UniProtKB - Q6P6J4 (ALKB2_MOUSE)
DNA oxidative demethylase ALKBH2
Alkbh2
Functioni
Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA (PubMed:16174769, PubMed:16642038, PubMed:18519673).
Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis (PubMed:16174769, PubMed:16642038, PubMed:18519673) (By similarity).
Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine (By similarity).
Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription (By similarity).
In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (By similarity).
By similarity3 PublicationsCatalytic activityi
- 2-oxoglutarate + a methylated nucleobase within DNA + O2 = a nucleobase within DNA + CO2 + formaldehyde + succinate3 PublicationsEC:1.14.11.333 PublicationsThis reaction proceeds in the forward3 Publications direction.
- 2-oxoglutarate + an N1-methyl-2ʼ-deoxyadenosine in double-stranded DNA + O2 = a 2ʼ-deoxyadenosine in double-stranded DNA + CO2 + formaldehyde + H+ + succinate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 2-oxoglutarate + an N1-methyl-2ʼ-deoxyadenosine in single-stranded DNA + O2 = a 2ʼ-deoxyadenosine in single-stranded DNA + CO2 + formaldehyde + H+ + succinate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 2-oxoglutarate + an N3-methyl-2ʼ-deoxycytidine in double-stranded DNA + O2 = a 2'-deoxycytidine in double-stranded DNA + CO2 + formaldehyde + H+ + succinate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 2-oxoglutarate + an N3-methyl-2ʼ-deoxycytidine in single-stranded DNA + O2 = a 2'-deoxycytidine in single-stranded DNA + CO2 + formaldehyde + H+ + succinate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 2-oxoglutarate + a 1,N6-etheno-2ʼ-deoxyadenosine in double-stranded DNA + H2O + O2 = a 2ʼ-deoxyadenosine in double-stranded DNA + CO2 + glyoxal + succinate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 2-oxoglutarate + a 1,N6-etheno-2ʼ-deoxyadenosine in single-stranded DNA + H2O + O2 = a 2ʼ-deoxyadenosine in single-stranded DNA + CO2 + glyoxal + succinateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-oxoglutarate + a 3,N4-etheno-2ʼ-deoxycytidine in double-stranded DNA + H2O + O2 = a 2'-deoxycytidine in double-stranded DNA + CO2 + glyoxal + succinateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-oxoglutarate + a 3,N4-etheno-2ʼ-deoxycytidine in single-stranded DNA + H2O + O2 = a 2'-deoxycytidine in single-stranded DNA + CO2 + glyoxal + succinateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-oxoglutarate + a 1,N2-etheno-2ʼ-deoxyguanosine in double-stranded DNA + H2O + O2 = a 2ʼ-deoxyguanosine in double-stranded DNA + CO2 + glyoxal + succinateBy similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 137 | 2-oxoglutarateBy similarity | 1 | |
Binding sitei | 139 | 2-oxoglutarateBy similarity | 1 | |
Metal bindingi | 149 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Binding sitei | 149 | 2-oxoglutarateBy similarity | 1 | |
Metal bindingi | 151 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Binding sitei | 152 | SubstrateBy similarity | 1 | |
Metal bindingi | 214 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Binding sitei | 214 | 2-oxoglutarateBy similarity | 1 | |
Binding sitei | 226 | 2-oxoglutarateBy similarity | 1 | |
Binding sitei | 230 | 2-oxoglutarateBy similarity | 1 | |
