CYP4 clan
The CYP4 clan genes are highly abundant in arthropod genomes, but paradoxically, one of the least studied in insects (Feyereisen, 2006). This remains the case. The size of the CYP4 clan is reduced in several lineages. While the honey bee and other Apoidea have just four CYP4 clan genes (Claudianos et al., 2006; Beadle et al., 2019), there are only two CYP4 clan genes in Tigriopus japonicus and none reported in the salmon louse Lepeophtheirus salmonis (Humble et al., 2019). The TSA of another copepod Paracylopina nana apparently lacks CYP4 clan genes (Han et al., 2015) and so does the TSA of Heterocypris incongruens (Ostracoda, ICLE01). Protura TSA are also depauperate in CYP4 sequences, with just one in Acerentomon sp., and perhaps just three in Sinentomon sp. However there are more than 50 CYP4 clan genes in Collembola or in the fall armyworm (table)
CYP316A1
CYP316A1 of Diptera has an unusual Cys pocket motif, YSLGPRCCPAR in Drosophila melanogaster and WGLGPRNCVAR in Ceratitis capitata (XP_004519952). This gene is poorly understood and expressed at very low levels in D. melanogaster. Good et al., (2014) consider this gene to be “stable” in the Drosophila lineage but while it is found in Drosophila relatives and in Tephritidae, it is not found in Calyptratae.
The gene is a CYP4 clan member located head to head with CYP4D8 in Drosophila melanogaster on 3L at 66A2, and tail to head with CYP4D8 in Tephritidae. In Calyptratae, CYP4D8 is present as tandem duplicates with the more usual conserved FSAGPRNCIGQ motif. The Cys-Pro dipeptide of the drosophilids is relatively rare in P450s. In Mycobacterium tuberculosis CYP121, a Pro at that position causes a kink in one of the pyrrole rings of the heme because of their close interactions (Leys et al., 2013). In the tephridid CYP316A1, the conserved Phe is replaced by an unusual Trp, which, in view of the close proximity of the usual Phe to the heme probably also affect heme conformation and redox properties as shown for P450 BM3 Phe mutants (Chen et al., 2004).
CYP316A1 probably catalyzes an unusual reaction or has an unusual type of substrate. While this gene is a fast evolving distant member of the CYP4 clan, it is not considered a CYP19 clan P450 as suggested by Kawashima and Hatta (2014).