Home  |  Contact

UniProtKB/Swiss-Prot O75880: Variant p.Pro174Leu

Protein SCO1 homolog, mitochondrial
Gene: SCO1
Variant information

Variant position:  174
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Proline (P) to Leucine (L) at position 174 (P174L, p.Pro174Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 MC4DN4; no effect on synthesis of cytochrome c oxidase subunit II; reduced stability of newly synthesized cytochrome c oxidase subunit II; reduced copper-binding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  174
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  301
The length of the canonical sequence.

Location on the sequence:   DYLGQWLLIYFGFTHCPDVC  P EELEKMIQVVDEIDSITTLP
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                         DYLGQWLLIYFGFTHCPDVCPEELEKMIQVVDEIDSITTLP

Mouse                         DYLGQWVLIYFGFTHCPDICPEELEKMIEVVEEIDSIPSLP

Bovine                        DYLGQWVLIYFGFTHCPDICPEELEKMIQVVDEIDSIPTLP

Baker's yeast                 NLLGKFSIIYFGFSNCPDICPDELDKLGLWLNTLSSKYGI-

Fission yeast                 DFKGKFSLIYFGFTRCPDICPDELDKMSAAIDIVNNVVGD-

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 68 – 301 Protein SCO1 homolog, mitochondrial
Topological domain 112 – 301 Mitochondrial intermembrane
Metal binding 169 – 169 Copper
Metal binding 173 – 173 Copper
Helix 172 – 189


Literature citations

The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis.
Leary S.C.; Cobine P.A.; Kaufman B.A.; Guercin G.H.; Mattman A.; Palaty J.; Lockitch G.; Winge D.R.; Rustin P.; Horvath R.; Shoubridge E.A.;
Cell Metab. 5:9-20(2007)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MC4DN4 LEU-174;

Human SCO2 is required for the synthesis of CO II and as a thiol-disulphide oxidoreductase for SCO1.
Leary S.C.; Sasarman F.; Nishimura T.; Shoubridge E.A.;
Hum. Mol. Genet. 18:2230-2240(2009)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MC4DN4 LEU-174;

Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy.
Valnot I.; Osmond S.; Gigarel N.; Mehaye B.; Amiel J.; Cormier-Daire V.; Munnich A.; Bonnefont J.-P.; Rustin P.; Rotig A.;
Am. J. Hum. Genet. 67:1104-1109(2000)
Cited for: VARIANT MC4DN4 LEU-174;

Human Sco1 functional studies and pathological implications of the P174L mutant.
Banci L.; Bertini I.; Ciofi-Baffoni S.; Leontari I.; Martinelli M.; Palumaa P.; Sillard R.; Wang S.;
Proc. Natl. Acad. Sci. U.S.A. 104:15-20(2007)
Cited for: CHARACTERIZATION OF VARIANT MC4DN4 LEU-174;

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.