ALKB3_HUMAN
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 03-AUG-2022, entry version 172.
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 {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=8.40 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/";
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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 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; Q96Q83; -.
DR PeptideAtlas; Q96Q83; -.
DR PRIDE; Q96Q83; -.
DR ProteomicsDB; 77836; -. [Q96Q83-1]
DR ProteomicsDB; 77837; -. [Q96Q83-2]
DR Antibodypedia; 1876; 262 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 CTD; 221120; -.
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; LQDIPWG; -.
DR OrthoDB; 1494495at2759; -.
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 1085 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 150 other tissues.
DR ExpressionAtlas; Q96Q83; baseline and differential.
DR Genevisible; Q96Q83; HS.
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; -; 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; PTHR31212; 1.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
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
