CYB5R3 (F1D9O) Rabbit mAb #84402

Cytochrome b5 reductase 3 (CYB5R3) is an essential flavoprotein that catalyzes the transfer of electrons from NADH to cytochrome b5. CYB5R3 is produced as two different isoforms: a membrane-bound form in somatic cells and a soluble form in erythrocytes (1). The membrane-bound form is found anchored primarily to the endoplasmic reticulum (ER) and is involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, and drug metabolism. The soluble form functions in methemoglobin reduction and the regulation of aerobic metabolism (1). CYB5R3 has been shown to be a UFM1 substrate, with UFMylation being dependent on interactions with the E3 ligase components UFL1 and UFBP1. UFMylated CYB5R3 is converted to its inactive form and degraded in lysosomes, leading to the induction of ER-phagy (2).

Mutations in the CYB5R3 gene can lead to both Type I and Type II methemoglobinemia, a rare genetic disorder characterized by elevated levels of methemoglobin in the blood, leading to chronic cyanosis and neurological dysfunction (3,4). Downregulation of CYB5R3 has been shown to promote tumorigenesis and lung metastasis in mouse models whereas overexpression can induce ER stress-mediated apoptosis, thus implicating CYB5R3 as a tumor suppressor (5). Additionally, CYB5R3 is essential for cardiomyocyte function and may have critical protective effects on vascular function and sudden cardiac death (6,7).