ALKB3_MOUSE
ID ALKB3_MOUSE Reviewed; 286 AA.
AC Q8K1E6;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 {ECO:0000305};
DE EC=1.14.11.33 {ECO:0000269|PubMed:16174769};
DE EC=1.14.11.54 {ECO:0000250|UniProtKB:Q96Q83};
DE AltName: Full=Alkylated DNA repair protein alkB homolog 3 {ECO:0000303|PubMed:16174769};
DE Short=mAbh3 {ECO:0000303|PubMed:16174769};
GN Name=Alkbh3 {ECO:0000312|MGI:MGI:1916363};
GN Synonyms=Abh3 {ECO:0000303|PubMed:16174769};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [2]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-193 AND HIS-257, AND
RP 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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16642038; DOI=10.1038/sj.emboj.7601109;
RA Ringvoll J., Nordstrand L.M., Vaagboe C.B., Talstad V., Reite K., Aas P.A.,
RA Lauritzen K.H., Liabakk N.B., Bjoerk A., Doughty R.W., Falnes P.O.,
RA Krokan H.E., Klungland A.;
RT "Repair deficient mice reveal mABH2 as the primary oxidative demethylase
RT for repairing 1meA and 3meC lesions in DNA.";
RL EMBO J. 25:2189-2198(2006).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=18519673; DOI=10.1158/0008-5472.can-08-0796;
RA Ringvoll J., Moen M.N., Nordstrand L.M., Meira L.B., Pang B., Bekkelund A.,
RA Dedon P.C., Bjelland S., Samson L.D., Falnes P.O., Klungland A.;
RT "AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian
RT DNA.";
RL Cancer Res. 68:4142-4149(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Dioxygenase that mediates demethylation of DNA and RNA
CC containing 1-methyladenosine (m1A) (By similarity). Repairs alkylated
CC DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by
CC oxidative demethylation (PubMed:16174769). Has a strong preference for
CC single-stranded DNA (PubMed:16174769). Able to process alkylated m3C
CC within double-stranded regions via its interaction with ASCC3, which
CC promotes DNA unwinding to generate single-stranded substrate needed for
CC ALKBH3. Can repair exocyclic 3,N4-ethenocytosine adducs in single-
CC stranded DNA. Also acts on RNA. Demethylates N(1)-methyladenosine (m1A)
CC RNA, an epigenetic internal modification of messenger RNAs (mRNAs)
CC highly enriched within 5'-untranslated regions (UTRs) and in the
CC vicinity of start codons. Requires molecular oxygen, alpha-
CC ketoglutarate and iron (By similarity). {ECO:0000250|UniProtKB:Q96Q83,
CC ECO:0000269|PubMed:16174769}.
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:0000250|UniProtKB:Q96Q83};
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:16174769};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30300;
CC Evidence={ECO:0000305|PubMed:16174769};
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:16174769};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70448;
CC Evidence={ECO:0000305|PubMed:16174769};
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:16174769};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70436;
CC Evidence={ECO:0000305|PubMed:16174769};
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:0000250|UniProtKB:Q96Q83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70472;
CC Evidence={ECO:0000250|UniProtKB:Q96Q83};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q96Q83};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q96Q83};
CC -!- ACTIVITY REGULATION: Activated by ascorbate.
CC {ECO:0000250|UniProtKB:Q96Q83}.
CC -!- SUBUNIT: Interacts with the ASCC complex composed of ASCC1, ASCC2 and
CC ASCC3. Interacts directly with ASCC3, and is thereby recruited to the
CC ASCC complex. Interacts with OTUD4; the interaction is direct.
CC Interacts with USP7 and USP9X. {ECO:0000250|UniProtKB:Q96Q83}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96Q83}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q96Q83}. Note=Colocalizes with ASCC2 and ASCC3
CC in nuclear foci when cells have been exposed to alkylating agents that
CC cause DNA damage. Predominantly localizes to the nucleus.
CC {ECO:0000250|UniProtKB:Q96Q83}.
CC -!- TISSUE SPECIFICITY: Detected in testis, kidney, liver and heart.
CC {ECO:0000269|PubMed:16174769}.
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:0000250|UniProtKB:Q96Q83}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype.
CC {ECO:0000269|PubMed:16642038, ECO:0000269|PubMed:18519673}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR EMBL; BC018196; AAH18196.1; -; mRNA.
