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P0CB42

- ALKB1_MOUSE

UniProt

P0CB42 - ALKB1_MOUSE

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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

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 Fe(2+) 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

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
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. nuclear euchromatin Source: MGI
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.
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

« 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.
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

MaxQBi P0CB42.
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.
InParanoidi P0CB42.
KOi K10765.
OMAi KKYSADH.
OrthoDBi EOG71P2CK.
PhylomeDBi P0CB42.
TreeFami TF314609.

Miscellaneous databases

ChiTaRSi Alkbh1. mouse.
NextBioi 373138.
PROi P0CB42.
SOURCEi Search...

Gene expression databases

Bgeei P0CB42.
ExpressionAtlasi P0CB42. baseline and differential.

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

« 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: November 26, 2014
This is version 44 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