Cytochrome P450, E-class, group I, CYP1 (IPR008066)
Short name: Cyt_P450_E_grp-I_CYP1
Overlapping homologous superfamilies
Cytochrome P450 enzymes are a superfamily of haem-containing mono-oxygenases that are found in all kingdoms of life, and which show extraordinary diversity in their reaction chemistry. In mammals, these proteins are found primarily in microsomes of hepatocytes and other cell types, where they oxidise steroids, fatty acids and xenobiotics, and are important for the detoxification and clearance of various compounds, as well as for hormone synthesis and breakdown, cholesterol synthesis and vitamin D metabolism. In plants, these proteins are important for the biosynthesis of several compounds such as hormones, defensive compounds and fatty acids. In bacteria, they are important for several metabolic processes, such as the biosynthesis of antibiotic erythromycin in Saccharopolyspora erythraea (Streptomyces erythraeus).
Cytochrome P450 enzymes use haem to oxidise their substrates, using protons derived from NADH or NADPH to split the oxygen so a single atom can be added to a substrate. They also require electrons, which they receive from a variety of redox partners. In certain cases, cytochrome P450 can be fused to its redox partner to produce a bi-functional protein, such as with P450BM-3 from Bacillus megaterium [PMID: 17023115], which has haem and flavin domains.
Organisms produce many different cytochrome P450 enzymes (at least 58 in humans), which together with alternative splicing can provide a wide array of enzymes with different substrate and tissue specificities. Individual cytochrome P450 proteins follow the nomenclature: CYP, followed by a number (family), then a letter (subfamily), and another number (protein); e.g. CYP3A4 is the fourth protein in family 3, subfamily A. In general, family members should share >40% identity, while subfamily members should share >55% identity.
Cytochrome P450 proteins can also be grouped by two different schemes. One scheme was based on a taxonomic split: class I (prokaryotic/mitochondrial) and class II (eukaryotic microsomes). The other scheme was based on the number of components in the system: class B (3-components) and class E (2-components). These classes merge to a certain degree. Most prokaryotes and mitochondria (and fungal CYP55) have 3-component systems (class I/class B) - a FAD-containing flavoprotein (NAD(P)H-dependent reductase), an iron-sulphur protein and P450. Most eukaryotic microsomes have 2-component systems (class II/class E) - NADPH:P450 reductase (FAD and FMN-containing flavoprotein) and P450. There are exceptions to this scheme, such as 1-component systems that resemble class E enzymes [PMID: 16042601, PMID: 15128046, PMID: 8637843]. The class E enzymes can be further subdivided into five sequence clusters, groups I-V, each of which may contain more than one cytochrome P450 family (eg, CYP1 and CYP2 are both found in group I). The divergence of the cytochrome P450 superfamily into B- and E-classes, and further divergence into stable clusters within the E-class, appears to be very ancient, occurring before the appearance of eukaryotes.
This entry represents the CYP1 family from group I, class E, cytochrome P450 proteins. CYP1 enzymes mainly metabolise exogenous substrates and are found in mammalia (1A, 1B), bony fishes (1A), sharks, skates, rays (1A) and birds (1A). CYP1A contains five proteins, namely, CYP1A1, 1A2, 1A3, 1A4 and 1A5. CYP1 family members are closely associated with the metabolic activation of pro-carcinogens and mutagens [PMID: 16485905]. For example, CYP1B1 may play an important role in susceptibility to mammary and ovarian cancer through its involvement in oestrogen metabolism [PMID: 16112414], as well as with various cancers associated with the activation of polycyclic aromatic hydrocarbons in cigarette smoke [PMID: 16922636].
GO:0055114 oxidation-reduction process
GO:0020037 heme binding
GO:0005506 iron ion binding
GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
No terms assigned in this category.
- PR01683 (EP450ICYP1A)