ID ALKB3_HUMAN Reviewed; 286 AA. AC Q96Q83; A6NDJ1; Q3SYI0; Q6NX57; Q96BU8; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 {ECO:0000305}; DE EC=1.14.11.33 {ECO:0000269|PubMed:12486230, ECO:0000269|PubMed:16174769, ECO:0000269|PubMed:16858410, ECO:0000269|PubMed:20714506, ECO:0000269|PubMed:22055184}; DE EC=1.14.11.54 {ECO:0000269|PubMed:22055184, ECO:0000305|PubMed:26863196}; DE AltName: Full=Alkylated DNA repair protein alkB homolog 3 {ECO:0000303|PubMed:12594517}; DE Short=hABH3 {ECO:0000303|PubMed:12594517}; DE AltName: Full=DEPC-1 {ECO:0000303|Ref.1}; DE AltName: Full=Prostate cancer antigen 1 {ECO:0000303|Ref.1}; GN Name=ALKBH3 {ECO:0000312|HGNC:HGNC:30141}; GN Synonyms=ABH3 {ECO:0000303|PubMed:12594517}, DEPC1 GN {ECO:0000303|Ref.1}; 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] (ISOFORM 1). RC TISSUE=Fetal thymus, and Prostatic carcinoma; RA Tsujikawa K., Konishi N., Ono Y., Ichijou T., Sakamoto K., Yamamoto H.; RT "Homo sapiens mRNA expressed in prostate cancer and thymus."; RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-164 AND GLU-228. RG NIEHS SNPs program; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP GLU-228. RC TISSUE=Lung, and PNS; 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 [6] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=12486230; DOI=10.1073/pnas.262589799; RA Duncan T., Trewick S.C., Koivisto P., Bates P.A., Lindahl T., Sedgwick B.; RT "Reversal of DNA alkylation damage by two human dioxygenases."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16660-16665(2002). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12594517; DOI=10.1038/nature01363; RA Aas P.A., Otterlei M., Falnes P.O., Vaagboe C.B., Skorpen F., Akbari M., RA Sundheim O., Bjoeraas M., Slupphaug G., Seeberg E., Krokan H.E.; RT "Human and bacterial oxidative demethylases repair alkylation damage in RT both RNA and DNA."; RL Nature 421:859-863(2003). RN [8] RP FUNCTIONC, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS RP OF ASP-193 AND HIS-257, AND TISSUE SPECIFICITY. RX PubMed=16174769; DOI=10.1074/jbc.m509881200; RA Lee D.-H., Jin S.-G., Cai S., Chen Y., Pfeifer G.P., O'Connor T.R.; RT "Repair of methylation damage in DNA and RNA by mammalian AlkB RT homologues."; RL J. Biol. Chem. 280:39448-39459(2005). RN [9] 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 [10] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 122-ARG--ASP-124. RX PubMed=20714506; DOI=10.1039/c005148a; RA Chen B., Liu H., Sun X., Yang C.G.; RT "Mechanistic insight into the recognition of single-stranded and double- RT stranded DNA substrates by ABH2 and ABH3."; RL Mol. Biosyst. 6:2143-2149(2010). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ASCC3, AND MUTAGENESIS OF RP HIS-257. RX PubMed=22055184; DOI=10.1016/j.molcel.2011.08.039; RA Dango S., Mosammaparast N., Sowa M.E., Xiong L.J., Wu F., Park K., RA Rubin M., Gygi S., Harper J.W., Shi Y.; RT "DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA RT alkylation repair and cancer cell proliferation."; RL Mol. Cell 44:373-384(2011). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25797601; DOI=10.1016/j.dnarep.2015.02.021; RA Zdzalik D., Domanska A., Prorok P., Kosicki K., van den Born E., RA Falnes P.O., Rizzo C.J., Guengerich F.P., Tudek B.; RT "Differential repair of etheno-DNA adducts by bacterial and human AlkB RT proteins."; RL DNA Repair 30:1-10(2015). RN [13] RP FUNCTION, AND MUTAGENESIS OF ASP-193. RX PubMed=26863196; DOI=10.1038/nature16998; RA Dominissini D., Nachtergaele S., Moshitch-Moshkovitz S., Peer E., Kol N., RA Ben-Haim M.S., Dai Q., Di Segni A., Salmon-Divon M., Clark W.C., Zheng G., RA Pan T., Solomon O., Eyal E., Hershkovitz V., Han D., Dore L.C., RA Amariglio