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UniProtKB/Swiss-Prot P00387: Variant p.Ser128Pro

NADH-cytochrome b5 reductase 3
Gene: CYB5R3
Variant information

Variant position:  128
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 128 (S128P, p.Ser128Pro).
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:  Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800]: A form of methemoglobinemia, a hematologic disease characterized by the presence of excessive amounts of methemoglobin in blood cells, resulting in decreased oxygen carrying capacity of the blood, cyanosis and hypoxia. There are two types of methemoglobinemia CYB5R3-related. In type 1, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type 2, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes and all body tissues. Type 2 methemoglobinemia is associated with mental deficiency and other neurologic symptoms. {ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:12393396, ECO:0000269|PubMed:1400360, ECO:0000269|PubMed:15622768, ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1707593, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:7718898, ECO:0000269|PubMed:8119939, ECO:0000269|PubMed:9695975, ECO:0000269|PubMed:9886302}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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 METHB-CYB5R3; type 2; Hiroshima.
Any additional useful information about the variant.

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

Sequence information

Variant position:  128
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.






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.

Chain 2 – 301 NADH-cytochrome b5 reductase 3 membrane-bound form
Chain 27 – 301 NADH-cytochrome b5 reductase 3 soluble form
Domain 40 – 152 FAD-binding FR-type
Modified residue 120 – 120 N6-acetyllysine
Helix 126 – 133

Literature citations

Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase.
Yubisui T.; Shirabe K.; Takeshita M.; Kobayashi Y.; Fukumaki Y.; Sakaki Y.; Takano T.;
J. Biol. Chem. 266:66-70(1991)
Cited for: VARIANT METHB-CYB5R3 PRO-128;

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.