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Q96Q83

- ALKB3_HUMAN

UniProt

Q96Q83 - ALKB3_HUMAN

Protein

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3

Gene

ALKBH3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Dioxygenase that repairs alkylated DNA containing 1-methyladenine (1meA) and 3-methylcytosine (3meC) by oxidative demethylation. Has a strong preference for single-stranded DNA. Able to process alkylated 3mC within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKHB3. May also act on RNA. Requires molecular oxygen, alpha-ketoglutarate and iron.4 Publications

    Cofactori

    Binds 1 Fe2+ ion per subunit.

    Enzyme regulationi

    Activated by ascorbate.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei115 – 1151SubstrateBy similarity
    Sitei177 – 1771Susceptible to oxidation
    Metal bindingi191 – 1911Iron; catalytic1 PublicationPROSITE-ProRule annotation
    Metal bindingi193 – 1931Iron; catalytic1 PublicationPROSITE-ProRule annotation
    Binding sitei194 – 1941SubstrateBy similarity
    Metal bindingi257 – 2571Iron; catalytic1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. cytosine C-5 DNA demethylase activity Source: Ensembl
    2. DNA-N1-methyladenine dioxygenase activity Source: UniProtKB
    3. ferrous iron binding Source: UniProtKB
    4. L-ascorbic acid binding Source: UniProtKB-KW
    5. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell proliferation Source: UniProtKB
    2. DNA dealkylation involved in DNA repair Source: UniProtKB
    3. DNA repair Source: UniProtKB
    4. oxidative single-stranded DNA demethylation Source: UniProtKB

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    DNA damage, DNA repair

    Keywords - Ligandi

    Iron, Metal-binding, Vitamin C

    Enzyme and pathway databases

    ReactomeiREACT_1662. ABH3 mediated Reversal of Alkylation Damage.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (EC:1.14.11.-)
    Alternative name(s):
    Alkylated DNA repair protein alkB homolog 3
    DEPC-1
    Prostate cancer antigen 1
    Gene namesi
    Name:ALKBH3
    Synonyms:ABH3, DEPC1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:30141. ALKBH3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi122 – 1221R → A: Decreases activity towards ssDNA by 25%. Loss of activity towards dsDNA.
    Mutagenesisi123 – 1231E → A: Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
    Mutagenesisi131 – 1311R → A: Loss of activity.
    Mutagenesisi177 – 1771L → A or N: Loss of activity against 1-methyladenine.
    Mutagenesisi177 – 1771L → E or Q: Loss of activity.
    Mutagenesisi177 – 1771L → I: Decreases activity against 1-methyladenine.
    Mutagenesisi177 – 1771L → M: No effect.
    Mutagenesisi179 – 1791N → A: Decreases activity by about 60%.
    Mutagenesisi181 – 1811Y → A: Strong decrease of activity.
    Mutagenesisi189 – 1891D → A: Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
    Mutagenesisi191 – 1911H → A: Loss of activity.
    Mutagenesisi193 – 1931D → A: Loss of activity. 1 Publication
    Mutagenesisi257 – 2571H → A: Decreases activity by about 65%. 2 Publications
    Mutagenesisi269 – 2691R → A: Strong decrease of activity.
    Mutagenesisi271 – 2711N → A: No effect.
    Mutagenesisi275 – 2751R → A: Loss of activity.

    Organism-specific databases

    PharmGKBiPA143485293.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 286286Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3PRO_0000239278Add
    BLAST

    Proteomic databases

    MaxQBiQ96Q83.
    PaxDbiQ96Q83.
    PRIDEiQ96Q83.

    PTM databases

    PhosphoSiteiQ96Q83.

    Expressioni

    Tissue specificityi

    Ubiquitous. Detected in heart, pancreas, skeletal muscle, thymus, testis, ovary, spleen, prostate, small intestine, peripheral blood leukocytes, urinary bladder and colon.3 Publications

    Gene expression databases

    ArrayExpressiQ96Q83.
    BgeeiQ96Q83.
    CleanExiHS_ALKBH3.
    GenevestigatoriQ96Q83.

    Organism-specific databases

    HPAiCAB005007.
    HPA009674.

    Interactioni

    Subunit structurei

    Interacts with the TRIP4 complex, notably composed of ASCC3.2 Publications

    Protein-protein interaction databases

    BioGridi128686. 2 interactions.
    IntActiQ96Q83. 3 interactions.
    STRINGi9606.ENSP00000302232.