N., Rechavi G., He C.; RT "The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA."; RL Nature 530:441-446(2016). RN [14] RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH OTUD4; USP7 AND USP9X. RX PubMed=25944111; DOI=10.15252/embj.201490497; RA Zhao Y., Majid M.C., Soll J.M., Brickner J.R., Dango S., Mosammaparast N.; RT "Noncanonical regulation of alkylation damage resistance by the OTUD4 RT deubiquitinase."; RL EMBO J. 34:1687-1703(2015). RN [15] RP FUNCTION. RX PubMed=26863410; DOI=10.1038/nchembio.2040; RA Li X., Xiong X., Wang K., Wang L., Shu X., Ma S., Yi C.; RT "Transcriptome-wide mapping reveals reversible and dynamic N(1)- RT methyladenosine methylome."; RL Nat. Chem. Biol. 12:311-316(2016). RN [16] RP INTERACTION WITH ASCC3 AND THE ASCC COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=29144457; DOI=10.1038/nature24484; RA Brickner J.R., Soll J.M., Lombardi P.M., Vaagboe C.B., Mudge M.C., RA Oyeniran C., Rabe R., Jackson J., Sullender M.E., Blazosky E., Byrum A.K., RA Zhao Y., Corbett M.A., Gecz J., Field M., Vindigni A., Slupphaug G., RA Wolberger C., Mosammaparast N.; RT "A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA RT dealkylation repair."; RL Nature 551:389-393(2017). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 70-286 IN COMPLEX WITH RP ALPHA-KETOGLUTARATE AND IRON, COFACTOR, CATALYTIC ACTIVITY, FUNCTION, RP IDENTIFICATION BY MASS SPECTROMETRY, HYDROXYLATION AT LEU-177, OXIDATION AT RP LEU-177, AND MUTAGENESIS OF ARG-122; GLU-123; ARG-131; LEU-177; ASN-179; RP TYR-181; ASP-189; HIS-191; ASP-193; HIS-257; ARG-269; ASN-271 AND ARG-275. RX PubMed=16858410; DOI=10.1038/sj.emboj.7601219; RA Sundheim O., Vaagboe C.B., Bjoeraas M., Sousa M.M.L., Talstad V., Aas P.A., RA Drabloes F., Krokan H.E., Tainer J.A., Slupphaug G.; RT "Human ABH3 structure and key residues for oxidative demethylation to RT reverse DNA/RNA damage."; RL EMBO J. 25:3389-3397(2006). CC -!- FUNCTION: Dioxygenase that mediates demethylation of DNA and RNA CC containing 1-methyladenosine (m1A) (PubMed:12486230, PubMed:12594517, CC PubMed:16174769, PubMed:26863196, PubMed:26863410). Repairs alkylated CC DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by CC oxidative demethylation (PubMed:12486230, PubMed:12594517, CC PubMed:16174769, PubMed:25944111). Has a strong preference for single- CC stranded DNA (PubMed:12486230, PubMed:12594517, PubMed:16174769, CC PubMed:20714506). Able to process alkylated m3C within double-stranded CC regions via its interaction with ASCC3, which promotes DNA unwinding to CC generate single-stranded substrate needed for ALKBH3 (PubMed:22055184). CC Can repair exocyclic 3,N4-ethenocytosine adducs in single-stranded DNA CC (PubMed:25797601). Also acts on RNA (PubMed:12594517, PubMed:16174769, CC PubMed:26863196, PubMed:26863410, PubMed:16858410). Demethylates N(1)- CC methyladenosine (m1A) RNA, an epigenetic internal modification of CC messenger RNAs (mRNAs) highly enriched within 5'-untranslated regions CC (UTRs) and in the vicinity of start codons (PubMed:26863196, CC PubMed:26863410). Requires molecular oxygen, alpha-ketoglutarate and CC iron (PubMed:22055184, PubMed:16858410). {ECO:0000269|PubMed:12486230, CC ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:16174769, CC ECO:0000269|PubMed:16858410, ECO:0000269|PubMed:22055184, CC ECO:0000269|PubMed:25797601, ECO:0000269|PubMed:25944111, CC ECO:0000269|PubMed:26863196, ECO:0000269|PubMed:26863410}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(1)-methyladenosine in mRNA + O2 = an CC adenosine in mRNA + CO2 + formaldehyde + succinate; CC Xref=Rhea:RHEA:49516, Rhea:RHEA-COMP:12414, Rhea:RHEA-COMP:12415, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74411, CC