The cyc1 gene is located on the q arm of chromosome 8 in position 24.3 and has 8 exons. The cyc1 gene produces a 13.5 kDa protein composed of 130 amino acids. CYC1 belongs to the cytochrome c family.
Protein
CYC1 is a phosphoprotein which binds heme groups as ligands. It consists of a helix domain, a signal peptide domain, and a transmembrane domain, and contains 9 alpha helices, 5 beta strands, and 3 turns. The transmembrane protein passes through the inner mitochondrial membrane once and the majority of the protein is found on the intermembrane side. CYC1 contains covalent heme binding sites at positions 121 and 124 and heme axial ligand iron-metal binding sites at positions 125 and 244.
Function
Cytochrome C1 plays a role in the electron transfer during oxidative phosphorylation. As an iron-sulfur protein approaches the bc1 complex, it accepts an electron from the cytochrome b subunit, then undergoes a conformational change to attach to cytochrome c1. There, the electron carried by the iron-sulfur protein is transferred to the heme carried by cytochrome c1. This electron is then transferred to a heme carried by cytochrome c. This creates a reduced species of cytochrome c, which separates from the bc1 complex and moves to the last enzyme in the electron transport chain, cytochrome c oxidase (Complex IV).
In its structure and function, the cytochrome bc1 complex bears extensive analogy to the cytochrome b6f complex of chloroplasts and cyanobacteria; cytochrome c1 plays an analogous role to cytochrome f, despite their different structures.
Clinical relevance
Mutations in the cyc1 gene are associated with Mitochondrial Complex III deficiency, nuclear type 6 (MC3DN6), which is an autosomal-recessive disease. This results in a defect in Complex III, leading to instability, which decreases its activity in oxidative phosphorylation. The disease symptoms include early childhood onset of severe lactic acidosis and ketoacidosis, usually in response to infection. Insulin-responsive hyperglycemia is also present, but psychomotor development appears normal. Pathogenic mutations have included c.288G>T p.Trp96Cys, and c.643C>T p.Leu215Phe.
CYC1 has 78 protein-protein interactions, with 72 of them being co-complex interactions. CYC1 is one of 11 subunits of the bc1 complex, along with cytochrome b, UQCRFS1, the core proteins UQCRC1 and UQCRC2, and the low-molecular weight proteins UQCRH, UQCRB, UQCRQ, UQCR10, UQCR11, as well as an additional cleavage product of UQCRFS1. Additionally, CCP1, CDKA-1, and CDKB1-1 have also been found to interact with CYC1.
