O00370 · LORF2_HUMAN

  • Protein
    LINE-1 retrotransposable element ORF2 protein
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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).

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.
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.

Catalytic activity

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site43Mg2+ 1 (UniProtKB | ChEBI)
Active site115
Active site145Proton donor/acceptor
Binding site600Mg2+ 2 (UniProtKB | ChEBI); catalytic
Binding site702Mg2+ 2 (UniProtKB | ChEBI); catalytic
Binding site703Mg2+ 2 (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Molecular Functionmetal ion binding
Molecular FunctionRNA binding
Molecular FunctionRNA-directed DNA polymerase activity
Molecular Functiontype II site-specific deoxyribonuclease activity
Biological ProcessDNA recombination
Biological Processnucleic acid metabolic process
Biological Processretrotransposition

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    LINE-1 retrotransposable element ORF2 protein
  • Short names
    ORF2p

Including 2 domains:

  • Recommended name
    Reverse transcriptase
  • EC number

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O00370

Proteomes

Organism-specific databases

Disease & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis14Loss of endonuclease activity and reduced transposition efficiency.
Mutagenesis43Loss of endonuclease activity.
Mutagenesis145Loss of endonuclease activity and reduced transposition efficiency. Reduced transposition efficiency; when associated with A-147.
Mutagenesis147Reduced transposition efficiency; when associated with A-145.
Mutagenesis155Reduced DNA nicking activity and reduced transposition efficiency.
Mutagenesis192Reduced transposition efficiency.
Mutagenesis202Reduced DNA nicking activity and reduced transposition efficiency.
Mutagenesis204Reduced DNA nicking activity and reduced transposition efficiency.
Mutagenesis205Loss of endonuclease activity and reduced transposition efficiency.
Mutagenesis226Increased endonuclease activity.
Mutagenesis230Loss of endonuclease activity and reduced transposition efficiency.
Mutagenesis703Reduced transposition efficiency.
Mutagenesis1130No effect on binding to RNA; when associated with R-1134, R-1143 and R-1147.
Mutagenesis1134No effect on binding to RNA; when associated with R-1130, R-1143 and R-1147.
Mutagenesis1143No effect on binding to RNA; when associated with R-1130, R-1134 and R-1147.
Mutagenesis1147No effect on binding to RNA; when associated with R-1130, R-1134 and R-1143.

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004250821-1275LINE-1 retrotransposable element ORF2 protein

Proteomic databases

PTM databases

Interaction

Subunit

Interacts with MOV10.

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region1-239Endonuclease activity
Domain498-773Reverse transcriptase
Region1096-1275Carboxy-terminal segment; binds RNA
Domain1242-1260DUF1725

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.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,275
  • Mass (Da)
    149,012
  • Last updated
    1997-07-01 v1
  • Checksum
    588703688E7129FF
MTGSNSHITILTLNVNGLNSPIKRHRLASWIKSQDPSVCCIQETHLTCRDTHRLKIKGWRKIYQANGKQKKAGVAILVSDKTDFKPTKIKRDKEGHYIMVKGSIQQEELTILNIYAPNTGAPRFIKQVLSDLQRDLDSHTLIMGDFNTPLSILDRSTRQKVNKDTQELNSALHQTDLIDIYRTLHPKSTEYTFFSAPHHTYSKIDHIVGSKALLSKCKRTEIITNYLSDHSAIKLELRIKNLTQSRSTTWKLNNLLLNDYWVHNEMKAEIKMFFETNENKDTTYQNLWDAFKAVCRGKFIALNAYKRKQERSKIDTLTSQLKELEKQEQTHSKASRRQEITKIRAELKEIETQKTLQKINESRSWFFERINKIDRPLARLIKKKREKNQIDTIKNDKGDITTDPTEIQTTIREYYKHLYANKLENLEEMDTFLDTYTLPRLNQEEVESLNRPITGSEIVAIINSLPTKKSPGPDGFTAEFYQRYKEELVPFLLKLFQSIEKEGILPNSFYEASIILIPKPGRDTTKKENFRPISLMNIDAKILNKILANRIQQHIKKLIHHDQVGFIPGMQGWFNIRKSINVIQHINRAKDKNHVIISIDAEKAFDKIQQPFMLKTLNKLGIDGMYLKIIRAIYDKPTANIILNGQKLEAFPLKTGTRQGCPLSPLLFNIVLEVLARAIRQEKEIKGIQLGKEEVKLSLFADDMIVYLENPIVSAQNLLKLISNFSKVSGYKINVQKSQAFLYNNNRQTESQIMGELPFTIASKRIKYLGIQLTRDVKDLFKENYKPLLKEIKEDTNKWKNIPCSWVGRINIVKMAILPKVIYRFNAIPIKLPMTFFTELEKTTLKFIWNQKRARIAKSILSQKNKAGGITLPDFKLYYKATVTKTAWYWYQNRDIDQWNRTEPSEIMPHIYNYLIFDKPEKNKQWGKDSLLNKWCWENWLAICRKLKLDPFLTPYTKINSRWIKDLNVKPKTIKTLEENLGITIQDIGVGKDFMSKTPKAMATKDKIDKWDLIKLKSFCTAKETTIRVNRQPTTWEKIFATYSSDKGLISRIYNELKQIYKKKTNNPIKKWAKDMNRHFSKEDIYAAKKHMKKCSSSLAIREMQIKTTMRYHLTPVRMAIIKKSGNNRCWRGCGEIGTLVHCWWDCKLVQPLWKSVWRFLRDLELEIPFDPAIPLLGIYPKDYKSCCYKDTCTRMFIAALFTIAKTWNQPNCPTMIDWIKKMWHIYTMEYYAAIKNDEFISFVGTWMKLETIILSKLSQEQKTKHRIFSLIGGN

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U93569
EMBL· GenBank· DDBJ
AAC51271.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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