ChEBI:CHEBI:74491; EC=1.14.11.54; CC Evidence={ECO:0000305|PubMed:26863196}; 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:0000269|PubMed:12486230, ECO:0000269|PubMed:16174769, CC ECO:0000269|PubMed:16858410, ECO:0000269|PubMed:20714506, CC ECO:0000269|PubMed:22055184}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30300; CC Evidence={ECO:0000305|PubMed:12486230, ECO:0000305|PubMed:16174769, CC ECO:0000305|PubMed:16858410, ECO:0000305|PubMed:20714506, CC ECO:0000305|PubMed:22055184}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(1)-methyl-2'-deoxyadenosine in single- CC stranded DNA + O2 = a 2'-deoxyadenosine in single-stranded DNA + CO2 CC + formaldehyde + H(+) + succinate; Xref=Rhea:RHEA:70447, Rhea:RHEA- CC COMP:17895, Rhea:RHEA-COMP:17896, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:90615, CC ChEBI:CHEBI:139096; Evidence={ECO:0000269|PubMed:12486230, CC ECO:0000269|PubMed:16174769, ECO:0000269|PubMed:16858410, CC ECO:0000269|PubMed:20714506}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70448; CC Evidence={ECO:0000305|PubMed:12486230, ECO:0000305|PubMed:16174769, CC ECO:0000305|PubMed:16858410, ECO:0000305|PubMed:20714506}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(3)-methyl-2'-deoxycytidine in single- CC stranded DNA + O2 = a 2'-deoxycytidine in single-stranded DNA + CO2 + CC formaldehyde + H(+) + succinate; Xref=Rhea:RHEA:70435, Rhea:RHEA- CC COMP:12846, Rhea:RHEA-COMP:17894, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:85452, CC ChEBI:CHEBI:139075; Evidence={ECO:0000269|PubMed:12486230, CC ECO:0000269|PubMed:16174769, ECO:0000269|PubMed:22055184}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70436; CC Evidence={ECO:0000305|PubMed:12486230, ECO:0000305|PubMed:16174769, CC ECO:0000305|PubMed:22055184}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + a 3,N(4)-etheno-2'-deoxycytidine in single- CC stranded DNA + H2O + O2 = a 2'-deoxycytidine in single-stranded DNA + CC CO2 + glyoxal + succinate; Xref=Rhea:RHEA:70471, Rhea:RHEA- CC COMP:12846, Rhea:RHEA-COMP:17906, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:34779, ChEBI:CHEBI:85452, CC ChEBI:CHEBI:189585; Evidence={ECO:0000269|PubMed:25797601}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70472; CC Evidence={ECO:0000305|PubMed:25797601}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:16858410}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:16858410}; CC -!- ACTIVITY REGULATION: Activated by ascorbate. CC {ECO:0000269|PubMed:12486230}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=182 nM for N(1)-methyl-2'-deoxyadenosine in single-stranded DNA CC {ECO:0000269|PubMed:16174769}; CC KM=263 nM for N(1)-methyl-2'-deoxyadenosine in double-stranded DNA CC {ECO:0000269|PubMed:16174769}; CC KM=162 nM for N(3)-methyl-2'-deoxycytidine in single-stranded DNA CC {ECO:0000269|PubMed:16174769}; CC KM=8.4 nM for N(3)-methyl-2'-deoxycytidine in double-stranded DNA CC {ECO:0000269|PubMed:16174769}; CC -!- SUBUNIT: Interacts with the ASCC complex composed of ASCC1, ASCC2 and CC ASCC3 (PubMed:29144457, PubMed:22055184). Interacts directly with CC ASCC3, and is thereby recruited to the ASCC complex (PubMed:22055184, CC PubMed:29144457). Interacts with OTUD4; the interaction is direct CC (PubMed:25944111). Interacts with USP7 and USP9X (PubMed:25944111). CC {ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:25944111, CC ECO:0000269|PubMed:29144457}. CC -!