6ima

Structural highlights

Function

[ALKB1_MOUSE] Dioxygenase that acts as on nucleic acids, such as DNA and tRNA (PubMed:27027282, PubMed:27745969). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:27027282). A number of activities have been described for this dioxygenase, but recent results suggest that it mainly acts as on tRNAs and mediates their demethylation or oxidation depending on the context and subcellular compartment (By similarity). Mainly acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs, with a preference for N(1)-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs (PubMed:27745969). Acts as a regulator of translation initiation and elongation in response to glucose deprivation: regulates both translation initiation, by mediating demethylation of tRNA(Met), and translation elongation, N(1)-methyladenine-containing tRNAs being preferentially recruited to polysomes to promote translation elongation (By similarity). In mitochondrion, specifically interacts with mt-tRNA(Met) and mediates oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f(5)c) at this position (By similarity). mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation (By similarity). Specifically demethylates DNA methylated on the 6th position of adenine (N(6)-methyladenosine) DNA (PubMed:27027282). N(6)-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (PubMed:27027282). Demethylates mRNAs containing N(3)-methylcytidine modification (By similarity). Also able to repair alkylated single-stranded DNA by oxidative demethylation, but with low activity (By similarity). Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites (By similarity). DNA lyase activity does not require alpha-ketboglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5' DNA product (By similarity). DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation (PubMed:23825659). May play a role in placental trophoblast lineage differentiation (PubMed:18163532).[UniProtKB:Q13686]^{[1] [2] [3] [4]}

References

1. ↑ Pan Z, Sikandar S, Witherspoon M, Dizon D, Nguyen T, Benirschke K, Wiley C, Vrana P, Lipkin SM. Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Dev Dyn. 2008 Feb;237(2):316-27. doi: 10.1002/dvdy.21418. PMID:18163532 doi:http://dx.doi.org/10.1002/dvdy.21418
2. ↑ Muller TA, Yu K, Hausinger RP, Meek K. ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination. PLoS One. 2013 Jun 25;8(6):e67403. doi: 10.1371/journal.pone.0067403. Print 2013. PMID:23825659 doi:http://dx.doi.org/10.1371/journal.pone.0067403
3. ↑ Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M, Tackett A, Wang G, Hon LS, Fang G, Swenberg JA, Xiao AZ. DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature. 2016 Apr 21;532(7599):329-33. doi: 10.1038/nature17640. Epub 2016 Mar 30. PMID:27027282 doi:http://dx.doi.org/10.1038/nature17640
4. ↑ Liu F, Clark W, Luo G, Wang X, Fu Y, Wei J, Wang X, Hao Z, Dai Q, Zheng G, Ma H, Han D, Evans M, Klungland A, Pan T, He C. ALKBH1-Mediated tRNA Demethylation Regulates Translation. Cell. 2016 Oct 20;167(3):816-828.e16. doi: 10.1016/j.cell.2016.09.038. Epub 2016 , Oct 13. PMID:27745969 doi:http://dx.doi.org/10.1016/j.cell.2016.09.038