An RNA-guided dsDNA endonuclease. When guided by an RNA derived from the right-end element of its insertion sequence element (IS), cleaves DNA downstream of the 5'-TTGAT-3' transposon-associated motif (TAM). Cleaves supercoiled and linear DNA in a staggered manner 15-21 bases from the TAM yielding 5'-overhangs. Binds reRNA, an approximately 150 nucleotide base sRNA derived from the 3' end of its own gene, the right end (RE) of the insertion sequence (IS) and sequence downstream of the IS (PubMed:34619744). May cleave at the donor joint (generated by ISDra2 excision mediated by TnpA) to trigger homology-directed repair and restore intact IS in its original position (Probable). Inhibits transposition activity of the IS200 element; the possible zinc-binding motif of TnpB is required for this inhibition (PubMed:23461641). Part of IS element ISDra2, this protein is not required for transposition (PubMed:20090938). The IS element inserts 3' of the sequence 5'-TTGAT-3'; target duplication has not been observed (PubMed:14676423, PubMed:16359337). Monomer. When tested in an R1 strain with only a single IS200 element (DR_1651 and DR_1652), not required for transposition of this IS element. Single tnpA or double tnpA-tnpB deletion leads to loss of transposition. Has been shown to cleave dsDNA in a targeted manner in human (HEK293T) cells, suggesting it could be used for genome editing. Belongs to the IS200/IS605 insertion sequence (IS) element family, formerly called IS8301 (PubMed:14676423, PubMed:20090938). This element is subject to strain polymorphism; in the ATCC 13939 / R1 strain genome sequenced by White there are 7 complete and 1 incomplete IS200/IS605 elements (PubMed:10567266). Another R1 strain has only 1 copy of this element (PubMed:14676423, PubMed:20090938). Another group found 2 copies of this element in untreated R1 strains (PubMed:16359337, PubMed:10567266, PubMed:14676423, PubMed:20090938). This class of protein is thought to probably be the ancestor of Cas9 and Cas12 CRISPR endonucleases. In the N-terminal section; belongs to the transposase 2 family. In the C-terminal section; belongs to the transposase 35 family. Has been suggested to both inhibit transposition and possibly enhance transposition.