- INTERACTION: CC Q96Q83; Q96MA6: AK8; NbExp=3; IntAct=EBI-6658697, EBI-8466265; CC Q96Q83; O76003: GLRX3; NbExp=3; IntAct=EBI-6658697, EBI-374781; CC Q96Q83; Q08379: GOLGA2; NbExp=5; IntAct=EBI-6658697, EBI-618309; CC Q96Q83; Q13422: IKZF1; NbExp=5; IntAct=EBI-6658697, EBI-745305; CC Q96Q83; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-6658697, EBI-739832; CC Q96Q83-2; P55212: CASP6; NbExp=3; IntAct=EBI-9089544, EBI-718729; CC Q96Q83-2; P13473-2: LAMP2; NbExp=3; IntAct=EBI-9089544, EBI-21591415; CC Q96Q83-2; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-9089544, EBI-5280197; CC Q96Q83-2; P62826: RAN; NbExp=3; IntAct=EBI-9089544, EBI-286642; CC Q96Q83-2; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-9089544, EBI-2623095; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12486230, CC ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:17979886, CC ECO:0000269|PubMed:29144457}. Cytoplasm {ECO:0000269|PubMed:12486230, CC ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:17979886}. CC Note=Colocalizes with ASCC2 and ASCC3 in nuclear foci when cells have CC been exposed to alkylating agents that cause DNA damage CC (PubMed:29144457). Predominantly localizes to the nucleus. CC {ECO:0000269|PubMed:12486230, ECO:0000269|PubMed:12594517, CC ECO:0000269|PubMed:17979886, ECO:0000269|PubMed:29144457}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96Q83-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96Q83-2; Sequence=VSP_019125, VSP_019126, VSP_019127; CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in heart, pancreas, skeletal CC muscle, thymus, testis, ovary, spleen, prostate, small intestine, CC peripheral blood leukocytes, urinary bladder and colon. CC {ECO:0000269|PubMed:12486230, ECO:0000269|PubMed:16174769, CC ECO:0000269|PubMed:17979886}. CC -!- PTM: Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination. OTUD4 CC promotes USP7 and USP9X-dependent deubiquitination of 'Lys-48'- CC polyubiquitinated ALKBH3 promoting the repair of alkylated DNA lesions. CC {ECO:0000269|PubMed:25944111}. CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH15155.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/depc1/"; 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; AB042029; BAB70508.1; -; mRNA. DR EMBL; DQ196343; ABA27096.1; -; Genomic_DNA. DR EMBL; AC087521; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68078.1; -; Genomic_DNA. DR EMBL; BC015155; AAH15155.1; ALT_INIT; mRNA. DR EMBL; BC103812; AAI03813.1; -; mRNA. DR EMBL; BC103813; AAI03814.1; -; mRNA. DR EMBL; BC103814; AAI03815.1; -; mRNA. DR EMBL; BC067257; AAH67257.1; -; mRNA. DR CCDS; CCDS7906.1; -. [Q96Q83-1] DR RefSeq; NP_631917.1; NM_139178.3. [Q96Q83-1] DR PDB; 2IUW; X-ray; 1.50 A; A=70-286. DR PDBsum; 2IUW; -. DR AlphaFoldDB; Q96Q83; -. DR SMR; Q96Q83; -. DR BioGRID; 128686; 55. DR IntAct; Q96Q83; 21. DR STRING; 9606.ENSP00000302232; -. DR BindingDB; Q96Q83; -. DR ChEMBL; CHEMBL3112376; -. DR DrugBank; DB00126; Ascorbic acid. DR GlyGen; Q96Q83; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96Q83; -. DR PhosphoSitePlus; Q96Q83; -. DR BioMuta; ALKBH3; -. DR DMDM; 74752087; -. DR EPD; Q96Q83; -. DR jPOST; Q96Q83; -. DR MassIVE; Q96Q83; -. DR MaxQB; Q96Q83; -. DR PaxDb; 9606-ENSP00000302232; -. DR PeptideAtlas; Q96Q83; -. DR ProteomicsDB; 77836; -. [Q96Q83-1] DR ProteomicsDB; 77837; -. [Q96Q83-2] DR Pumba; Q96Q83; -. DR Antibodypedia; 1876; 271 antibodies from 31 providers. DR DNASU; 221120; -. DR Ensembl; ENST00000302708.9; ENSP00000302232.4; ENSG00000166199.13. [Q96Q83-1] DR Ensembl; ENST00000530803.5; ENSP00000436788.1; ENSG00000166199.13. [Q96Q83-2] DR GeneID; 221120; -. DR KEGG; hsa:221120; -. DR MANE-Select; ENST00000302708.9; ENSP00000302232.4; NM_139178.4; NP_631917.1. DR UCSC; uc001mxs.3; human. [Q96Q83-1] DR AGR; HGNC:30141; -. DR DisGeNET; 221120; -. DR GeneCards; ALKBH3; -. DR HGNC; HGNC:30141; ALKBH3. DR HPA; ENSG00000166199; Low tissue specificity. DR MIM; 610603; gene. DR neXtProt; NX_Q96Q83; -. DR