ID ALKB1_HUMAN Reviewed; 389 AA. AC Q13686; Q8TAU1; Q9ULA7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 27-MAR-2024, entry version 179. DE RecName: Full=Nucleic acid dioxygenase ALKBH1 {ECO:0000305}; DE EC=1.14.11.- {ECO:0000269|PubMed:27497299}; DE AltName: Full=Alkylated DNA repair protein alkB homolog 1 {ECO:0000303|PubMed:19959401}; DE AltName: Full=Alpha-ketoglutarate-dependent dioxygenase ABH1 {ECO:0000303|PubMed:19959401}; DE AltName: Full=DNA 6mA demethylase {ECO:0000250|UniProtKB:P0CB42}; DE AltName: Full=DNA N6-methyl adenine demethylase ALKBH1 {ECO:0000305}; DE EC=1.14.11.51 {ECO:0000269|PubMed:30017583}; DE AltName: Full=DNA lyase ABH1 {ECO:0000303|PubMed:19959401}; DE EC=4.2.99.18 {ECO:0000305|PubMed:19959401}; DE AltName: Full=DNA oxidative demethylase ALKBH1; DE EC=1.14.11.33 {ECO:0000305|PubMed:18603530}; DE AltName: Full=mRNA N(3)-methylcytidine demethylase {ECO:0000305}; DE EC=1.14.11.- {ECO:0000305|PubMed:31188562}; GN Name=ALKBH1 {ECO:0000312|HGNC:HGNC:17911}; GN Synonyms=ABH {ECO:0000303|PubMed:17979886}, ABH1 GN {ECO:0000303|PubMed:19959401}, ALKBH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Synovial sarcoma; RX PubMed=8600462; DOI=10.1093/nar/24.5.931; RA Wei Y.F., Carter K.C., Wang R.P., Shell B.K.; RT "Molecular cloning and functional analysis of a human cDNA encoding an RT Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage RT repair."; RL Nucleic Acids Res. 24:931-937(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17979886; DOI=10.1111/j.1582-4934.2007.00094.x; RA Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., RA Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H.; RT "Expression and sub-cellular localization of human ABH family molecules."; RL J. Cell. Mol. Med. 11:1105-1116(2007). RN [5] RP FUNCTION, COFACTOR, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-218; HIS-231; RP ASP-233; HIS-287; ARG-338 AND ARG-344, IDENTIFICATION BY MASS SPECTROMETRY, RP AND TISSUE SPECIFICITY. RX PubMed=18603530; DOI=10.1074/jbc.m803776200; RA Westbye M.P., Feyzi E., Aas P.A., Vagbo C.B., Talstad V.A., Kavli B., RA Hagen L., Sundheim O., Akbari M., Liabakk N.B., Slupphaug G., Otterlei M., RA Krokan H.E.; RT "Human AlkB homolog 1 is a mitochondrial protein that demethylates 3- RT methylcytosine in DNA and RNA."; RL J. Biol. Chem. 283:25046-25056(2008). RN [6] RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF HIS-231; ASP-233 AND HIS-287. RX PubMed=19959401; DOI=10.1016/j.dnarep.2009.10.011; RA Muller T.A., Meek K., Hausinger R.P.; RT "Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic RT sites."; RL DNA Repair 9:58-65(2010). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=22961808; DOI=10.1002/stem.1228; RA Ougland R., Lando D., Jonson I., Dahl J.A., Moen M.N., Nordstrand L.M., RA Rognes T., Lee J.T., Klungland A., Kouzarides T., Larsen E.; RT "ALKBH1 is a histone H2A dioxygenase involved in neural differentiation."; RL Stem Cells 30:2672-2682(2012). RN [9] RP FUNCTION, AND MUTAGENESIS OF LYS-3; LYS-25; LYS-55; LYS-61; LYS-64; LYS-87; RP LYS-94; LYS-116; LYS-120; LYS-125; LYS-133; LYS-137; LYS-148; LYS-154; RP LYS-158; LYS-167; LYS-182; LYS-183; LYS-241; LYS-335; LYS-362 AND LYS-381. RX PubMed=23577621; DOI=10.1042/bj20121908; RA Mueller T.A., Andrzejak M.M., Hausinger R.P.; RT "A covalent protein-DNA 5'-product adduct is generated following AP lyase RT activity of human ALKBH1 (AlkB homologue 1)."; RL Biochem. J. 452:509-518(2013). RN [10] RP MUTAGENESIS OF HIS-113; CYS-118; CYS-129; HIS-134; HIS-303; CYS-304; RP CYS-371 AND HIS-372. RX PubMed=25459764; DOI=10.1016/j.jmgm.2014.10.013; RA Silvestrov P., Mueller T.A., Clark K.N., Hausinger R.P., Cisneros G.A.; RT "Homology modeling, molecular dynamics, and site-directed mutagenesis study RT of AlkB human homolog 1 (ALKBH1)."; RL J. Mol. Graph. Model. 54:123-130(2014). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 231-HIS--ASP-233. RX PubMed=27745969; DOI=10.1016/j.cell.2016.09.038; RA Liu F., Clark W., Luo G., Wang X., Fu Y., Wei J., Wang X., Hao Z., Dai Q., RA Zheng G., Ma H., Han D., Evans M., Klungland A., Pan T., He C.; RT "ALKBH1-mediated tRNA demethylation regulates translation."; RL Cell 167:816-828(2016). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-233 AND ARG-338. RX PubMed=27497299; DOI=10.15252/embj.201694885; RA Haag S., Sloan K.E., Ranjan N., Warda A.S., Kretschmer J., Blessing C., RA Huebner B., Seikowski J., Dennerlein S., Rehling P., Rodnina M.V., RA Hoebartner C., Bohnsack M.T.; RT "NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon RT recognition in mitochondrial translation."; RL EMBO J. 35:2104-2119(2016). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30392959; DOI=10.1016/j.cell.2018.10.006; RA Xie Q., Wu T.P., Gimple R.C., Li Z., Prager B.C., Wu Q., Yu Y., Wang P., RA Wang Y., Gorkin D.U., Zhang C., Dowiak A.V., Lin K., Zeng C., Sui Y., RA Kim L.J.Y., Miller T.E., Jiang L., Lee C.H., Huang Z., Fang X., Zhai K., RA Mack S.C., Sander M., Bao S., Kerstetter-Fogle A.E., Sloan A.E., Xiao A.Z., RA Rich J.N.; RT "N6-methyladenine DNA modification in glioblastoma."; RL Cell 175:1228-1243(2018). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF ASP-233. RX PubMed=30017583; DOI=10.1016/j.molcel.2018.06.015; RA Xiao C.L., Zhu S., He M., Chen D., Zhang Q., Chen Y., Yu G., Liu J., RA Xie S.Q., Luo F., Liang Z., Wang D.P., Bo X.C., Gu X.F., Wang K., Yan G.R.; RT "N6-methyladenine DNA modification in the human genome."; RL Mol. Cell 71:306-318(2018). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-233. RX PubMed=31188562; DOI=10.1021/acschembio.8b01001; RA Ma C.J., Ding J.H., Ye T.T., Yuan B.F., Feng Y.Q.; RT "AlkB homologue 1 demethylates N3-methylcytidine in mRNA of mammals."; RL ACS Chem. Biol. 14:1418-1425(2019). CC -!- FUNCTION: Dioxygenase that acts as on nucleic acids, such as DNA and CC tRNA (PubMed:18603530, PubMed:27745969, PubMed:27497299). Requires CC molecular oxygen, alpha-ketoglutarate and iron (PubMed:18603530, CC PubMed:27497299). A number of activities have been described for this CC dioxygenase, but recent results suggest that it mainly acts as on tRNAs CC and mediates their demethylation or oxidation depending on the context CC and subcellular compartment (PubMed:27745969, PubMed:27497299). Mainly CC acts as a tRNA demethylase by removing N(1)-methyladenine from various CC tRNAs, with a preference for N(1)-methyladenine at position 58 (m1A58) CC present on a stem loop structure of tRNAs (PubMed:27745969). Acts as a CC regulator of translation initiation and elongation in response to CC glucose deprivation: regulates both translation initiation, by CC mediating demethylation of tRNA(Met), and translation elongation, N(1)- CC methyladenine-containing tRNAs being preferentially recruited to CC polysomes to promote translation elongation (PubMed:27745969). In CC mitochondrion, specifically interacts with mt-tRNA(Met) and mediates CC oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5- CC formylcytosine (f(5)c) at this position (PubMed:27497299). mt-tRNA(Met) CC containing the f(5)c modification at the wobble position enables CC recognition of the AUA codon in addition to the AUG codon, expanding CC codon recognition in mitochondrial translation (PubMed:27497299). CC Specifically demethylates DNA methylated on the 6th position of adenine CC (N(6)-methyladenosine) DNA (PubMed:30392959, PubMed:30017583). N(6)- CC methyladenosine (m6A) DNA is present at some L1 elements in embryonic CC stem cells and probably promotes their silencing (By similarity). CC Demethylates mRNAs containing N(3)-methylcytidine modification CC (PubMed:31188562). Also able to repair alkylated single-stranded DNA by CC oxidative demethylation, but with low activity (PubMed:18603530). Also CC has DNA lyase activity and introduces double-stranded breaks at abasic CC sites: cleaves both single-stranded DNA and double-stranded DNA at CC abasic sites, with the greatest activity towards double-stranded DNA CC with two abasic sites (PubMed:19959401). DNA lyase activity does not CC require alpha-ketboglutarate and iron and leads