The following text describes a protein:
Function:
Has reverse transcriptase activity required for target-primed reverse transcription of the LINE-1 element mRNA, a crucial step in LINE-1 retrotransposition. Selectively binds and reversely transcribes RNA with a poly(A) tail consisting of at least 20 adenosines. Also has endonuclease activity that allows the introduction of nicks in the chromosomal target DNA. Cleaves DNA in AT-rich regions between a 5' stretch of purines and a 3' stretch of pyrimidines, corresponding to the sites of LINE-1 integration in the genome. Conformational properties of the target DNA sequence rather than specific nucleotides are key determinants of the ORF2p capacity for sequence-specific DNA recognition. Unlike related endonucleases, does not bend the DNA helix but causes compression near the cleavage site.
Miscellaneous:
MISCELLANEOUS: Long interspersed element-1/LINE-1/L1 retrotransposons are present in more than 500'000 full (6 kb) or truncated copies in the human genome. Most of them are inactive but one estimate is that 80 to 100 of those elements could be transcribed, translated and active in any individual. An active LINE-1 encodes for 2 proteins translated from a single RNA containing two non-overlapping ORFs, ORF1 and ORF2. ORF2p is described in this entry as a representative of all ORF2p potentially expressed by active elements. ORF1p is described in the related entry AC Q9UN81; MISCELLANEOUS: Insertions of LINE-1 (L1) retrotransposons can occur frequently at CRISPR/Cas9 editing sites. The reverse transcriptase activity of ORF2p mediates L1 insertions into CRISPR/Cas9-initiated double-strand breaks (DSB). De novo L1 insertions are rare during genome editing by prime editors and by cytidine or adenine base editors, consistent with their reduced DSB formation.
Domain:
The FADD motif is located within the catalytic core and is essential for reverse transcriptase activity. 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.
Sequence:
MTGSNSHITILTLNVNGLNSPIKRHRLASWIKSQDPSVCCIQETHLTCRDTHRLKIKGWRKIYQANGKQKKAGVAILVSDKTDFKPTKIKRDKEGHYIMVKGSIQQEELTILNIYAPNTGAPRFIKQVLSDLQRDLDSHTLIMGDFNTPLSILDRSTRQKVNKDTQELNSALHQTDLIDIYRTLHPKSTEYTFFSAPHHTYSKIDHIVGSKALLSKCKRTEIITNYLSDHSAIKLELRIKNLTQSRSTTWKLNNLLLNDYWVHNEMKAEIKMFFETNENKDTTYQNLWDAFKAVCRGKFIALNAYKRKQERSKIDTLTSQLKELEKQEQTHSKASRRQEITKIRAELKEIETQKTLQKINESRSWFFERINKIDRPLARLIKKKREKNQIDTIKNDKGDITTDPTEIQTTIREYYKHLYANKLENLEEMDTFLDTYTLPRLNQEEVESLNRPITGSEIVAIINSLPTKKSPGPDGFTAEFYQRYKEELVPFLLKLFQSIEKEGILPNSFYEASIILIPKPGRDTTKKENFRPISLMNIDAKILNKILANRIQQHIKKLIHHDQVGFIPGMQGWFNIRKSINVIQHINRAKDKNHVIISIDAEKAFDKIQQPFMLKTLNKLGIDGMYLKIIRAIYDKPTANIILNGQKLEAFPLKTGTRQGCPLSPLLFNIVLEVLARAIRQEKEIKGIQLGKEEVKLSLFADDMIVYLENPIVSAQNLLKLISNFSKVSGYKINVQKSQAFLYNNNRQTESQIMGELPFTIASKRIKYLGIQLTRDVKDLFKENYKPLLKEIKEDTNKWKNIPCSWVGRINIVKMAILPKVIYRFNAIPIKLPMTFFTELEKTTLKFIWNQKRARIAKSILSQKNKAGGITLPDFKLYYKATVTKTAWYWYQNRDIDQWNRTEPSEIMPHIYNYLIFDKPEKNKQWGKDSLLNKWCWENWLAICRKLKLDPFLTPYTKINSRWIKDLNVKPKTIKTLEENLGITIQDIGVGKDFMSKTPKAMATKDKIDKWDLIKLKSFCTAKETTIRVNRQPTTWEKIFATYSSDKGLISRIYNELKQIYKKKTNNPIKKWAKDMNRHFSKEDIYAAKKHMKKCSSSLAIREMQIKTTMRYHLTPVRMAIIKKSGNNRCWRGCGEIGTLVHCWWDCKLVQPLWKSVWRFLRDLELEIPFDPAIPLLGIYPKDYKSCCYKDTCTRMFIAALFTIAKTWNQPNCPTMIDWIKKMWHIYTMEYYAAIKNDEFISFVGTWMKLETIILSKLSQEQKTKHRIFSLIGGN