====== CYP2 Clan ======

The CYP2 clan has in general //few// genes in insects, but //many// genes in chelicerates, crustacea and collembola ([[https://www.sciencedirect.com/science/article/pii/S096517482030179X|Dermauw et al., 2020]]), see the [[cypfam_by_clan|distribution of CYP sequences by clan]]. Several CYP families of the CYP2 clan are involved in essential physiological functions, while others particularly in Chelicerates, are typical xenobiotic metabolizing P450 (see [[functions|functions]]).

[[cyp307page|CYP307]], [[cyp18and306page|CYP18]] and [[cyp18and306page|CYP306]] are involved in [[ecdysteroid_metabolism|ecdysteroid metabolism]].


===== CYP15 =====

The [[CYP15|CYP15]] family includes orthologs of CYP15A1 initially described in //Diploptera punctata// and involved in the epoxidation of Juvenile Hormone precursors.


===== CYP305 =====


Next to CYP15A/C in the phylogeny is the CYP305 clade. Synteny relationships indicate that CYP15 and CYP305 are neighbouring genes and that this synteny is recognizable from termites to mosquitoes.
{{ ::cyp15locus.jpg?500 |}}      __Phylogeny of the CYP15/CYP305 locus__ //(Fig. S5 from Dermauw et al., 2020)//


The function of the CYP305 genes is still unknown, but they are found in most Neoptera as a single gene. 

In gregarious locusts, one of the paralogs, CYP305M2, controls biosynthesis of the defense compound phenylacetonitrile (Wei et al., 2019), suggesting that it plays a regulatory role in phase determination.


===== CYP303 =====

CYP303A1 is a strongly supported clade with generally a single gene for each species, but it is duplicated in the Argentine ant, //Linepithema humile//, and in the carpenter ant //Camponotus floridanus// where the two genes are in a tandem array. It is also duplicated in the damselfly //Calopteryx splendens//. CYP303 was not found in genomes or TSA beyond winged insects.
The CYP303A1 are highly conserved with a 498 __+__ 4 amino acids length, yet the hymenopteran orthologs are much longer (//Apis mellifera// 562 aa, //Nasonia vitripennis// 587 aa). The difference is a single long insertion, confirmed by TSA of a variety of species. This insertion is predicted to be located between helices D and E, thus on the outside of the globular P450 structure and away from the ER membrane surface. Its endogenous substrate is still unknown, but the conserved regulatory function of the gene in Drosophila and locusts point to a signal molecule, possibly a hormone (Wu et al., 2019; 2020b). 

With possibly more exceptions as noted above, CYP303A1 is mostly a single copy gene, “stable” in insects, yet there is a bloom of CYP303 genes in [[photinus_pyralis|fireflies]] (Fallon et al., 2018). The genome of //Photinus pyralis// carries 16 genes and two pseudogenes that are all paralogs of CYP303A1. This appears to be related to the biosynthesis of defensive compounds (lucibufagins). 


Shi et al., 2022 reported modest O-demethylation activity of //Helicoverpa armigera// CYP303A1 towards 7-benzyloxymethoxy resorufin (BOMR), and a significant metabolism of 2-tridecanone (although the metabolic product of the reaction was not identified).