DR CCDS; CCDS38184.1; -.
DR RefSeq; NP_081220.1; NM_026944.1.
DR RefSeq; XP_006500186.1; XM_006500123.3.
DR AlphaFoldDB; Q8K1E6; -.
DR SMR; Q8K1E6; -.
DR BioGRID; 213237; 4.
DR STRING; 10090.ENSMUSP00000106871; -.
DR iPTMnet; Q8K1E6; -.
DR PhosphoSitePlus; Q8K1E6; -.
DR EPD; Q8K1E6; -.
DR jPOST; Q8K1E6; -.
DR MaxQB; Q8K1E6; -.
DR PaxDb; Q8K1E6; -.
DR PeptideAtlas; Q8K1E6; -.
DR PRIDE; Q8K1E6; -.
DR ProteomicsDB; 296021; -.
DR Antibodypedia; 1876; 262 antibodies from 31 providers.
DR Ensembl; ENSMUST00000040005; ENSMUSP00000038721; ENSMUSG00000040174.
DR GeneID; 69113; -.
DR KEGG; mmu:69113; -.
DR UCSC; uc008lgn.1; mouse.
DR CTD; 221120; -.
DR MGI; MGI:1916363; Alkbh3.
DR VEuPathDB; HostDB:ENSMUSG00000040174; -.
DR eggNOG; ENOG502QW9E; Eukaryota.
DR GeneTree; ENSGT00940000157226; -.
DR HOGENOM; CLU_048788_2_1_1; -.
DR InParanoid; Q8K1E6; -.
DR OMA; LQDIPWG; -.
DR OrthoDB; 1494495at2759; -.
DR BRENDA; 1.14.11.54; 3474.
DR BioGRID-ORCS; 69113; 2 hits in 110 CRISPR screens.
DR ChiTaRS; Alkbh3; mouse.
DR PRO; PR:Q8K1E6; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K1E6; protein.
DR Bgee; ENSMUSG00000040174; Expressed in interventricular septum and 224 other tissues.
DR ExpressionAtlas; Q8K1E6; baseline and differential.
DR Genevisible; Q8K1E6; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:MGI.
DR GO; GO:0051747; F:cytosine C-5 DNA demethylase activity; IDA:MGI.
DR GO; GO:0043734; F:DNA-N1-methyladenine dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0008198; F:ferrous iron binding; ISS:UniProtKB.
DR GO; GO:1990930; F:mRNA N1-methyladenosine dioxygenase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0035552; P:oxidative single-stranded DNA demethylation; ISS:UniProtKB.
DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; ISO:MGI.
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 Cytoplasm; Dioxygenase; DNA damage; DNA repair; Hydroxylation; Iron;
KW Metal-binding; Nucleus; Oxidation; Oxidoreductase; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..286
FT /note="Alpha-ketoglutarate-dependent dioxygenase alkB
FT homolog 3"
FT /id="PRO_0000239279"
FT DOMAIN 172..278
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..46
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:0000250|UniProtKB:Q96Q83"
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 BINDING 193
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
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 BINDING 269..275
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q96Q83"
FT BINDING 275
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q96Q83"
FT MOD_RES 177
FT /note="(4R)-5-hydroxyleucine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96Q83"
FT MOD_RES 177
FT /note="(4R)-5-oxoleucine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96Q83"
FT MUTAGEN 193
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16174769"
FT MUTAGEN 257
FT /note="H->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:16174769"
SQ SEQUENCE 286 AA; 33061 MW; 2480D0D20A9893F4 CRC64;
MEDKRQRARV QGGWATPTKS QSATQPASPA RSRLSQTAGP AWRSKEQQQC DRQFVFKEPQ
LVVRAAPEPR VIDREGVYEI SLSPTGVSRV CLYPGFVDLK EADWILEQLC KDVPWKQRMG
IREDVTYPQP RLTAWYGELP YTYSRITMEP NPHWLPVLWT LKSRIEENTS HTFNSLLCNF
YRDEKDSVDW HSDDEPSLGS CPVIASLSFG ATRTFEMRKK PPPEENGDYT YVERVKIPLD
HGTLLIMEGA TQADWQHRVP KEYHSRQPRV NLTFRTVYPD PRGAPR
