LORF2_HUMAN
Domain
The C-terminal segment (CTS) binds to RNA with high affinity in the nanomolar range but without apparent sequence specificity.
The size and flexibility of the betaB6-betaB5 hairpin loop at residues 191-205 are crucial for activity. Variation of the loop sequence results in an altered DNA nicking profile including novel sites.
Function
Has reverse transcriptase activity required for target-primed reverse transcription of the LINE-1 element mRNA, a crucial step in LINE-1 retrotransposition (PubMed:7516468, PubMed:9140393). Also has endonuclease activity that allows the introduction of nicks in the chromosomal target DNA (PubMed:17626046, PubMed:34554261, PubMed:8945517). Cleaves DNA in AT-rich regions between a 5' stretch of purines and a 3' stretch of pyrimidines, corresponding to sites of LINE-1 integration in the genome (PubMed:8945517). Conformational properties of the target DNA sequence rather than specific nucleotides are key determinants of the ORF2p capacity for sequence-specific DNA recognition (PubMed:17626046, PubMed:34554261). Unlike related endonucleases, does not bend the DNA helix but causes compression near the cleavage site (PubMed:34554261).
Alternative names
LINE-1 retrotransposable element ORF2 protein, ORF2p