Binding sitei | 232 | 2-oxoglutarateBy similarity | 1 |
GO - Molecular functioni
- 2-oxoglutarate-dependent dioxygenase activity Source: MGI
- cytosine C-5 DNA demethylase activity Source: MGI
- DNA-N1-methyladenine dioxygenase activity Source: UniProtKB
- ferrous iron binding Source: UniProtKB
- oxidative DNA demethylase activity Source: UniProtKB-EC
GO - Biological processi
- DNA dealkylation involved in DNA repair Source: UniProtKB
- oxidative DNA demethylation Source: UniProtKB
Keywordsi
Molecular function | Dioxygenase, Oxidoreductase |
Biological process | DNA damage, DNA repair |
Ligand | Iron, Magnesium, Metal-binding |
Names & Taxonomyi
Protein namesi | Recommended name: DNA oxidative demethylase ALKBH2 (EC:1.14.11.333 Publications)Alternative name(s): Alkylated DNA repair protein alkB homolog 2 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2 |
Gene namesi | Name:Alkbh2 Synonyms:Abh2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2141032, Alkbh2 |
VEuPathDBi | HostDB:ENSMUSG00000044339 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
- nucleolus By similarity
- nucleoplasm By similarity
Note: Relocates to the replication foci during S-phase.By similarity
Nucleus
- nucleoplasm Source: MGI
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 151 | D → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 214 | H → A: Reduces activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000239276 | 1 – 239 | DNA oxidative demethylase ALKBH2Add BLAST | 239 |
Proteomic databases
EPDi | Q6P6J4 |
MaxQBi | Q6P6J4 |
PaxDbi | Q6P6J4 |
PeptideAtlasi | Q6P6J4 |
PRIDEi | Q6P6J4 |
ProteomicsDBi | 296096 |
PTM databases
PhosphoSitePlusi | Q6P6J4 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000044339, Expressed in embryo and 169 other tissues |
Genevisiblei | Q6P6J4, MM |
Interactioni
Subunit structurei
Interacts with PCNA homotrimer; this interaction is enhanced during the S-phase of the cell cycle.
Interacts with nucleolar proteins NCL, UBTF and NPM1.
Interacts with XRCC5-XRCC6 heterodimer.
By similarityProtein-protein interaction databases
STRINGi | 10090.ENSMUSP00000056043 |
Miscellaneous databases
RNActi | Q6P6J4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 130 – 235 | Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST | 106 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 11 – 32 | DisorderedSequence analysisAdd BLAST | 22 | |
Regioni | 80 – 82 | Substrate bindingBy similarity | 3 | |
Regioni | 100 – 102 | Substrate bindingBy similarity | 3 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 3 – 7 | PCNA-bindingBy similarity | 5 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QTDK, Eukaryota |
GeneTreei | ENSGT00940000159009 |
HOGENOMi | CLU_048788_5_0_1 |
InParanoidi | Q6P6J4 |
OMAi | TQHHWQH |
OrthoDBi | 1379174at2759 |
PhylomeDBi | Q6P6J4 |
TreeFami | TF331732 |
Family and domain databases
Gene3Di | 2.60.120.590, 1 hit |
InterProi | View protein in InterPro IPR027450, AlkB-like IPR037151, AlkB-like_sf IPR032852, ALKBH2 IPR005123, Oxoglu/Fe-dep_dioxygenase |
PANTHERi | PTHR31573, PTHR31573, 1 hit |
Pfami | View protein in Pfam PF13532, 2OG-FeII_Oxy_2, 1 hit |
PROSITEi | View protein in PROSITE PS51471, FE2OG_OXY, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MDKFLVRPDL RDLQGGGEEP APTGGASGDL KSPDWRHLRA EGLSCDYTVL