to the formation of an CC irreversible covalent protein-DNA adduct with the 5' DNA product CC (PubMed:19959401, PubMed:23577621). DNA lyase activity is not required CC during base excision repair and class switch recombination of the CC immunoglobulin heavy chain during B lymphocyte activation. May play a CC role in placental trophoblast lineage differentiation (By similarity). CC {ECO:0000250|UniProtKB:P0CB42, ECO:0000269|PubMed:18603530, CC ECO:0000269|PubMed:19959401, ECO:0000269|PubMed:23577621, CC ECO:0000269|PubMed:27497299, ECO:0000269|PubMed:27745969, CC ECO:0000269|PubMed:30017583, ECO:0000269|PubMed:30392959, CC ECO:0000269|PubMed:31188562}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'- CC deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- CC dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-monophospho- CC 2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA- CC COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695, CC ChEBI:CHEBI:167181; EC=4.2.99.18; CC Evidence={ECO:0000305|PubMed:19959401}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + a methylated nucleobase within DNA + O2 = a CC nucleobase within DNA + CO2 + formaldehyde + succinate; CC Xref=Rhea:RHEA:30299, Rhea:RHEA-COMP:12192, Rhea:RHEA-COMP:12193, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:32875, CC ChEBI:CHEBI:64428; EC=1.14.11.33; CC Evidence={ECO:0000305|PubMed:18603530}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(6)-methyl-2'-deoxyadenosine in DNA + O2 CC = a 2'-deoxyadenosine in DNA + CO2 + formaldehyde + succinate; CC Xref=Rhea:RHEA:49524, Rhea:RHEA-COMP:12418, Rhea:RHEA-COMP:12419, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:90615, CC ChEBI:CHEBI:90616; EC=1.14.11.51; CC Evidence={ECO:0000269|PubMed:30017583, ECO:0000269|PubMed:30392959}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(1)-methyladenosine in tRNA + O2 = an CC adenosine in tRNA + CO2 + formaldehyde + succinate; CC Xref=Rhea:RHEA:54576, Rhea:RHEA-COMP:10242, Rhea:RHEA-COMP:12312, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74411, CC ChEBI:CHEBI:74491; Evidence={ECO:0000269|PubMed:27745969}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 2-oxoglutarate + 5-methylcytidine(34) in mitochondrial CC tRNA(Met) + 2 O2 = 5-formylcytidine(34) in mitochondrial tRNA(Met) + CC 2 CO2 + H2O + 2 succinate; Xref=Rhea:RHEA:54144, Rhea:RHEA- CC COMP:13808, Rhea:RHEA-COMP:13809, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:74483, ChEBI:CHEBI:138075; CC Evidence={ECO:0000269|PubMed:27497299}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(3)-methylcytidine in mRNA + O2 = a CC cytidine in mRNA + CO2 + formaldehyde + succinate; CC Xref=Rhea:RHEA:60920, Rhea:RHEA-COMP:15145, Rhea:RHEA-COMP:15713, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74894, CC ChEBI:CHEBI:82748; Evidence={ECO:0000269|PubMed:31188562}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60921; CC Evidence={ECO:0000269|PubMed:31188562}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00805, ECO:0000269|PubMed:18603530, CC ECO:0000269|PubMed:30017583}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE- CC ProRule:PRU00805}; CC -!- SUBUNIT: Monomer (PubMed:19959401). Interacts with DNAJB6 (By CC similarity). {ECO:0000250|UniProtKB:P0CB42, CC ECO:0000269|PubMed:19959401}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22961808}. CC Mitochondrion {ECO:0000269|PubMed:17979886, CC ECO:0000269|PubMed:18603530, ECO:0000269|PubMed:27497299}. Note=Mainly CC localizes in euchromatin, largely excluded from heterochromatin and CC nucleoli (By similarity). {ECO:0000250|UniProtKB:P0CB42}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:17979886, CC ECO:0000269|PubMed:18603530}. CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}. CC -!- CAUTION: The DNA N6-methyl adenine demethylase activity is subject to CC discussion. According to a report, biochemical assays do not reveal CC clear DNA N6-methyl adenine demethylase activity in vivo CC (PubMed:27745969). According to another study, has clear DNA N6-methyl CC adenine demethylase activity (PubMed:30017583). CC {ECO:0000269|PubMed:27745969, ECO:0000269|PubMed:30017583}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA63047.