ALKB2_BOVIN
ID ALKB2_BOVIN Reviewed; 278 AA.
AC Q58DM4; Q0VCG6;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=DNA oxidative demethylase ALKBH2;
DE EC=1.14.11.33 {ECO:0000250|UniProtKB:Q6NS38};
DE AltName: Full=Alkylated DNA repair protein alkB homolog 2;
DE AltName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2;
GN Name=ALKBH2; Synonyms=ABH2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Dioxygenase that repairs alkylated nucleic acid bases by
CC direct reversal oxidative dealkylation. Can process both double-
CC stranded (ds) and single-stranded (ss) DNA substrates, with a strong
CC preference for dsDNA (By similarity). Uses molecular oxygen, 2-
CC oxoglutarate and iron as cofactors to oxidize the alkyl groups that are
CC subsequently released as aldehydes, regenerating the undamaged bases.
CC Probes the base pair stability, locates a weakened base pair and flips
CC the damaged base to accommodate the lesion in its active site for
CC efficient catalysis (By similarity). Repairs monoalkylated bases,
CC specifically N1-methyladenine and N3-methylcytosine, as well as higher
CC order alkyl adducts such as bases modified with exocyclic bridged
CC adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-
CC ethenocytosine and 1,N2-ethenoguanine (By similarity). Acts as a
CC gatekeeper of genomic integrity under alkylation stress. Efficiently
CC repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can
CC cause ss- and dsDNA strand breaks that severely impair rDNA
CC transcription (By similarity). In a response mechanism to DNA damage,
CC associates with PCNA at replication forks to repair alkylated adducts
CC prior to replication (By similarity). {ECO:0000250|UniProtKB:Q6NS38}.
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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30300;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + an N(1)-methyl-2'-deoxyadenosine in double-
CC stranded DNA + O2 = a 2'-deoxyadenosine in double-stranded DNA + CO2
CC + formaldehyde + H(+) + succinate; Xref=Rhea:RHEA:70443, Rhea:RHEA-
CC COMP:14236, Rhea:RHEA-COMP:17897, 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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70444;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70448;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + an N(3)-methyl-2'-deoxycytidine in double-
CC stranded DNA + O2 = a 2'-deoxycytidine in double-stranded DNA + CO2 +
CC formaldehyde + H(+) + succinate; Xref=Rhea:RHEA:70439, Rhea:RHEA-
CC COMP:14237, Rhea:RHEA-COMP:17070, 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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70440;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70436;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 1,N(6)-etheno-2'-deoxyadenosine in double-
CC stranded DNA + H2O + O2 = a 2'-deoxyadenosine in double-stranded DNA
CC + CO2 + glyoxal + succinate; Xref=Rhea:RHEA:70463, Rhea:RHEA-
CC COMP:17897, Rhea:RHEA-COMP:17903, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:34779, ChEBI:CHEBI:90615,
CC ChEBI:CHEBI:189583; Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70464;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 1,N(6)-etheno-2'-deoxyadenosine in single-
CC stranded DNA + H2O + O2 = a 2'-deoxyadenosine in single-stranded DNA
CC + CO2 + glyoxal + succinate; Xref=Rhea:RHEA:70459, Rhea:RHEA-
CC COMP:17896, Rhea:RHEA-COMP:17904, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:34779, ChEBI:CHEBI:90615,
CC ChEBI:CHEBI:189583; Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70460;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 3,N(4)-etheno-2'-deoxycytidine in double-
CC stranded DNA + H2O + O2 = a 2'-deoxycytidine in double-stranded DNA +
CC CO2 + glyoxal + succinate; Xref=Rhea:RHEA:70467, Rhea:RHEA-
CC COMP:17070, Rhea:RHEA-COMP:17905, 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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70468;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
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:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70472;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 1,N(2)-etheno-2'-deoxyguanosine in double-
CC stranded DNA + H2O + O2 = a 2'-deoxyguanosine in double-stranded DNA
CC + CO2 + glyoxal + succinate; Xref=Rhea:RHEA:70487, Rhea:RHEA-
CC COMP:17910, Rhea:RHEA-COMP:17912, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:34779, ChEBI:CHEBI:85445,
CC ChEBI:CHEBI:189586; Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70488;
CC Evidence={ECO:0000250|UniProtKB:Q6NS38};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- ACTIVITY REGULATION: Activated by ascorbate and magnesium ions.
