ALKB3_RAT
ID ALKB3_RAT Reviewed; 295 AA.
AC Q5XIC8;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 {ECO:0000250|UniProtKB:Q96Q83};
DE EC=1.14.11.33 {ECO:0000250|UniProtKB:Q96Q83};
DE EC=1.14.11.54 {ECO:0000250|UniProtKB:Q96Q83};
DE AltName: Full=Alkylated DNA repair protein alkB homolog 3 {ECO:0000250|UniProtKB:Q96Q83};
GN Name=Alkbh3 {ECO:0000250|UniProtKB:Q96Q83};
GN Synonyms=Abh3 {ECO:0000250|UniProtKB:Q96Q83};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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).
CC -!- FUNCTION: Dioxygenase that mediates demethylation of DNA and RNA
CC containing 1-methyladenosine (m1A). Repairs alkylated DNA containing 1-
CC methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative
CC demethylation. Has a strong preference for single-stranded DNA. Able to
CC process alkylated m3C within double-stranded regions via its
CC interaction with ASCC3, which promotes DNA unwinding to generate
CC single-stranded substrate needed for ALKBH3. Can repair exocyclic 3,N4-
CC ethenocytosine adducs in single-stranded DNA. Also acts on RNA.
CC Demethylates N(1)-methyladenosine (m1A) RNA, an epigenetic internal
CC modification of messenger RNAs (mRNAs) highly enriched within 5'-
CC untranslated regions (UTRs) and in the vicinity of start codons.
CC Requires molecular oxygen, alpha-ketoglutarate and iron.
CC {ECO:0000250|UniProtKB:Q96Q83}.
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:0000250|UniProtKB:Q96Q83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30300;
CC Evidence={ECO:0000250|UniProtKB:Q96Q83};
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:0000250|UniProtKB:Q96Q83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70448;
CC Evidence={ECO:0000250|UniProtKB:Q96Q83};
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:0000250|UniProtKB:Q96Q83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70436;
CC Evidence={ECO:0000250|UniProtKB:Q96Q83};
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 -!- 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 -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR EMBL; BC083756; AAH83756.1; -; mRNA.
DR RefSeq; NP_001014202.1; NM_001014180.1.
DR RefSeq; XP_006234647.1; XM_006234585.3.
DR AlphaFoldDB; Q5XIC8; -.
DR SMR; Q5XIC8; -.
DR STRING; 10116.ENSRNOP00000030278; -.
DR PhosphoSitePlus; Q5XIC8; -.
DR PaxDb; Q5XIC8; -.
DR PRIDE; Q5XIC8; -.
DR Ensembl; ENSRNOT00000030784; ENSRNOP00000030278; ENSRNOG00000021678.
DR GeneID; 362169; -.
DR KEGG; rno:362169; -.
DR UCSC; RGD:1359731; rat.
DR CTD; 221120; -.
DR RGD; 1359731; Alkbh3.
DR eggNOG; ENOG502QW9E; Eukaryota.
DR GeneTree; ENSGT00940000157226; -.
DR HOGENOM; CLU_048788_2_1_1; -.
DR InParanoid; Q5XIC8; -.
DR OMA; LQDIPWG; -.
DR OrthoDB; 1494495at2759; -.
DR PhylomeDB; Q5XIC8; -.
DR TreeFam; TF331732; -.
DR PRO; PR:Q5XIC8; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000021678; Expressed in skeletal muscle tissue and 20 other tissues.
DR Genevisible; Q5XIC8; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; ISO:RGD.
DR GO; GO:0051747; F:cytosine C-5 DNA demethylase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0035515; F:oxidative RNA demethylase activity; ISO:RGD.
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:RGD.
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 2: Evidence at transcript level;
KW Cytoplasm; Dioxygenase; DNA damage; DNA repair; Hydroxylation; Iron;
KW Metal-binding; Nucleus; Oxidation; Oxidoreductase; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..295
FT /note="Alpha-ketoglutarate-dependent dioxygenase alkB
FT homolog 3"
FT /id="PRO_0000239280"
FT DOMAIN 172..278
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..45
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"
SQ SEQUENCE 295 AA; 34011 MW; C4D1A094CF9A3293 CRC64;
MGDKRQRARV QGAWATPTKS QSAARPATPA RSRPSQTPGP SWRSKEQQQC DRRFVFKEPQ
LVVRAAPEPR VIDREGVYEI SLSPTGVSRV CLYPGFVDLK EADWILERLC QDVPWKQRMG
IREDITYPQP RLTAWYGELP YTYSRVTMEP NPHWLPVLWT LKSRIEENTG HTFNSLLCNF
YRDEKDSVDW HSDDEPSLGS CPVIASLSFG ATRTFEMRKK PPPEENGDYT YVERVKIPLD
HGTLLIMEGA TQADWQHRVP KEYHSRERRV NLTFRTVYPD PRGAPGDTSA ELPLR