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X91992; CAA63047.1; ALT_FRAME; mRNA. DR EMBL; AC008044; AAF01478.1; -; Genomic_DNA. DR EMBL; BC025787; AAH25787.1; -; mRNA. DR CCDS; CCDS32127.1; -. DR PIR; S64736; S64736. DR RefSeq; NP_006011.2; NM_006020.2. DR PDB; 6IE2; X-ray; 2.80 A; A/B/C/D/E/F/G/H=1-389. DR PDB; 6IE3; X-ray; 1.97 A; A=1-389. DR PDBsum; 6IE2; -. DR PDBsum; 6IE3; -. DR AlphaFoldDB; Q13686; -. DR SMR; Q13686; -. DR BioGRID; 114372; 6. DR IntAct; Q13686; 1. DR STRING; 9606.ENSP00000216489; -. DR BindingDB; Q13686; -. DR ChEMBL; CHEMBL5169151; -. DR GlyGen; Q13686; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13686; -. DR PhosphoSitePlus; Q13686; -. DR SwissPalm; Q13686; -. DR BioMuta; ALKBH1; -. DR EPD; Q13686; -. DR jPOST; Q13686; -. DR MassIVE; Q13686; -. DR MaxQB; Q13686; -. DR PaxDb; 9606-ENSP00000216489; -. DR PeptideAtlas; Q13686; -. DR ProteomicsDB; 59661; -. DR Pumba; Q13686; -. DR Antibodypedia; 26095; 303 antibodies from 32 providers. DR DNASU; 8846; -. DR Ensembl; ENST00000216489.8; ENSP00000216489.3; ENSG00000100601.10. DR GeneID; 8846; -. DR KEGG; hsa:8846; -. DR MANE-Select; ENST00000216489.8; ENSP00000216489.3; NM_006020.3; NP_006011.2. DR UCSC; uc001xuc.2; human. DR AGR; HGNC:17911; -. DR DisGeNET; 8846; -. DR GeneCards; ALKBH1; -. DR HGNC; HGNC:17911; ALKBH1. DR HPA; ENSG00000100601; Low tissue specificity. DR MIM; 605345; gene. DR neXtProt; NX_Q13686; -. DR OpenTargets; ENSG00000100601; -. DR PharmGKB; PA134906996; -. DR VEuPathDB; HostDB:ENSG00000100601; -. DR eggNOG; KOG2731; Eukaryota. DR GeneTree; ENSGT00390000004599; -. DR HOGENOM; CLU_029471_2_1_1; -. DR InParanoid; Q13686; -. DR OMA; YKRRDPP; -. DR OrthoDB; 47845at2759; -. DR PhylomeDB; Q13686; -. DR TreeFam; TF314609; -. DR BRENDA; 1.14.11.51; 2681. DR PathwayCommons; Q13686; -. DR SignaLink; Q13686; -. DR BioGRID-ORCS; 8846; 12 hits in 1160 CRISPR screens. DR ChiTaRS; ALKBH1; human. DR GenomeRNAi; 8846; -. DR Pharos; Q13686; Tbio. DR PRO; PR:Q13686; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q13686; Protein. DR Bgee; ENSG00000100601; Expressed in oocyte and 201 other cell types or tissues. DR ExpressionAtlas; Q13686; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0000791; C:euchromatin; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:UniProtKB. DR GO; GO:0042056; F:chemoattractant activity; IEA:Ensembl. DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:UniProtKB. DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB. DR GO; GO:0070579; F:methylcytosine dioxygenase activity; IDA:UniProtKB. DR GO; GO:0035516; F:oxidative DNA demethylase activity; IDA:UniProtKB. DR GO; GO:0035515; F:oxidative RNA demethylase activity; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB. DR GO; GO:1990984; F:tRNA demethylase activity; IDA:UniProtKB. DR GO; GO:0048589; P:developmental growth; IEA:Ensembl. DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IDA:UniProtKB. DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl. DR GO; GO:0070989; P:oxidative demethylation; IDA:UniProtKB. DR GO; GO:0035513; P:oxidative RNA demethylation; IDA:UniProtKB. DR GO; GO:0035552; P:oxidative single-stranded DNA demethylation; IBA:GO_Central. DR GO; GO:0001890; P:placenta development; IEA:Ensembl. DR GO; GO:0070129; P:regulation of mitochondrial translation; IMP:UniProtKB. DR GO; GO:0006448; P:regulation of translational elongation; IMP:UniProtKB. DR GO; GO:0006446; P:regulation of translational initiation; IMP:UniProtKB. DR GO; GO:0042245; P:RNA repair; IDA:UniProtKB. DR GO; GO:1990983; P:tRNA demethylation; IDA:UniProtKB. DR GO; GO:0002101; P:tRNA wobble cytosine modification; IDA:UniProtKB. DR Gene3D; 2.60.120.590; Alpha-ketoglutarate-dependent dioxygenase AlkB-like; 1. DR InterPro; IPR004574; Alkb. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase. DR NCBIfam; TIGR00568; alkb; 1. DR PANTHER; PTHR16557; ALKYLATED DNA REPAIR PROTEIN ALKB-RELATED; 1. DR PANTHER; PTHR16557:SF2; NUCLEIC ACID DIOXYGENASE ALKBH1; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR Genevisible; Q13686; HS. PE 1: Evidence at protein level; KW 3D-structure; Dioxygenase; DNA damage; DNA repair; Iron; Lyase; KW Metal-binding; Mitochondrion; Multifunctional enzyme; Nucleus; KW Oxidoreductase; Reference proteome; RNA repair; Translation regulation. FT CHAIN 1..389 FT /note="Nucleic acid dioxygenase ALKBH1" FT /id="PRO_0000066668" FT DOMAIN 208..347 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT REGION 86..389 FT /note="tRNA-binding" FT /evidence="ECO:0000305|PubMed:27745969" FT BINDING 144 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q6NS38" FT BINDING 175..177 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q6NS38" FT BINDING 220..222 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q96Q83" FT BINDING 231 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000305|PubMed:19959401, ECO:0000305|PubMed:27745969" FT BINDING 233 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000305|PubMed:19959401, ECO:0000305|PubMed:27497299, FT ECO:0000305|PubMed:27745969, ECO:0000305|PubMed:31188562" FT BINDING 233 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q6NS38" FT BINDING 287 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT BINDING 338..344 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q96Q83" FT SITE 133 FT /note="Primary catalytic residue forming the imine linkage FT with DNA" FT /evidence="ECO:0000269|PubMed:23577621" FT SITE 133 FT /note="Secondary catalytic residue forming the imine FT linkage with DNA" FT /evidence="ECO:0000269|PubMed:23577621" FT VARIANT 135 FT /note="M -> I (in dbSNP:rs17825440)" FT /id="VAR_048221" FT VARIANT 324 FT /note="M -> L (in dbSNP:rs6494)" FT /id="VAR_048222" FT MUTAGEN 3 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 25 FT /note="K->A: Moderate decrease in DNA lyase activity. FT Reduced DNA lyase activity; when associated with A-133." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 55 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 61 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 64 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 87 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 94 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 113 FT /note="H->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 116 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 118 FT /note="C->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 120 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 125 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 129 FT /note="C->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 133 FT /note="K->A: Reduced DNA lyase activity. Slightly more FT reduced DNA lyase activity; when associated with A-25. FT Strongly reduced activity; when associated with A-154." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 134 FT /note="H->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 137 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 148 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 154 FT /note="K->A: Does not affect DNA lyase activity. Strongly FT reduced activity; when associated with A-133." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 158 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 167 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 182 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 183 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 218 FT /note="I->L: Reduces Fe2OG dioxygenase activity by 50%." FT /evidence="ECO:0000269|PubMed:18603530" FT MUTAGEN 231..233 FT /note="HVD->AVA: Loss of catalytic activity. Abolishes FT ability to regulate translation in respose to glucose FT deprivation." FT /evidence="ECO:0000269|PubMed:27745969" FT MUTAGEN 231 FT /note="H->A: Near loss of Fe2OG dioxygenase activity. No FT effect on DNA lyase activity." FT /evidence="ECO:0000269|PubMed:18603530, FT ECO:0000269|PubMed:19959401" FT