    Structurei

    Secondary structure

    1
    286
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi74 – 818
    Beta strandi84 – 863
    Beta strandi88 – 936
    Helixi99 – 11214
    Beta strandi119 – 1246
    Beta strandi126 – 1283
    Beta strandi130 – 1378
    Helixi145 – 1484
    Beta strandi151 – 1533
    Helixi156 – 16914
    Beta strandi175 – 1817
    Beta strandi188 – 1914
    Helixi196 – 1983
    Beta strandi204 – 2118
    Beta strandi213 – 2197
    Beta strandi234 – 2396
    Beta strandi244 – 2496
    Helixi251 – 2544
    Beta strandi255 – 2595
    Beta strandi269 – 2757

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2IUWX-ray1.50A70-286[»]
    ProteinModelPortaliQ96Q83.
    SMRiQ96Q83. Positions 70-279.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96Q83.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini172 – 278107Fe2OG dioxygenasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni141 – 1433Substrate bindingBy similarity
    Regioni179 – 1813Alpha-ketoglutarate binding
    Regioni269 – 2757Alpha-ketoglutarate binding

    Sequence similaritiesi

    Belongs to the alkB family.Curated
    Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG3145.
    HOGENOMiHOG000207105.
    HOVERGENiHBG056732.
    InParanoidiQ96Q83.
    KOiK10860.
    OMAiDRGPRIN.
    PhylomeDBiQ96Q83.
    TreeFamiTF331732.

    Family and domain databases

    Gene3Di2.60.120.590. 1 hit.
    InterProiIPR027450. AlkB-like.
    IPR005123. Oxoglu/Fe-dep_dioxygenase.
    [Graphical view]
    PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
    [Graphical view]
    PROSITEiPS51471. FE2OG_OXY. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96Q83-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MEEKRRRARV QGAWAAPVKS QAIAQPATTA KSHLHQKPGQ TWKNKEHHLS    50
    DREFVFKEPQ QVVRRAPEPR VIDREGVYEI SLSPTGVSRV CLYPGFVDVK 100
    EADWILEQLC QDVPWKQRTG IREDITYQQP RLTAWYGELP YTYSRITMEP 150
    NPHWHPVLRT LKNRIEENTG HTFNSLLCNL YRNEKDSVDW HSDDEPSLGR 200
    CPIIASLSFG ATRTFEMRKK PPPEENGDYT YVERVKIPLD HGTLLIMEGA 250
    TQADWQHRVP KEYHSREPRV NLTFRTVYPD PRGAPW 286
    Length:286
    Mass (Da):33,375
    Last modified:December 1, 2001 - v1
    Checksum:iF6563635B1F217D7
    GO
    Isoform 2 (identifier: Q96Q83-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         73-74: DR → E
         125-172: ITYQQPRLTA...NRIEENTGHT → SILQLTFKKS...ILTRTRLWAP
         173-286: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:170
    Mass (Da):19,310
    Checksum:i9BC42BA5B40B035C
    GO

    Sequence cautioni

    The sequence AAH15155.1 differs from that shown. Reason: Erroneous initiation.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti164 – 1641R → C.1 Publication
    Corresponds to variant rs2271815 [ dbSNP | Ensembl ].
    VAR_026632
    Natural varianti228 – 2281D → E.2 Publications
    Corresponds to variant rs2434470 [ dbSNP | Ensembl ].
    VAR_026631

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei73 – 742DR → E in isoform 2. 1 PublicationVSP_019125
    Alternative sequencei125 – 17248ITYQQ…NTGHT → SILQLTFKKSAPVSGTATAP QSCWYERPSPPHIPGPAILT RTRLWAP in isoform 2. 1 PublicationVSP_019126Add
    BLAST
    Alternative sequencei173 – 286114Missing in isoform 2. 1 PublicationVSP_019127Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB042029 mRNA. Translation: BAB70508.1.
    DQ196343 Genomic DNA. Translation: ABA27096.1.
    AC087521 Genomic DNA. No translation available.
    CH471064 Genomic DNA. Translation: EAW68078.1.
    BC015155 mRNA. Translation: AAH15155.1. Different initiation.
    BC103812 mRNA. Translation: AAI03813.1.
    BC103813 mRNA. Translation: AAI03814.1.
    BC103814 mRNA. Translation: AAI03815.1.
    BC067257 mRNA. Translation: AAH67257.1.
    CCDSiCCDS7906.1. [Q96Q83-1]
    RefSeqiNP_631917.1. NM_139178.3. [Q96Q83-1]
    UniGeneiHs.720708.