OpenTargets; ENSG00000166199; -. DR PharmGKB; PA143485293; -. DR VEuPathDB; HostDB:ENSG00000166199; -. DR eggNOG; ENOG502QW9E; Eukaryota. DR GeneTree; ENSGT00940000157226; -. DR HOGENOM; CLU_048788_2_1_1; -. DR InParanoid; Q96Q83; -. DR OMA; FEFHQPT; -. DR OrthoDB; 36492at2759; -. DR PhylomeDB; Q96Q83; -. DR TreeFam; TF331732; -. DR BRENDA; 1.14.11.33; 2681. DR BRENDA; 1.14.11.54; 2681. DR PathwayCommons; Q96Q83; -. DR Reactome; R-HSA-112126; ALKBH3 mediated reversal of alkylation damage. DR SignaLink; Q96Q83; -. DR BioGRID-ORCS; 221120; 18 hits in 1164 CRISPR screens. DR ChiTaRS; ALKBH3; human. DR EvolutionaryTrace; Q96Q83; -. DR GenomeRNAi; 221120; -. DR Pharos; Q96Q83; Tchem. DR PRO; PR:Q96Q83; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96Q83; Protein. DR Bgee; ENSG00000166199; Expressed in right uterine tube and 152 other cell types or tissues. DR ExpressionAtlas; Q96Q83; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0043734; F:DNA-N1-methyladenine dioxygenase activity; IDA:UniProtKB. DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW. DR GO; GO:1990930; F:mRNA N1-methyladenosine 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:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB. DR GO; GO:0035552; P:oxidative single-stranded DNA demethylation; IDA:UniProtKB. DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; IDA:UniProtKB. DR Gene3D; 2.60.120.590; Alpha-ketoglutarate-dependent dioxygenase AlkB-like; 1. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR032854; ALKBH3. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase. DR PANTHER; PTHR31212; ALPHA-KETOGLUTARATE-DEPENDENT DIOXYGENASE ALKB HOMOLOG 3; 1. DR PANTHER; PTHR31212:SF4; ALPHA-KETOGLUTARATE-DEPENDENT DIOXYGENASE ALKB HOMOLOG 3; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR Genevisible; Q96Q83; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Dioxygenase; DNA damage; KW DNA repair; Hydroxylation; Iron; Metal-binding; Nucleus; Oxidation; KW Oxidoreductase; Reference proteome; Ubl conjugation; Vitamin C. FT CHAIN 1..286 FT /note="Alpha-ketoglutarate-dependent dioxygenase alkB FT homolog 3" FT /id="PRO_0000239278" FT DOMAIN 172..278 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT REGION 21..45 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 22..37 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 115 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q6NS38" FT BINDING 141..143 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q6NS38" FT BINDING 179..181 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:16858410, FT ECO:0007744|PDB:2IUW" FT BINDING 191 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:16858410, ECO:0007744|PDB:2IUW" FT BINDING 193 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:16858410, ECO:0007744|PDB:2IUW" FT BINDING 194 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q6NS38" FT BINDING 257 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805, FT ECO:0000269|PubMed:16858410, ECO:0007744|PDB:2IUW" FT BINDING 269..275 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:16858410, FT ECO:0007744|PDB:2IUW" FT BINDING 275 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:16858410, FT ECO:0007744|PDB:2IUW" FT MOD_RES 177 FT /note="(4R)-5-hydroxyleucine; alternate" FT /evidence="ECO:0000269|PubMed:16858410" FT MOD_RES 177 FT /note="(4R)-5-oxoleucine; alternate" FT /evidence="ECO:0000269|PubMed:16858410" FT VAR_SEQ 73..74 FT /note="DR -> E (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019125" FT VAR_SEQ 125..172 FT /note="ITYQQPRLTAWYGELPYTYSRITMEPNPHWHPVLRTLKNRIEENTGHT -> FT SILQLTFKKSAPVSGTATAPQSCWYERPSPPHIPGPAILTRTRLWAP (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019126" FT VAR_SEQ 