Home  |  Contact

UniProtKB/Swiss-Prot P00395: Variant p.Ile280Thr

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

Variant position:  280
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Isoleucine (I) to Threonine (T) at position 280 (I280T, p.Ile280Thr).
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 hydrophobic (I) to medium size and polar (T)
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:  Note=MT-CO1 may play a role in the pathogenesis of acquired idiopathic sideroblastic anemia, a disease characterized by inadequate formation of heme and excessive accumulation of iron in mitochondria. Mitochondrial iron overload may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. {ECO:0000269|PubMed:9389715, ECO:0000269|PubMed:9851701}.
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:  Found in two patients with acquired idiopathic sideroblastic anemia.
Any additional useful information about the variant.

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



Sequence information

Variant position:  280
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:   YYSGKKEPFGYMGMVWAMMS  I GFLGFIVWAHHMFTVGMDVD
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                         YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

                              YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Chimpanzee                    YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Mouse                         YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGLDVD

Rat                           YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGLDVD

Pig                           YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Bovine                        YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Rabbit                        YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Goat                          YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Sheep                         YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Cat                           YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Horse                         YYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD

Chicken                       YYAGKKEPFGYMGMVWAMLSIGFLGFIVWAHHMFTVRMDVD

Xenopus laevis                YYSGKKEPFGYMGMVWAMMSIGLLGFIVWAHHMFTVDLNVD

Zebrafish                     YYAGKKEPFGYMGMVWAMMAIGLLGFIVWAHHMFTVGMDVD

Caenorhabditis elegans        YLTGKKEVFGALGMVYAILSIGLIGCVVWAHHMYTVGMDLD

Drosophila                    QESGKKETFGSLGMIYAMLAIGLLGFIVWAHHMFTVGMDVD

Slime mold                    KYS-NKGIFGVKGMISAMSAIGFLGFLVWAHHMYTVGLDVD

Baker's yeast                 TYS-KKPVFGEISMVYAMASIGLLGFLVWSHHMYIVGLDAD

Fission yeast                 SLA-HKPIFGKEGMLWAMLSIALLGLMVWSHHLFTVGLDVD

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 271 – 293 Helical; Name=7
Metal binding 290 – 290 Copper B
Metal binding 291 – 291 Copper B


Literature citations

Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia.
Gattermann N.; Retzlaff S.; Wang Y.L.; Hofhaus G.; Heinisch J.; Aul C.; Schneider W.;
Blood 90:4961-4972(1997)
Cited for: VARIANTS THR-273 AND THR-280; POSSIBLE INVOLVEMENT IN ACQUIRED IDIOPATHIC SIDEROBLASTIC ANEMIA;

MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase.
Broker S.; Meunier B.; Rich P.; Gattermann N.; Hofhaus G.;
Eur. J. Biochem. 258:132-138(1998)
Cited for: VARIANTS THR-273 AND THR-280; POSSIBLE INVOLVEMENT IN ACQUIRED IDIOPATHIC SIDEROBLASTIC ANEMIA;

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.