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P1cre(V336A)::PR encodes a ligand-inducible recombinase that is composed of the recombinase encoded by the cre locus of the bacteriophage P1 genome fused to ligand-binding domain sequence (amino acid residues 650-914) from the Homo sapiens progesterone receptor (PGR, HGNC:8910). The presence of the PGR ligand-binding domain results in recombinase activity being dependent on the presence of the synthetic ligand RU486. The cre recombinase sequence lacks the first 18 amino acids and contains a V336A amino acid change that removes a cryptic splice donor site at the 3' end of the cre coding sequence. The latter mutation reduces background recombinase activity in the absence of RU486 to an almost undetectable level (PMID:11353092). Upon activation, P1cre(V336A)::PR mediates recombination between a pair of specific target sites, with compatible target sites corresponding to the wild-type loxP site and some of its derivatives. Recombination occurs between a pair of target sites oriented in the same direction; the 13bp repeats each act as binding sites for the recombinase, while the asymmetric 8bp spacer is the site of DNA strand exchange and determines the orientation of the target site (PMID:3856690). The recombination event catalyzed by P1cre(V336A)::PR results in genetic modification, the nature of which is influenced by the relative orientation (direct or inverted), location and composition of the two target sites. The types of possible modification include deletion of DNA and generation of chromosomal rearrangements (reviewed in FBrf0231034).

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