173..286 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019127" FT VARIANT 164 FT /note="R -> C (in dbSNP:rs2271815)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_026632" FT VARIANT 228 FT /note="D -> E (in dbSNP:rs1130290)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2" FT /id="VAR_026631" FT MUTAGEN 122..124 FT /note="RED->VGF: Acquires the capacity to efficiently FT repair N1-methyladenine adduct in dsDNA." FT /evidence="ECO:0000269|PubMed:20714506" FT MUTAGEN 122 FT /note="R->A: Decreases activity towards ssDNA by 25%. Loss FT of activity towards dsDNA." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 123 FT /note="E->A: Strongly increases activity towards dsDNA, FT possibly by facilitating access to the active site." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 131 FT /note="R->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 177 FT /note="L->A,N: Loss of activity against N1-methyladenine." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 177 FT /note="L->E,Q: Loss of activity." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 177 FT /note="L->I: Decreases activity against N1-methyladenine." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 177 FT /note="L->M: No effect." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 179 FT /note="N->A: Decreases activity by about 60%." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 181 FT /note="Y->A: Strong decrease of activity." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 189 FT /note="D->A: Strongly increases activity towards dsDNA, FT possibly by facilitating access to the active site." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 191 FT /note="H->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 193 FT /note="D->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:16174769, FT ECO:0000269|PubMed:26863196" FT MUTAGEN 257 FT /note="H->A: Decreases activity by about 65%." FT /evidence="ECO:0000269|PubMed:16174769, FT ECO:0000269|PubMed:22055184" FT MUTAGEN 269 FT /note="R->A: Strong decrease of activity." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 271 FT /note="N->A: No effect." FT /evidence="ECO:0000269|PubMed:16858410" FT MUTAGEN 275 FT /note="R->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:16858410" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 74..81 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 88..93 FT /evidence="ECO:0007829|PDB:2IUW" FT HELIX 99..112 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 119..124 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 130..137 FT /evidence="ECO:0007829|PDB:2IUW" FT HELIX 145..148 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 151..153 FT /evidence="ECO:0007829|PDB:2IUW" FT HELIX 156..169 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 175..181 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 188..191 FT /evidence="ECO:0007829|PDB:2IUW" FT HELIX 196..198 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 204..211 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 213..219 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 234..239 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 244..249 FT /evidence="ECO:0007829|PDB:2IUW" FT HELIX 251..254 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:2IUW" FT STRAND 269..275 FT /evidence="ECO:0007829|PDB:2IUW" SQ SEQUENCE 286 AA; 33375 MW; F6563635B1F217D7 CRC64; MEEKRRRARV QGAWAAPVKS QAIAQPATTA KSHLHQKPGQ TWKNKEHHLS DREFVFKEPQ QVVRRAPEPR VIDREGVYEI SLSPTGVSRV CLYPGFVDVK EADWILEQLC QDVPWKQRTG IREDITYQQP RLTAWYGELP YTYSRITMEP NPHWHPVLRT LKNRIEENTG HTFNSLLCNL YRNEKDSVDW HSDDEPSLGR CPIIASLSFG ATRTFEMRKK PPPEENGDYT YVERVKIPLD HGTLLIMEGA TQADWQHRVP KEYHSREPRV NLTFRTVYPD PRGAPW //