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Protein

Alkylated DNA repair protein alkB homolog 1

Gene

Alkbh1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Fe2+Note: 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. DNA-(apurinic or apyrimidinic site) lyase activity Source: UniProtKB
  2. ferrous iron binding Source: UniProtKB
  3. methylcytosine dioxygenase activity Source: UniProtKB

GO - Biological processi

  1. DNA catabolic process, endonucleolytic Source: GOC
  2. DNA dealkylation involved in DNA repair Source: UniProtKB
  3. DNA demethylation Source: UniProtKB
  4. DNA repair Source: UniProtKB
  5. oxidative demethylation Source: UniProtKB
  6. RNA repair Source: UniProtKB
Complete GO annotation...

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. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

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

MaxQBiP0CB42.
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

BgeeiP0CB42.
ExpressionAtlasiP0CB42. baseline and differential.

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.
InParanoidiP0CB42.
KOiK10765.
OMAiGFCHLDD.
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

« Hide

        10         20         30         40         50
MGKMAAAVAS LATLAAEPRE DAFRKLFRFY RQSRPGTADL GAVIDFSEAH
60 70 80 90 100
LARSPKPGVP QVVRFPLNVS SVTERDAERV GLEPVSKWRA YGLEGYPGFI
110 120 130 140 150
FIPNPFLPGC QRHWVKQCLK LYSQKPNVCN LDKHMTKEET QGLWEQSKEV
160 170 180 190 200
LRSKEVTKRR PRSLLERLRW VTLGYHYNWD SKKYSADHYT PFPSDLAFLS
210 220 230 240 250
EQVATACGFQ GFQAEAGILN YYRLDSTLGI HVDRSELDHS KPLLSFSFGQ
260 270 280 290 300
SAIFLLGGLK RDEAPTAMFM HSGDIMVMSG FSRLLNHAVP RVLPHPDGEC
310 320 330 340 350
LPHCLETPLP AVLPSNSLVE PCSVEDWQVC ATYLRTARVN MTVRQVLATG
360 370 380
QDFPLEPVEE TKRDIAADGL CHLHDPNSPV KRKRLNPNS
Length:389
Mass (Da):43,746
Last modified:October 13, 2009 - v1
Checksum:iD18C019F0CB9C0A5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
CT030249 Genomic DNA. No translation available.
CCDSiCCDS49120.1.
RefSeqiNP_001096035.1. NM_001102565.1.
UniGeneiMm.486235.

3D structure databases

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000105782.

Proteomic databases

MaxQBiP0CB42.
PRIDEiP0CB42.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8846.
MGIiMGI:2384034. Alkbh1.

Phylogenomic databases

eggNOGiCOG3145.
GeneTreeiENSGT00390000004599.
HOGENOMiHOG000033905.
InParanoidiP0CB42.
KOiK10765.
OMAiGFCHLDD.
OrthoDBiEOG71P2CK.
PhylomeDBiP0CB42.
TreeFamiTF314609.

Miscellaneous databases

ChiTaRSiAlkbh1. mouse.
NextBioi373138.
PROiP0CB42.
SOURCEiSearch...

Gene expression databases

BgeeiP0CB42.
ExpressionAtlasiP0CB42. baseline and differential.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: February 4, 2015
This is version 46 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.