Cytochrome b5 (CYB5A)
The protein contains 134 amino acids for an estimated molecular weight of 15330 Da.
Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases. (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| METAG |
Biological Process
L-ascorbic acid metabolic process
Protein insertion into ER membrane
Response to cadmium ion
The reference OMIM entry for this protein is 250790
Methemoglobinemia type iv
Methemoglobinemia due to deficiency of cytochrome b5
A number sign (#) is used with this entry because of evidence that methemoglobin type IV is caused by mutation in the microsomal cytochrome b5 gene (CYB5A; 613218). One genetically confirmed patient has been reported. See also the more common autosomal recessive methemoglobinemias types I and II (250800), which are caused by mutation in the cytochrome b5 reductase gene (CYB5R3; 613213).
CLINICAL FEATURES
Hegesh et al. (1986) described the highly instructive case of a female Yemenite Jewish baby who turned blue at 7 days of age and was persistently cyanotic for her 26 years to the time of report. There were no neurologic symptoms. Giordano et al. (1994) reported in full on the findings in this patient, who was said to be the only example of type IV methemoglobinemia described. Hegesh et al. (1986) had reported that the parents and 6 sibs had normal methemoglobin levels, whereas those in the patient varied between 12% and 19%. The patient's erythrocyte cytochrome b5 levels were about 25% of those found in other family members. Polyacrylamide gel electrophoresis of cytochrome b5 from the patient and family members demonstrated no differences in mobility. The patient exhibited female genitalia at birth but was subsequently determined to be a male pseudohermaphrodite. Giordano et al. (1994) suggested that the pseudohermaphroditism was also caused by the cytochrome b5 defect. Androgen deficiencies due to defects in 17-alpha-hydroxylase activity are a known cause of pseudohermaphroditism in males (202110), and cytochrome b5 has been shown to participate in 17-alpha hydroxylation in adrenal steroidogenesis by serving as an electron donor.BIOCHEMICAL FEATURES
Laboratory studies of the patient reported by Hegesh et al. (1986) showed that adding the cofactor cytochrome b5 restored methemoglobin reductase activity. Cytochrome b5 was very low in the patient's red cells but was normal in the healthy unrelated parents and in the sibs. No abnormality of electrophoresis or heat stability was found. The findings in this patient provided confirmation for the conclusion of Hultquist and Passon (1971) that cytochrome b5 is required for methemoglobin reduction in vivo. The lack of neurologic symptoms in the patient suggested that membrane-bound cytochrome b5 levels in nucleated cells, at least those of the brain, were normal (Charache, 1986).MOLECULAR GENETICS
In a patient with type IV hereditary methemoglobinemia originally reported by Hegesh et al. (1986), Steggles et al. (1992) identified a homozygous splice site mutation in the CYB5A gene (613218.0001), resulting in premature termination of the protein. Steggles et al. (1992) indicated that whereas more than 300 patients had been reported with hereditary methemoglobinemia types I or II (250800), only 1 case of type IV had been reported. The rarity may be due to lethality of most type IV mutations. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 250790 was added.
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).