An official website of the United States government

DNA oxidative demethylase ALKBH2 (human)

Protein
Encoding Gene
Dates
  • Create:
    2017-04-15
  • Modify:
    2025-01-17
Description
A DNA oxidative demethylase ALKBH2 that is encoded in the genome of human.
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 (PMID: 12486230, PMID: 12594517, PMID: 16174769, PMID: 20714506, PMID: 23972994, PMID: 25797601). 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 (PMID: 18432238, PMID: 22659876). 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 (PMID: 12486230, PMID: 12594517, PMID: 16174769, PMID: 20714506, PMID: 23972994, PMID: 25797601, PMID: 26408825). 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 (PMID: 23972994). In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (PMID: 19736315, PMID: 26408825).

1 Names and Identifiers

1.1 Synonyms

  • DNA oxidative demethylase ALKBH2
  • EC 1.14.11.33
  • Alkylated DNA repair protein alkB homolog 2
  • Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2
  • Oxy DC1

1.1.1 MeSH Entry Terms

  • Alkylated DNA Repair Protein AlkB Homolog 2
  • Alpha-ketoglutarate-Dependent Dioxygenase AlkB Homolog 2
  • DNA Oxidative Demethylase ALKBH2
  • Oxy DC1 Protein

1.2 Other Identifiers

1.2.1 RefSeq Accession

1.2.2 UniProt ID

1.2.3 Enzyme Commission (EC) Number

1.2.4 PRO ID

1.2.5 ChEMBL Target ID

1.2.6 DrugBank Target ID

1.2.7 NCBI Proteins

1.2.8 GlyCosmos Protein

1.2.9 Pharos Target

1.2.10 Open Targets ID

1.2.11 STRING Protein ID

1.2.12 Wikidata

1.2.13 neXtProt Accession

1.2.14 HPA ID

1.2.15 BRENDA EC Number

1.2.16 IntAct Protein

1.2.17 InterPro Protein

3 Chemicals and Bioactivities

3.1 Tested Compounds

4 BioAssays

5 Sequence

>sp|Q6NS38|ALKB2_HUMAN DNA oxidative demethylase ALKBH2 (Run BLAST)

MDRFLVKGAQGGLLRKQEEQEPTGEEPAVLGGDKESTRKRPRREAPGNGGHSAGPSWRHIRAEGLDCSYTVLFGKAEADEIFQELEKEVEYFTGALARVQVFGKWHSVPRKQATYGDAGLTYTFSGLTLSPKPWIPVLERIRDHVSGVTGQTFNFVLINRYKDGCDHIGEHRDDERELAPGSPIASVSFGACRDFVFRHKDSRGKSPSRRVAVVRLPLAHGSLLMMNHPTNTHWYHSLPVRKKVLAPRVNLTFRKILLTKK

6 3D Structures

6.1 PDB Structures

6.2 NCBI Protein Structures

6.3 AlphaFold Structures

Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605

7 Domains

7.1 CDD Domains

7.2 InterPro Domains

8 Interactions and Pathways

8.1 Chemical-Protein Interactions

8.2 Interactions

8.3 Pathways

9 Biochemical Reactions

10 Target Development Level

11 Literature

11.1 Consolidated References

11.2 NLM Curated PubMed Citations

12 Patents

13 Classification

13.1 MeSH Tree

13.2 ChEMBL Target Tree

13.3 Enzyme Classification

14 Information Sources

  1. NCBI Protein
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  2. PubChem
  3. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase
    https://meshb.nlm.nih.gov/record/ui?ui=D000071499
  4. BioGRID
    LICENSE
    The MIT License (MIT); Copyright Mike Tyers Lab
    https://wiki.thebiogrid.org/doku.php/terms_and_conditions
  5. STRING: functional protein association networks
  6. BRENDA: Enzyme Functional Data
    LICENSE
    The usage of the BRENDA data is licensed under Creative Commons Attribution License CC BY 4.0.
    https://www.brenda-enzymes.org/license.php
  7. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  8. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  9. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  10. GlyCosmos Glycoscience Portal
    LICENSE
    All copyrightable parts of the datasets in GlyCosmos are under the Creative Commons Attribution (CC BY 4.0) License.
    https://glycosmos.org/license
  11. Human Protein Atlas (HPA)
    LICENSE
    The Human Protein Atlas is licensed under the Creative Commons Attribution-ShareAlike 3.0 International License for all copyrightable parts of our database.
    https://www.proteinatlas.org/about/licence
  12. IntAct Molecular Interaction Database
    LICENSE
    Creative Commons Attribution 4.0 International (CC BY 4.0) License
    https://www.ebi.ac.uk/intact/about#license_privacy
  13. InterPro
    LICENSE
    All of the InterPro, Pfam, PRINTS and SFLD downloadable data provided on the InterPro website is freely available under CC0 1.0 Universal (CC0 1.0) Public Domain Dedication.
    https://www.ebi.ac.uk/interpro/about/license/
  14. NCBI Conserved Domains (CDD)
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  15. NCBI Structure
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  16. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
    alkB homolog 2, alpha-ketoglutarate dependent dioxygenase
    https://platform.opentargets.org/target/ENSG00000189046
  17. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
    DNA oxidative demethylase ALKBH2
    https://pharos.nih.gov/targets/Q6NS38
  18. Protein Ontology
    LICENSE
    PRO is distributed under the Creative Commons CC-BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
  19. UniProt
    LICENSE
    We have chosen to apply the Creative Commons Attribution (CC BY 4.0, http://creativecommons.org/licenses/by/4.0/) License to all copyrightable parts of our databases.
    https://www.uniprot.org/help/license
  20. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  21. Swiss Institute of Bioinformatics neXtProt
    LICENSE
    Creative Commons Attribution 4.0 International (CC BY 4.0)
    https://www.nextprot.org/help/faq
  22. Wikidata
    AlkB homolog 2, alpha-ketoglutarate dependent dioxygenase
    https://www.wikidata.org/wiki/Q21111312
  23. Swiss Institute of Bioinformatics ENZYME
    LICENSE
    Copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/).
    https://enzyme.expasy.org/enzyme.get
    Enzyme Classification
    https://enzyme.expasy.org/
  24. AlphaFold DB
    LICENSE
    All of the data provided is freely available for both academic and commercial use under Creative Commons Attribution 4.0 (CC-BY 4.0) licence terms.
    https://alphafold.ebi.ac.uk/faq
  25. Rhea - annotated reactions database
    LICENSE
    Rhea has chosen to apply the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). This means that you are free to copy, distribute, display and make commercial use of the database in all legislations, provided you credit (cite) Rhea.
    https://www.rhea-db.org/help/license-disclaimer
CONTENTS