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P0CB42 (ALKB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 41. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Alkbh1
Synonyms:Abh, Alkbh
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length389 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Catalytic activity

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.

Cofactor

Binds 1 Fe2+ ion per subunit.

Subunit structure

Monomer By similarity. Interacts with DNAJB6. Ref.2

Subcellular location

Nucleus. Mitochondrion By similarity. Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli. Ref.2

Developmental stage

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. Ref.2

Disruption phenotype

Intrauterine growth retardation and placental defects. Fertile. Altered expression of trophoblast lineage-specific genes. Ref.2

Sequence similarities

Contains 1 Fe2OG dioxygenase domain.

Caution

Localizes to the nucleus when expressed as fusion protein with an N-terminal tag (Ref.2). 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).

Ontologies

Keywords
   Biological processDNA damage
DNA repair
RNA repair
   Cellular componentMitochondrion
Nucleus
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Lyase
Oxidoreductase
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, endonucleolytic

Inferred from sequence or structural similarity. Source: GOC

DNA dealkylation involved in DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

DNA demethylation

Inferred from sequence or structural similarity. Source: UniProtKB

DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

RNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

cell differentiation

Inferred from mutant phenotype Ref.2. Source: MGI

developmental growth

Inferred from mutant phenotype Ref.2. Source: MGI

in utero embryonic development

Inferred from mutant phenotype Ref.2. Source: MGI

negative regulation of neuron apoptotic process

Inferred from direct assay PubMed 16860792. Source: MGI

neuron migration

Inferred from direct assay PubMed 16860792. Source: MGI

neuron projection development

Inferred from direct assay PubMed 16860792. Source: MGI

oxidative demethylation

Inferred from sequence or structural similarity. Source: UniProtKB

placenta development

Inferred from mutant phenotype Ref.2. Source: MGI

positive chemotaxis

Inferred from direct assay PubMed 16860792. Source: GOC

regulation of gene expression

Inferred from mutant phenotype Ref.2. Source: MGI

   Cellular_componentmitochondrion

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear euchromatin

Inferred from direct assay Ref.2. Source: MGI

   Molecular_functionDNA-(apurinic or apyrimidinic site) lyase activity

Inferred from sequence or structural similarity. Source: UniProtKB

chemoattractant activity

Inferred from direct assay PubMed 16860792. Source: MGI

ferrous iron binding

Inferred from sequence or structural similarity. Source: UniProtKB

methylcytosine dioxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.2. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 389389Alkylated DNA repair protein alkB homolog 1
PRO_0000386453

Regions

Domain213 – 347135Fe2OG dioxygenase
Region1 – 127127Interaction with DNAJB6
Region177 – 1793Substrate binding By similarity
Region220 – 2223Alpha-ketoglutarate binding By similarity
Region338 – 3447Alpha-ketoglutarate binding By similarity

Sites

Metal binding2311Iron; catalytic By similarity
Metal binding2331Iron; catalytic By similarity
Metal binding2871Iron; catalytic By similarity
Binding site1701Substrate By similarity
Binding site2611Substrate By similarity

Sequences

Sequence LengthMass (Da)Tools
P0CB42 [UniParc].

Last modified October 13, 2009. Version 1.
Checksum: D18C019F0CB9C0A5

FASTA38943,746
        10         20         30         40         50         60 
MGKMAAAVAS LATLAAEPRE DAFRKLFRFY RQSRPGTADL GAVIDFSEAH LARSPKPGVP 

        70         80         90        100        110        120 
QVVRFPLNVS SVTERDAERV GLEPVSKWRA YGLEGYPGFI FIPNPFLPGC QRHWVKQCLK 

       130        140        150        160        170        180 
LYSQKPNVCN LDKHMTKEET QGLWEQSKEV LRSKEVTKRR PRSLLERLRW VTLGYHYNWD 

       190        200        210        220        230        240 
SKKYSADHYT PFPSDLAFLS EQVATACGFQ GFQAEAGILN YYRLDSTLGI HVDRSELDHS 

       250        260        270        280        290        300 
KPLLSFSFGQ SAIFLLGGLK RDEAPTAMFM HSGDIMVMSG FSRLLNHAVP RVLPHPDGEC 

       310        320        330        340        350        360 
LPHCLETPLP AVLPSNSLVE PCSVEDWQVC ATYLRTARVN MTVRQVLATG QDFPLEPVEE 

       370        380 
TKRDIAADGL CHLHDPNSPV KRKRLNPNS 

« Hide

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CT030249 Genomic DNA. No translation available.
CCDSCCDS49120.1.
RefSeqNP_001096035.1. NM_001102565.1.
UniGeneMm.486235.

3D structure databases

ProteinModelPortalP0CB42.
SMRP0CB42. Positions 189-289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000105782.

Proteomic databases

PRIDEP0CB42.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000162961; ENSMUSP00000124565; ENSMUSG00000079036.
GeneID211064.
KEGGmmu:211064.
UCSCuc007oix.1. mouse.

Organism-specific databases

CTD8846.
MGIMGI:2384034. Alkbh1.

Phylogenomic databases

eggNOGCOG3145.
GeneTreeENSGT00390000004599.
HOGENOMHOG000033905.
KOK10765.
OMAKKYSADH.
OrthoDBEOG71P2CK.
PhylomeDBP0CB42.
TreeFamTF314609.

Gene expression databases

ArrayExpressP0CB42.
BgeeP0CB42.

Family and domain databases

Gene3D2.60.120.590. 2 hits.
InterProIPR004574. Alkb.
IPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
TIGRFAMsTIGR00568. alkb. 1 hit.
PROSITEPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALKBH1. mouse.
NextBio373138.
PROP0CB42.
SOURCESearch...

Entry information

Entry nameALKB1_MOUSE
AccessionPrimary (citable) accession number: P0CB42
Entry history
Integrated into UniProtKB/Swiss-Prot: October 13, 2009
Last sequence update: October 13, 2009
Last modified: July 9, 2014
This is version 41 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot