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P0CB42

- ALKB1_MOUSE

UniProt

P0CB42 - ALKB1_MOUSE

Protein

Alkylated DNA repair protein alkB homolog 1

Gene

Alkbh1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 42 (01 Oct 2014)
      Sequence version 1 (13 Oct 2009)
      Previous versions | rss
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    Functioni

    Dioxygenase that repairs alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation. Requires molecular oxygen, alpha-ketoglutarate and iron. Has DNA lyase activity and introduces double-stranded breaks at abasic sites. Cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. DNA lyase activity does not require alpha-ketoglutarate and iron By similarity. May have a role in placental trophoblast lineage differentiation.By similarity1 Publication

    Catalytic activityi

    The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
    DNA-base-CH3 + 2-oxoglutarate + O2 = DNA-base + formaldehyde + succinate + CO2.

    Cofactori

    Binds 1 Fe2+ ion per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei170 – 1701SubstrateBy similarity
    Metal bindingi231 – 2311Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi233 – 2331Iron; catalyticPROSITE-ProRule annotation
    Binding sitei261 – 2611SubstrateBy similarity
    Metal bindingi287 – 2871Iron; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. chemoattractant activity Source: MGI
    2. DNA-(apurinic or apyrimidinic site) lyase activity Source: UniProtKB
    3. ferrous iron binding Source: UniProtKB
    4. methylcytosine dioxygenase activity Source: UniProtKB
    5. protein binding Source: MGI

    GO - Biological processi

    1. cell differentiation Source: MGI
    2. developmental growth Source: MGI
    3. DNA catabolic process, endonucleolytic Source: GOC
    4. DNA dealkylation involved in DNA repair Source: UniProtKB
    5. DNA demethylation Source: UniProtKB
    6. DNA repair Source: UniProtKB
    7. in utero embryonic development Source: MGI
    8. negative regulation of neuron apoptotic process Source: MGI
    9. neuron migration Source: MGI
    10. neuron projection development Source: MGI
    11. oxidative demethylation Source: UniProtKB
    12. placenta development Source: MGI
    13. positive chemotaxis Source: GOC
    14. regulation of gene expression Source: MGI
    15. RNA repair Source: UniProtKB

    Keywords - Molecular functioni

    Dioxygenase, Lyase, Oxidoreductase

    Keywords - Biological processi

    DNA damage, DNA repair, RNA repair

    Keywords - Ligandi

    Iron, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alkylated DNA repair protein alkB homolog 1 (EC:1.14.11.33)
    Alternative name(s):
    Alpha-ketoglutarate-dependent dioxygenase ABH1
    DNA lyase ABH1 (EC:4.2.99.18)
    DNA oxidative demethylase ALKBH1
    Gene namesi
    Name:Alkbh1
    Synonyms:Abh, Alkbh
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:2384034. Alkbh1.

    Subcellular locationi

    Nucleus 1 Publication. Mitochondrion By similarity
    Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli.

    GO - Cellular componenti

    1. mitochondrion Source: UniProtKB
    2. nuclear euchromatin Source: MGI

    Keywords - Cellular componenti

    Mitochondrion, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Intrauterine growth retardation and placental defects. Fertile. Altered expression of trophoblast lineage-specific genes.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 389389Alkylated DNA repair protein alkB homolog 1PRO_0000386453Add
    BLAST

    Proteomic databases

    PRIDEiP0CB42.

    Expressioni

    Developmental stagei

    At E8.5 is highly expressed in the chorion and the ectoplacental cone. At E10.5 is highly expressed in multiple trophoblast lineages (spongiotrophoblasts, giant cell trophoblasts, glycogen cells, and labyrinthine trophoblasts). The highest placental level is at E9.5 and subsequently decreases until parturition.1 Publication

    Gene expression databases

    ArrayExpressiP0CB42.
    BgeeiP0CB42.

    Interactioni

    Subunit structurei

    Monomer By similarity. Interacts with DNAJB6.By similarity1 Publication

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000105782.

    Structurei

    3D structure databases

    ProteinModelPortaliP0CB42.
    SMRiP0CB42. Positions 189-289.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini213 – 347135Fe2OG dioxygenasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 127127Interaction with DNAJB6Add
    BLAST
    Regioni177 – 1793Substrate bindingBy similarity
    Regioni220 – 2223Alpha-ketoglutarate bindingBy similarity
    Regioni338 – 3447Alpha-ketoglutarate bindingBy similarity

    Sequence similaritiesi

    Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG3145.
    GeneTreeiENSGT00390000004599.
    HOGENOMiHOG000033905.
    KOiK10765.
    OMAiKKYSADH.
    OrthoDBiEOG71P2CK.
    PhylomeDBiP0CB42.
    TreeFamiTF314609.

    Family and domain databases

    Gene3Di2.60.120.590. 2 hits.
    InterProiIPR004574. Alkb.
    IPR027450. AlkB-like.
    IPR005123. Oxoglu/Fe-dep_dioxygenase.
    [Graphical view]
    PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00568. alkb. 1 hit.
    PROSITEiPS51471. FE2OG_OXY. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P0CB42-1 [UniParc]FASTAAdd to Basket

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    MGKMAAAVAS LATLAAEPRE DAFRKLFRFY RQSRPGTADL GAVIDFSEAH    50
    LARSPKPGVP QVVRFPLNVS SVTERDAERV GLEPVSKWRA YGLEGYPGFI 100
    FIPNPFLPGC QRHWVKQCLK LYSQKPNVCN LDKHMTKEET QGLWEQSKEV 150
    LRSKEVTKRR PRSLLERLRW VTLGYHYNWD SKKYSADHYT PFPSDLAFLS 200
    EQVATACGFQ GFQAEAGILN YYRLDSTLGI HVDRSELDHS KPLLSFSFGQ 250
    SAIFLLGGLK RDEAPTAMFM HSGDIMVMSG FSRLLNHAVP RVLPHPDGEC 300
    LPHCLETPLP AVLPSNSLVE PCSVEDWQVC ATYLRTARVN MTVRQVLATG 350
    QDFPLEPVEE TKRDIAADGL CHLHDPNSPV KRKRLNPNS 389
    Length:389
    Mass (Da):43,746
    Last modified:October 13, 2009 - v1
    Checksum:iD18C019F0CB9C0A5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CT030249 Genomic DNA. No translation available.
    CCDSiCCDS49120.1.
    RefSeqiNP_001096035.1. NM_001102565.1.
    UniGeneiMm.486235.

    Genome annotation databases

    EnsembliENSMUST00000162961; ENSMUSP00000124565; ENSMUSG00000079036.
    GeneIDi211064.
    KEGGimmu:211064.
    UCSCiuc007oix.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CT030249 Genomic DNA. No translation available.
    CCDSi CCDS49120.1.
    RefSeqi NP_001096035.1. NM_001102565.1.
    UniGenei Mm.486235.

    3D structure databases

    ProteinModelPortali P0CB42.
    SMRi P0CB42. Positions 189-289.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000105782.

    Proteomic databases

    PRIDEi P0CB42.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000162961 ; ENSMUSP00000124565 ; ENSMUSG00000079036 .
    GeneIDi 211064.
    KEGGi mmu:211064.
    UCSCi uc007oix.1. mouse.

    Organism-specific databases

    CTDi 8846.
    MGIi MGI:2384034. Alkbh1.

    Phylogenomic databases

    eggNOGi COG3145.
    GeneTreei ENSGT00390000004599.
    HOGENOMi HOG000033905.
    KOi K10765.
    OMAi KKYSADH.
    OrthoDBi EOG71P2CK.
    PhylomeDBi P0CB42.
    TreeFami TF314609.

    Miscellaneous databases

    ChiTaRSi ALKBH1. mouse.
    NextBioi 373138.
    PROi P0CB42.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P0CB42.
    Bgeei P0CB42.

    Family and domain databases

    Gene3Di 2.60.120.590. 2 hits.
    InterProi IPR004574. Alkb.
    IPR027450. AlkB-like.
    IPR005123. Oxoglu/Fe-dep_dioxygenase.
    [Graphical view ]
    Pfami PF13532. 2OG-FeII_Oxy_2. 1 hit.
    [Graphical view ]
    TIGRFAMsi TIGR00568. alkb. 1 hit.
    PROSITEi PS51471. FE2OG_OXY. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    2. "Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice."
      Pan Z., Sikandar S., Witherspoon M., Dizon D., Nguyen T., Benirschke K., Wiley C., Vrana P., Lipkin S.M.
      Dev. Dyn. 237:316-327(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH DNAJB6, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiALKB1_MOUSE
    AccessioniPrimary (citable) accession number: P0CB42
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 13, 2009
    Last sequence update: October 13, 2009
    Last modified: October 1, 2014
    This is version 42 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    Localizes to the nucleus when expressed as fusion protein with an N-terminal tag (PubMed:18163532). Experiments with the human protein show that the endogenous, unmodified protein localizes to mitochondria (PubMed:18603530), but that a fusion protein with an N-terminal tag is localized in cytoplasm and nucleus (PubMed:18603530).1 Publication

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3