LINE-1 retrotransposable element ORF2 protein

Involved in reverse transcription involved in RNA-mediated transposition

Involved in nucleic acid phosphodiester bond hydrolysis

Loss of endonuclease activity and reduced transposition efficiency.

Enables type II site-specific deoxyribonuclease activity

Enables RNA-directed DNA polymerase activity

a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1)

The carboxy-terminal segment (CTS) binds to RNA with high affinity in the nanomolar range but without apparent sequence specificity.

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.

Loss of endonuclease activity and reduced transposition efficiency. Reduced transposition efficiency; when associated with A-147.

Reduced transposition efficiency; when associated with A-145.

Reduced DNA nicking activity and reduced transposition efficiency.

No effect on binding to RNA; when associated with R-1134, R-1143 and R-1147.

No effect on binding to RNA; when associated with R-1130, R-1143 and R-1147.

No effect on binding to RNA; when associated with R-1130, R-1134 and R-1147.

No effect on binding to RNA; when associated with R-1130, R-1134 and R-1143.

Has reverse transcriptase activity required for target-primed reverse transcription of the LINE-1 element mRNA, a crucial step in LINE-1 retrotransposition (PubMed:9140393, PubMed:7516468). Also has endonuclease activity that allows the introduction of nicks in the chromosomal target DNA (PubMed:8945517, PubMed:17626046, PubMed:34554261). 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).

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.

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.

2'-deoxyribonucleoside 5'-triphosphate(4-)

Involved in negative regulation of signaling receptor activity

Involved in negative regulation of execution phase of apoptosis

Involved in cellular response to staurosporine

Involved in negative regulation of mitochondrial membrane permeability involved in apoptotic process

Plays a role as a neuroprotective and antiapoptotic factor.

Down-regulated 6 hours following staurosporine (STS) treatment and up-regulated 24 hours following STS treatment. Down-regulated 6 hours following beta-carotene treatment, remains down-regulated 24 hours following beta-carotene treatment.

The humanin peptide has been shown to be biologically active but is the product of a mitochondrial gene, MT-RNR2. The mechanisms allowing the production and the secretion of humanin from the mitochondrial gene remaining unclear, the possibility exist that the physiologically active humanin peptide is encoded by one of the related genes present in the nuclear genome including the one described here (PubMed:19477263).

DUX genes are present in 3.3-kilobase elements, a tandem repeat family scattered in the genome found on the short arms of all acrocentric chromosomes as well as on several other chromosomes. May be functional despite lack of introns and a poly(A) addition signal.

DUX genes are present in 3.3-kilobase elements, a tandem repeat family scattered in the genome found on the short arms of all acrocentric chromosomes as well as on several other chromosomes. May be functional despite lack of introns and of a poly(A) addition signal.

LINE-1 retrotransposable element ORF1 protein

Located in cytoplasmic ribonucleoprotein granule

Loss of LINE-1 retrotransposition without affecting RNA-binding; when associated with A-123.

Loss of RNA-binding activity; when associated with A-206 and A-210.

Polyubiquitinated, probably by UBR2, which induces its degradation.

Loss of LINE-1 retrotransposition with decreased RNA-binding; when associated with S-133, A-137 and A-140.

Loss of LINE-1 retrotransposition with decreased RNA-binding.

The coiled coil domain mediates homotrimerization.

The RRM and the CTD domain are both required for proper RNA-binding activity.

No effect on cytoplasmic localization, may increase nucleolar localization.

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 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 2 non-overlapping ORFs, ORF1 and ORF2. ORF1p is described in this entry as a representative of all ORF1p potentially expressed by active elements. ORF2p is described in the related entry AC O00370.

Loss of RNA-binding activity; when associated with A-210 and A-211.

Small decrease in localization to stress granules.

Decreased localization to stress granules. Complete loss of localization to stress granules, slightly increased localization to the nucleus; when associated with A-157.

Loss of LINE-1 retrotransposition with decreased RNA-binding; when associated with A-137, A-140 and S-141.

Loss of LINE-1 retrotransposition with decreased RNA-binding; when associated with S-133, A-140 and S-141.

Loss of LINE-1 retrotransposition without affecting RNA-binding.

Homotrimer (via coiled coil domain). May also form larger homooligomers. May interact with DDX39A, HNRNPA1, SERBP1 and YBX1. Interacts with TEX19 and UBR2 (PubMed:28806172). Interacts with MOV10 (PubMed:23093941). Interacts with APOBEC3D; this interaction inhibits LINE-1 retrotransposition (PubMed:27428332).

Small decrease in localization to stress granules; when associated with A-93 and A-114.

Loss of LINE-1 retrotransposition without affecting RNA-binding; when associated with I-135 and I-142.

No effect on subcellular localization; when associated with A-155. Complete loss of localization to stress granules, slightly increased localization to the nucleus; when associated with G-159.

Loss of RNA-binding activity; when associated with A-206 and A-211.

Loss of LINE-1 retrotransposition without affecting RNA-binding; when associated with A-116.

Loss of LINE-1 retrotransposition without effect on RNA-binding; when associated with I-132 and I-135.

Loss of LINE-1 retrotransposition with decreased RNA-binding; when associated with S-133, A-137 and S-141.

Small decrease in localization to stress granules; when associated with A-100 and A-114.

Loss of LINE-1 retrotransposition without effect on RNA-binding; when associated with I-132 and I-142.

Small decrease in localization to stress granules; when associated with A-93 and A-100.

No effect on subcellular localization; when associated with A-157.

Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. Functions as a nucleic acid chaperone binding its own transcript and therefore preferentially mobilizing the transcript from which they are encoded.

Colocalizes with its encoding RNA in cytoplasmic ribonucleoprotein particle (PubMed:16183655). Mainly cytoplasmic, rarely detected in the nucleus, possibly within the nucleolus (PubMed:17562864).