The Cas9::HN1HB1 entry in FlyBase represents a fusion protein in which a Cas9 RNA-guided nuclease (derived from the naturally occurring Cas9 endonuclease from Streptococcus pyogenes and in which the two nuclease domains present in the naturally occurring protein are functional) is fused to the Homo sapiens HMGN1 gene (HGNC:4984) at its N-terminus and to an HMG box A domain from the Homo sapiens HMGB1 gene (HGNC:4983) at its C-terminus. The presence of the HMG sequences, which function as chromatin-modulating peptides (CMPs), increases the activity of Cas9::HN1HB1 compared to unmodified Cas9, particularly on refractory target sites (PMID:31021236). The exact sequence of the nuclease may differ depending on the particular transgene or modified endogenous locus being used, for example, the coding sequence may have been codon optimized for use in different species.