60 70 80 90 100
FGKAEADKIF RELEQEVEYF TGALAKVQVF GKWHSVPRKQ ATYGDAGLTY
110 120 130 140 150
TFSGLTLTPK PWVPVLERVR DRVCEVTGQT FNFVLVNRYK DGCDHIGEHR
160 170 180 190 200
DDERELAPGS PIASVSFGAC RDFIFRHKDS RGKRPRRTVE VVRLQLAHGS
210 220 230
LLMMNPPTNT HWYHSLPIRK RVLAPRVNLT FRKILPTKK
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2JER8 | A0A0G2JER8_MOUSE | DNA oxidative demethylase ALKBH2 | Alkbh2 | 44 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 149 | H → Q in BAC37576 (PubMed:16141072).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK079195 mRNA Translation: BAC37576.1 BC062188 mRNA Translation: AAH62188.1 |
CCDSi | CCDS19559.1 |
RefSeqi | NP_778181.2, NM_175016.2 XP_006530352.1, XM_006530289.3 XP_006530353.1, XM_006530290.3 XP_006530354.1, XM_006530291.2 XP_006530355.1, XM_006530292.3 |
Genome annotation databases
Ensembli | ENSMUST00000053657; ENSMUSP00000056043; ENSMUSG00000044339 ENSMUST00000112279; ENSMUSP00000107898; ENSMUSG00000044339 |
GeneIDi | 231642 |
KEGGi | mmu:231642 |
UCSCi | uc008yzd.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK079195 mRNA Translation: BAC37576.1 BC062188 mRNA Translation: AAH62188.1 |
CCDSi | CCDS19559.1 |
RefSeqi | NP_778181.2, NM_175016.2 XP_006530352.1, XM_006530289.3 XP_006530353.1, XM_006530290.3 XP_006530354.1, XM_006530291.2 XP_006530355.1, XM_006530292.3 |
3D structure databases
AlphaFoldDBi | Q6P6J4 |
SMRi | Q6P6J4 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000056043 |
PTM databases
PhosphoSitePlusi | Q6P6J4 |
Proteomic databases
EPDi | Q6P6J4 |
MaxQBi | Q6P6J4 |
PaxDbi | Q6P6J4 |
PeptideAtlasi | Q6P6J4 |
PRIDEi | Q6P6J4 |
ProteomicsDBi | 296096 |
Protocols and materials databases
Antibodypediai | 4403, 146 antibodies from 29 providers |
DNASUi | 231642 |
Genome annotation databases
Ensembli | ENSMUST00000053657; ENSMUSP00000056043; ENSMUSG00000044339 ENSMUST00000112279; ENSMUSP00000107898; ENSMUSG00000044339 |
GeneIDi | 231642 |
KEGGi | mmu:231642 |
UCSCi | uc008yzd.1, mouse |
Organism-specific databases
CTDi | 121642 |
MGIi | MGI:2141032, Alkbh2 |
VEuPathDBi | HostDB:ENSMUSG00000044339 |
Phylogenomic databases
eggNOGi | ENOG502QTDK, Eukaryota |
GeneTreei | ENSGT00940000159009 |
HOGENOMi | CLU_048788_5_0_1 |
InParanoidi | Q6P6J4 |
OMAi | TQHHWQH |
OrthoDBi | 1379174at2759 |
PhylomeDBi | Q6P6J4 |
TreeFami | TF331732 |
Miscellaneous databases
BioGRID-ORCSi | 231642, 2 hits in 110 CRISPR screens |
PROi | PR:Q6P6J4 |
RNActi | Q6P6J4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000044339, Expressed in embryo and 169 other tissues |
Genevisiblei | Q6P6J4, MM |
Family and domain databases
Gene3Di | 2.60.120.590, 1 hit |
InterProi | View protein in InterPro IPR027450, AlkB-like IPR037151, AlkB-like_sf IPR032852, ALKBH2 IPR005123, Oxoglu/Fe-dep_dioxygenase |
PANTHERi | PTHR31573, PTHR31573, 1 hit |
Pfami | View protein in Pfam PF13532, 2OG-FeII_Oxy_2, 1 hit |
PROSITEi | View protein in PROSITE PS51471, FE2OG_OXY, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ALKB2_MOUSE | |
Accessioni | Q6P6J4Primary (citable) accession number: Q6P6J4 Secondary accession number(s): Q8C591 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2006 |
Last sequence update: | July 5, 2004 | |
Last modified: | May 25, 2022 | |
This is version 126 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families