MUTAGEN 233 FT /note="D->A: Loss of Fe2OG dioxygenase activity. No effect FT on DNA lyase activity. Abolishes ability to mediate FT oxidation of mt-tRNA(Met) methylated at cytosine(34) to FT form 5-formylcytosine (f(5)c). Abolished DNAN6-methyl FT adenine demethylase activity." FT /evidence="ECO:0000269|PubMed:18603530, FT ECO:0000269|PubMed:19959401, ECO:0000269|PubMed:27497299, FT ECO:0000269|PubMed:30017583, ECO:0000269|PubMed:31188562" FT MUTAGEN 241 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 287 FT /note="H->A: Loss of Fe2OG dioxygenase activity. No effect FT on DNA lyase activity." FT /evidence="ECO:0000269|PubMed:18603530, FT ECO:0000269|PubMed:19959401" FT MUTAGEN 303 FT /note="H->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 304 FT /note="C->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 335 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 338 FT /note="R->A: Reduced Fe2OG dioxygenase activity. Abolishes FT ability to mediate oxidation of mt-tRNA(Met) methylated at FT cytosine(34) to form 5-formylcytosine (f(5)c)." FT /evidence="ECO:0000269|PubMed:18603530, FT ECO:0000269|PubMed:27497299" FT MUTAGEN 344 FT /note="R->A: Reduced Fe2OG dioxygenase activity." FT /evidence="ECO:0000269|PubMed:18603530" FT MUTAGEN 362 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT MUTAGEN 371 FT /note="C->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 372 FT /note="H->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:25459764" FT MUTAGEN 381 FT /note="K->A: Does not affect DNA lyase activity." FT /evidence="ECO:0000269|PubMed:23577621" FT CONFLICT 133 FT /note="K -> T (in Ref. 1; CAA63047)" FT /evidence="ECO:0000305" FT CONFLICT 266..267 FT /note="TA -> PP (in Ref. 1; CAA63047)" FT /evidence="ECO:0000305" FT CONFLICT 388 FT /note="D -> H (in Ref. 3; AAH25787)" FT /evidence="ECO:0000305" FT HELIX 22..32 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 57..60 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 69..71 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 74..80 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 85..87 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 99..102 FT /evidence="ECO:0007829|PDB:6IE3" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 111..120 FT /evidence="ECO:0007829|PDB:6IE3" FT TURN 121..123 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 130..133 FT /evidence="ECO:0007829|PDB:6IE2" FT HELIX 137..140 FT /evidence="ECO:0007829|PDB:6IE2" FT HELIX 143..152 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 164..167 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 170..175 FT /evidence="ECO:0007829|PDB:6IE3" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 186..189 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 194..206 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 216..223 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 228..231 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 239..241 FT /evidence="ECO:0007829|PDB:6IE2" FT STRAND 243..250 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 252..256 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 266..270 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 275..278 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 280..284 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 287..292 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:6IE2" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:6IE3" FT HELIX 324..334 FT /evidence="ECO:0007829|PDB:6IE3" FT STRAND 337..344 FT /evidence="ECO:0007829|PDB:6IE3" SQ SEQUENCE 389 AA; 43832 MW; 539C4CE41D2D8AEC CRC64; MGKMAAAVGS VATLATEPGE DAFRKLFRFY RQSRPGTADL EGVIDFSAAH AARGKGPGAQ KVIKSQLNVS SVSEQNAYRA GLQPVSKWQA YGLKGYPGFI FIPNPFLPGY QWHWVKQCLK LYSQKPNVCN LDKHMSKEET QDLWEQSKEF LRYKEATKRR PRSLLEKLRW VTVGYHYNWD SKKYSADHYT PFPSDLGFLS EQVAAACGFE DFRAEAGILN YYRLDSTLGI HVDRSELDHS KPLLSFSFGQ SAIFLLGGLQ RDEAPTAMFM HSGDIMIMSG FSRLLNHAVP RVLPNPEGEG LPHCLEAPLP AVLPRDSMVE PCSMEDWQVC ASYLKTARVN MTVRQVLATD QNFPLEPIED EKRDISTEGF CHLDDQNSEV KRARINPDS //