS
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                         RRYSDYPDAYTTWNILSSVGSFISLTAVMLMIF--------------------------------------------------------------------MIW-----------------EAFAS

                              RRYSDYPDAYTTWNTVSSMGSFISLTAVMLMIF--------

Chimpanzee                    RRYSDYPDAYTTWNVLSSVGSFISLTAVMLMIF--------

Mouse                         RRYSDYPDAYTTWNTVSSMGSFISLTAVLIMIF--------

Rat                           RRYSDYPDAYTTWNTVSSMGSFISLTAVLVMIF--------

Pig                           RRYSDYPDAYTAWNTISSMGSFISLTAVMLMIF--------

Bovine                        RRYSDYPDAYTMWNTISSMGSFISLTAVMLMVF--------

Rabbit                        RRYSDYPDAYTMWNTVSSMGSFISLTAVMVMIF--------

Goat                          RRYSDYPDAYTMWNTISSMGSFISLTAVMLMIF--------

Sheep                         RRYSDYPDAYTMWNTISSMGSFISLTAVMLMIF--------

Cat                           RRYSDYPDAYTTWNTISSMGSFISLTAVMLMVF--------

Horse                         RRYSDYPDAYTTWNTISSMGSFISLTAVMLMIF--------

Chicken                       RRYSDYPDAYTLWNTLSSIGSLISMTAVIMLMF--------

Xenopus laevis                RRYSDYPDAYTLWNTVSSIGSLISLVAVIMMMF--------

Zebrafish                     RRYSDYPDAYALWNTVSSIGSLISLVAVIMFLF--------

Caenorhabditis elegans        RKYLDYPDVYSVWNIIASYGSIISTAGLFLFIY--------

Drosophila                    RRYSDYPDAYTTWNIVSTIGSTISLLGILFFFF--------

Slime mold                    RRIGDYPDAYIGWNLIASYGSLITAFGLLFFVVNIFTPYIR

Baker's yeast                 RRIPDYPDAFAGWNYVASIGSFIATLSLFLFIY--------

Fission yeast                 RRIPDYPEAFVGWNFVSSIGSVISILSLFLFMY--------

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
Transmembrane 451 – 473 Helical; Name=12


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.