Q6NS38 (ALKB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2
EC=1.14.11.-

Alternative name(s):
Alkylated DNA repair protein alkB homolog 2
Oxy DC1

Gene names

Name:	ALKBH2
Synonyms:	ABH2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Ref.3 Ref.4 Ref.5 Ref.6 Ref.8
Cofactor	Binds 1 Fe2+ ion per subunit. Ref.6 Ref.8
Enzyme regulation	Activated by ascorbate and magnesium ions. Ref.3 Ref.6
Subcellular location	Nucleus. Note: Detected in replication foci during S-phase. Ref.3 Ref.4
Tissue specificity	Detected in colon, small intestine, ovary, testis, prostate, skeletal muscle, heart, liver and urinary bladder. Ref.3 Ref.5
Sequence similarities	Belongs to the alkB family. Contains 1 Fe2OG dioxygenase domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Magnesium Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA dealkylation involved in DNA repair Inferred from direct assay Ref.8. Source: UniProtKB oxidative DNA demethylation Inferred from direct assay Ref.8. Source: UniProtKB
Cellular component	nucleoplasm Traceable author statement. Source: Reactome
Molecular function	DNA-N1-methyladenine dioxygenase activity Inferred from direct assay Ref.8. Source: UniProtKB cytosine C-5 DNA demethylase activity Inferred from direct assay Ref.8. Source: UniProtKB ferrous iron binding Inferred from direct assay Ref.8. 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 – 261

261

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2

PRO_0000239275

Regions

Domain

152 – 257

106

Fe2OG dioxygenase

Region

102 – 104

3

Substrate binding

Region

122 – 124

3

Substrate binding

Region

159 – 161

3

Alpha-ketoglutarate binding

Region

248 – 254

7

Alpha-ketoglutarate binding

Sites

Metal binding

171

1

Iron; catalytic

Metal binding

173

1

Iron; catalytic

Metal binding

236

1

Iron; catalytic

Binding site

174

1

Substrate

Natural variations

Natural variant

203

1

R → H.
Corresponds to variant rs33962311 [ dbSNP | Ensembl ].

VAR_048223

Experimental info

Mutagenesis

173

1

D → A: Loss of activity. Ref.5

Mutagenesis

236

1

H → A: Reduced activity. Ref.5

Sequence conflict

43

1

R → G in AAV28301. Ref.1

Secondary structure

1

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261

Helix Strand Turn

Details...

