P0CB42 (ALKB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Alkbh1
Synonyms:	Abh, Alkbh

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	389 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	DNA damage DNA repair RNA repair
Cellular component	Mitochondrion Nucleus
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Lyase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	DNA dealkylation involved in DNA repair Inferred from sequence or structural similarity. Source: UniProtKB DNA demethylation Inferred from sequence or structural similarity. Source: UniProtKB RNA repair Inferred from sequence or structural similarity. Source: UniProtKB 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
Cellular_component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB nuclear euchromatin Inferred from direct assay Ref.2. Source: MGI
Molecular_function	DNA-(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 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 389	389	Alkylated DNA repair protein alkB homolog 1		PRO_0000386453
Regions
	Domain	213 – 347	135	Fe2OG dioxygenase
	Region	1 – 127	127	Interaction with DNAJB6
	Region	177 – 179	3	Substrate binding By similarity
	Region	220 – 222	3	Alpha-ketoglutarate binding By similarity
	Region	338 – 344	7	Alpha-ketoglutarate binding By similarity
Sites
	Metal binding	231	1	Iron; catalytic By similarity
	Metal binding	233	1	Iron; catalytic By similarity
	Metal binding	287	1	Iron; catalytic By similarity
	Binding site	170	1	Substrate By similarity
	Binding site	261	1	Substrate By similarity

Sequences

	Sequence		Length	Mass (Da)
	P0CB42 [UniParc]. Last modified October 13, 2009. Version 1. Checksum: D18C019F0CB9C0A5	FASTA	389	43,746
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00858117.
RefSeq	NP_001096035.1. NM_001102565.1.
UniGene	Mm.486235.
3D structure databases
ProteinModelPortal	P0CB42.
SMR	P0CB42. Positions 189-289.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000105782.
Proteomic databases
PRIDE	P0CB42.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000162961; ENSMUSP00000124565; ENSMUSG00000079036.
GeneID	211064.
KEGG	mmu:211064.
UCSC	uc007oix.1. mouse.
Organism-specific databases
CTD	8846.
MGI	MGI:2384034. Alkbh1.
Phylogenomic databases
eggNOG	COG3145.
GeneTree	ENSGT00390000004599.
HOGENOM	HOG000033905.
KO	K10765.
OMA	KKYSADH.
OrthoDB	EOG4868CJ.
Gene expression databases
ArrayExpress	P0CB42.
Bgee	P0CB42.
Family and domain databases
InterPro	IPR004574. Alkb. IPR005123. Oxoglu/Fe-dep_dioxygenase. [Graphical view]
Pfam	PF13532. 2OG-FeII_Oxy_2. 1 hit. [Graphical view]
TIGRFAMs	TIGR00568. alkb. 1 hit.
PROSITE	PS51471. FE2OG_OXY. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ALKBH1. mouse.
NextBio	373138.
SOURCE	Search...

Entry information

Entry name

ALKB1_MOUSE

Accession

Primary (citable) accession number: P0CB42

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 13, 2009
Last sequence update:	October 13, 2009
Last modified:	May 1, 2013
This is version 30 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program