    Genome annotation databases

    EnsembliENST00000302708; ENSP00000302232; ENSG00000166199. [Q96Q83-1]
    ENST00000530803; ENSP00000436788; ENSG00000166199. [Q96Q83-2]
    GeneIDi221120.
    KEGGihsa:221120.
    UCSCiuc001mxs.2. human. [Q96Q83-1]

    Polymorphism databases

    DMDMi74752087.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB042029 mRNA. Translation: BAB70508.1 .
    DQ196343 Genomic DNA. Translation: ABA27096.1 .
    AC087521 Genomic DNA. No translation available.
    CH471064 Genomic DNA. Translation: EAW68078.1 .
    BC015155 mRNA. Translation: AAH15155.1 . Different initiation.
    BC103812 mRNA. Translation: AAI03813.1 .
    BC103813 mRNA. Translation: AAI03814.1 .
    BC103814 mRNA. Translation: AAI03815.1 .
    BC067257 mRNA. Translation: AAH67257.1 .
    CCDSi CCDS7906.1. [Q96Q83-1 ]
    RefSeqi NP_631917.1. NM_139178.3. [Q96Q83-1 ]
    UniGenei Hs.720708.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2IUW X-ray 1.50 A 70-286 [» ]
    ProteinModelPortali Q96Q83.
    SMRi Q96Q83. Positions 70-279.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 128686. 2 interactions.
    IntActi Q96Q83. 3 interactions.
    STRINGi 9606.ENSP00000302232.

    Chemistry

    DrugBanki DB00126. Vitamin C.

    PTM databases

    PhosphoSitei Q96Q83.

    Polymorphism databases

    DMDMi 74752087.

    Proteomic databases

    MaxQBi Q96Q83.
    PaxDbi Q96Q83.
    PRIDEi Q96Q83.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302708 ; ENSP00000302232 ; ENSG00000166199 . [Q96Q83-1 ]
    ENST00000530803 ; ENSP00000436788 ; ENSG00000166199 . [Q96Q83-2 ]
    GeneIDi 221120.
    KEGGi hsa:221120.
    UCSCi uc001mxs.2. human. [Q96Q83-1 ]

    Organism-specific databases

    CTDi 221120.
    GeneCardsi GC11P043859.
    HGNCi HGNC:30141. ALKBH3.
    HPAi CAB005007.
    HPA009674.
    MIMi 610603. gene.
    neXtProti NX_Q96Q83.
    PharmGKBi PA143485293.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3145.
    HOGENOMi HOG000207105.
    HOVERGENi HBG056732.
    InParanoidi Q96Q83.
    KOi K10860.
    OMAi DRGPRIN.
    PhylomeDBi Q96Q83.
    TreeFami TF331732.

    Enzyme and pathway databases

    Reactomei REACT_1662. ABH3 mediated Reversal of Alkylation Damage.

    Miscellaneous databases

    EvolutionaryTracei Q96Q83.
    GenomeRNAii 221120.
    NextBioi 91204.
    PROi Q96Q83.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96Q83.
    Bgeei Q96Q83.
    CleanExi HS_ALKBH3.
    Genevestigatori Q96Q83.

    Family and domain databases

    Gene3Di 2.60.120.590. 1 hit.
    InterProi IPR027450. AlkB-like.
    IPR005123. Oxoglu/Fe-dep_dioxygenase.
    [Graphical view ]
    Pfami PF13532. 2OG-FeII_Oxy_2. 1 hit.
    [Graphical view ]
    PROSITEi PS51471. FE2OG_OXY. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Homo sapiens mRNA expressed in prostate cancer and thymus."
      Tsujikawa K., Konishi N., Ono Y., Ichijou T., Sakamoto K., Yamamoto H.
      Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Fetal thymus and Prostatic carcinoma.
    2. NIEHS SNPs program
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-164 AND GLU-228.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT GLU-228.
      Tissue: Lung and PNS.
    6. Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    7. "Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA."
      Aas P.A., Otterlei M., Falnes P.O., Vaagboe C.B., Skorpen F., Akbari M., Sundheim O., Bjoeraas M., Slupphaug G., Seeberg E., Krokan H.E.
      Nature 421:859-863(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    8. "Repair of methylation damage in DNA and RNA by mammalian AlkB homologues."
      Lee D.-H., Jin S.-G., Cai S., Chen Y., Pfeifer G.P., O'Connor T.R.
      J. Biol. Chem. 280:39448-39459(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-193 AND HIS-257, TISSUE SPECIFICITY.
    9. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    10. "DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation."
      Dango S., Mosammaparast N., Sowa M.E., Xiong L.J., Wu F., Park K., Rubin M., Gygi S., Harper J.W., Shi Y.
      Mol. Cell 44:373-384(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ALKBH3, MUTAGENESIS OF HIS-257.
    11. "Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage."
      Sundheim O., Vaagboe C.B., Bjoeraas M., Sousa M.M.L., Talstad V., Aas P.A., Drabloes F., Krokan H.E., Tainer J.A., Slupphaug G.
      EMBO J. 25:3389-3397(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 70-286 IN COMPLEX WITH ALPHA-KETOGLUTARATE AND IRON, IDENTIFICATION BY MASS SPECTROMETRY, OXIDATION AT LEU-177.

    Entry informationi

    Entry nameiALKB3_HUMAN
    AccessioniPrimary (citable) accession number: Q96Q83
    Secondary accession number(s): A6NDJ1
    , Q3SYI0, Q6NX57, Q96BU8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2006
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 115 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3