ALKB1_HUMAN
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 03-AUG-2022, entry version 171.
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},
GN ABH1 {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;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805,
CC ECO:0000269|PubMed:18603530, 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};
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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; 4.
DR IntAct; Q13686; 1.
DR STRING; 9606.ENSP00000216489; -.
DR GlyGen; Q13686; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13686; -.
DR PhosphoSitePlus; Q13686; -.
DR BioMuta; ALKBH1; -.
DR EPD; Q13686; -.
DR jPOST; Q13686; -.
DR MassIVE; Q13686; -.
DR MaxQB; Q13686; -.
DR PaxDb; Q13686; -.
DR PeptideAtlas; Q13686; -.
DR PRIDE; Q13686; -.
DR ProteomicsDB; 59661; -.
DR Antibodypedia; 26095; 264 antibodies from 31 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 CTD; 8846; -.
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; WDTKKYS; -.
DR OrthoDB; 1045321at2759; -.
DR PhylomeDB; Q13686; -.
DR TreeFam; TF314609; -.
DR BRENDA; 1.14.11.51; 2681.
DR PathwayCommons; Q13686; -.
DR SignaLink; Q13686; -.
DR BioGRID-ORCS; 8846; 11 hits in 1080 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 199 other tissues.
DR ExpressionAtlas; Q13686; baseline and differential.
DR Genevisible; Q13686; HS.
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; -; 1.
DR InterPro; IPR004574; Alkb.
DR InterPro; IPR027450; AlkB-like.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR PANTHER; PTHR16557; PTHR16557; 1.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
DR TIGRFAMs; TIGR00568; alkb; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
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 DNA N6-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