CC {ECO:0000250|UniProtKB:Q6NS38}.
CC -!- SUBUNIT: Interacts with PCNA homotrimer; this interaction is enhanced
CC during the S-phase of the cell cycle. Interacts with nucleolar proteins
CC NCL, UBTF and NPM1. Interacts with XRCC5-XRCC6 heterodimer.
CC {ECO:0000250|UniProtKB:Q6NS38}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6NS38}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q6NS38}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6NS38}. Note=Relocates to the replication foci
CC during S-phase. {ECO:0000250|UniProtKB:Q6NS38}.
CC -!- DOMAIN: The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif,
CC APIM), mediates the colocalization of ALKBH2 with PCNA at the
CC replication foci, coordinating the repair of alkylated DNA damage with
CC DNA replication. {ECO:0000250|UniProtKB:Q6NS38}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR EMBL; BT021573; AAX46420.1; -; mRNA.
DR EMBL; BC120178; AAI20179.1; -; mRNA.
DR RefSeq; NP_001019687.1; NM_001024516.1.
DR RefSeq; XP_005217847.1; XM_005217790.3.
DR RefSeq; XP_005217848.1; XM_005217791.3.
DR RefSeq; XP_005217849.1; XM_005217792.3.
DR AlphaFoldDB; Q58DM4; -.
DR SMR; Q58DM4; -.
DR STRING; 9913.ENSBTAP00000026442; -.
DR PaxDb; Q58DM4; -.
DR Ensembl; ENSBTAT00000026442; ENSBTAP00000026442; ENSBTAG00000019846.
DR Ensembl; ENSBTAT00000075412; ENSBTAP00000062950; ENSBTAG00000019846.
DR GeneID; 511380; -.
DR KEGG; bta:511380; -.
DR CTD; 121642; -.
DR VEuPathDB; HostDB:ENSBTAG00000019846; -.
DR VGNC; VGNC:25833; ALKBH2.
DR eggNOG; ENOG502QTDK; Eukaryota.
DR GeneTree; ENSGT00940000159009; -.
DR InParanoid; Q58DM4; -.
DR OMA; TQHHWQH; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000019846; Expressed in oocyte and 104 other tissues.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0051747; F:cytosine C-5 DNA demethylase activity; ISS:UniProtKB.
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:0035516; F:oxidative DNA demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0000182; F:rDNA binding; IEA:Ensembl.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; ISS:UniProtKB.
DR GO; GO:0035511; P:oxidative DNA demethylation; ISS:UniProtKB.
DR Gene3D; 2.60.120.590; -; 1.
DR InterPro; IPR027450; AlkB-like.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR032852; ALKBH2.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR PANTHER; PTHR31573; PTHR31573; 1.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 2: Evidence at transcript level;
KW Dioxygenase; DNA damage; DNA repair; Iron; Magnesium; Metal-binding;
KW Nucleus; Oxidoreductase; Reference proteome.
FT CHAIN 1..278
FT /note="DNA oxidative demethylase ALKBH2"
FT /id="PRO_0000239274"
FT DOMAIN 151..256
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 3..7
FT /note="PCNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 101..103
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 121..123
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 158
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 160
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 170
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 170
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 172
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 235
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 235
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 247
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 251
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
FT BINDING 253
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6NS38"
SQ SEQUENCE 278 AA; 31053 MW; CAA8E5CB6CCC081F CRC64;
MDRFLVKGAV GSLKRRMEQE QTGGGPAGLA EEEGNSKKNP RRAAPGNGVD SAGLTWGRIR
AEGLNCDYTI LFGKAEADEI FQELEKEVEY FTGALARVQV FGKWHSVPRK QATYGDTGLT
YTFSGLTLSP KPWIPVLERV RDRVSLVTGQ TFNFVLINRY KDGQDHIGEH RDDERELALG
SPIASVSFGA CRDFVFRHKD SRGKHPSRRL EVVRLQLAHG SLLMMNHPTN THWYHSLPVR
KKVLAPRVNL TFRKILPTTK RTTLLTASAS VGSFALHS
