InterPro domain: IPR001199

Cytochrome b5 is a membrane-bound hemoprotein which acts as an electron carrier for several membrane-bound oxygenases [ 1 ]. There are two homologous forms of b5, one found in microsomes and one found in the outer membrane of mitochondria. Two conserved histidine residues serve as axial ligands for the heme group. The structure of a number of oxidoreductases consists of the juxtaposition of a heme-binding domain homologous to that of b5 and either a flavodehydrogenase or a molybdopterin domain. These enzymes are:

• Lactate dehydrogenase (EC 1.1.2.3) [ 2 ], an enzyme that consists of a flavodehydrogenase domain and a heme-binding domain called cytochrome b2.
• Nitrate reductase (EC 1.7.1.-), a key enzyme involved in the first step of nitrate assimilation in plants, fungi and bacteria [ 3 ]. Consists of a molybdopterin domain, a heme-binding domain called cytochrome b557, as well as a cytochrome reductase domain.
• Sulfite oxidase (EC 1.8.3.1) [ 4 ], which catalyzes the terminal reaction in the oxidative degradation of sulfur-containing amino acids. Also consists of a molybdopterin domain and a heme-binding domain.
• Yeast acyl-CoA desaturase 1 (EC 1.14.19.1; gene OLE1). This enzyme contains a C-terminal heme-binding domain.
• Yeast Scs7 (YMR272c), a sphingolipid alpha-hydroxylase.

Proteins containing a cytochrome b5-like domain also include:

• TU-36B, a Drosophila muscle protein of unknown function [ 5 ].
• Fission yeast hypothetical protein SpAC1F12.10c (C1F12.10c).
• Yeast Irc21 (YMR073c), a putative protein with unknown function.

1. Structure of cytochrome b5 and its topology in the microsomal membrane. Biochim. Biophys. Acta 997, 121-30
2. Structure, expression and regulation of a nuclear gene encoding a mitochondrial protein: the yeast L(+)-lactate cytochrome c oxidoreductase (cytochrome b2). EMBO J. 4, 3265-72
3. Sequence and nitrate regulation of the Arabidopsis thaliana mRNA encoding nitrate reductase, a metalloflavoprotein with three functional domains. Proc. Natl. Acad. Sci. U.S.A. 85, 5006-10
4. Amino acid sequence of the 'b5-like' heme-binding domain from chicken sulfite oxidase. Eur. J. Biochem. 100, 441-53
5. Structure and expression of a muscle specific gene which is adjacent to the Drosophila myosin heavy-chain gene and can encode a cytochrome b related protein. Nucleic Acids Res. 17, 6349-67