Beta strand

58 – 62

5

Beta strand

65 – 71

7

Helix

75 – 88

14

Helix

94 – 97

4

Beta strand

98 – 101

4

Beta strand

104 – 107

4

Beta strand

109 – 117

9

Beta strand

122 – 124

3

Beta strand

127 – 129

3

Helix

136 – 149

14

Beta strand

154 – 163

10

Beta strand

168 – 171

4

Beta strand

176 – 178

3

Beta strand

184 – 191

8

Beta strand

193 – 199

7

Helix

200 – 202

3

Beta strand

204 – 206

3

Beta strand

214 – 218

5

Beta strand

222 – 226

5

Helix

230 – 233

4

Beta strand

234 – 238

5

Beta strand

248 – 254

7

Sequences

	Sequence		Length	Mass (Da)
	Q6NS38 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: A376E13F92621A01	FASTA	261	29,322
	10 20 30 40 50 60 MDRFLVKGAQ GGLLRKQEEQ EPTGEEPAVL GGDKESTRKR PRREAPGNGG HSAGPSWRHI 70 80 90 100 110 120 RAEGLDCSYT VLFGKAEADE IFQELEKEVE YFTGALARVQ VFGKWHSVPR KQATYGDAGL 130 140 150 160 170 180 TYTFSGLTLS PKPWIPVLER IRDHVSGVTG QTFNFVLINR YKDGCDHIGE HRDDERELAP 190 200 210 220 230 240 GSPIASVSFG ACRDFVFRHK DSRGKSPSRR VAVVRLPLAH GSLLMMNHPT NTHWYHSLPV 250 260 RKKVLAPRVN LTFRKILLTK K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human 2OG-Fe(II) oxy DC1." Lin Y., Xie Y., Mao Y. Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[3]	"Reversal of DNA alkylation damage by two human dioxygenases." Duncan T., Trewick S.C., Koivisto P., Bates P.A., Lindahl T., Sedgwick B. Proc. Natl. Acad. Sci. U.S.A. 99:16660-16665(2002) [PubMed: 12486230] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA." Aas P.A., Otterlei M., Falnes P.O., Vaagboe C.B., Skorpen F., Akbari M., Sundheim O., Bjoeraas M., Slupphaug G., Seeberg E., Krokan H.E. Nature 421:859-863(2003) [PubMed: 12594517] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]	"Repair of methylation damage in DNA and RNA by mammalian AlkB homologues." Lee D.-H., Jin S.-G., Cai S., Chen Y., Pfeifer G.P., O'Connor T.R. J. Biol. Chem. 280:39448-39459(2005) [PubMed: 16174769] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-173 AND HIS-236, TISSUE SPECIFICITY.
[6]	"AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA." Ringvoll J., Moen M.N., Nordstrand L.M., Meira L.B., Pang B., Bekkelund A., Dedon P.C., Bjelland S., Samson L.D., Falnes P.O., Klungland A. Cancer Res. 68:4142-4149(2008) [PubMed: 18519673] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, COFACTOR.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA." Yang C.G., Yi C., Duguid E.M., Sullivan C.T., Jian X., Rice P.A., He C. Nature 452:961-965(2008) [PubMed: 18432238] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-258 IN COMPLEXES WITH DS-DNA; ALPHA-KETOGLUTARATE AND METAL IONS, FUNCTION, COFACTOR.
[9]	"Structure determination of DNA methylation lesions N1-meA and N3-meC in duplex DNA using a cross-linked protein-DNA system." Lu L., Yi C., Jian X., Zheng G., He C. Nucleic Acids Res. 38:4415-4425(2010) [PubMed: 20223766] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 56-261 IN COMPLEXES WITH DOUBLE-STRANDED DNA CONTAINING 1-METHYLADENINE OR 3-METHYLCYTOSINE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY754389 mRNA. Translation: AAV28301.1.
BC070489 mRNA. Translation: AAH70489.1.

IPI

IPI00055405.

RefSeq

NP_001001655.1. NM_001001655.2.
NP_001138846.1. NM_001145374.1.
NP_001138847.1. NM_001145375.1.

UniGene

Hs.374458.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BTX	X-ray	2.00	A	56-258	[»]
3BTY	X-ray	2.35	A	56-258	[»]
3BTZ	X-ray	3.00	A	57-258	[»]
3BU0	X-ray	2.50	A	56-258	[»]
3BUC	X-ray	2.59	A	56-258	[»]
3H8O	X-ray	2.50	A	56-261	[»]
3H8R	X-ray	1.77	A	56-261	[»]
3H8X	X-ray	2.50	A	56-261	[»]

ProteinModelPortal

Q6NS38.

SMR

Q6NS38. Positions 56-258.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q6NS38. 1 interaction.

STRING

Q6NS38.

Polymorphism databases

DMDM

74736661.

Proteomic databases

PRIDE

Q6NS38.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000343075; ENSP00000343021; ENSG00000189046.
ENST00000429722; ENSP00000398181; ENSG00000189046.
ENST00000435370; ENSP00000398509; ENSG00000189046.

GeneID

121642.

KEGG

hsa:121642.

UCSC

uc001tnx.1. human.

Organism-specific databases

CTD

121642.

GeneCards

GC12M109525.

H-InvDB

HIX0036774.

HGNC

HGNC:32487. ALKBH2.

HPA

CAB011198.

MIM

610602. gene.

neXtProt

NX_Q6NS38.

PharmGKB

PA143485292.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08807.

GeneTree

ENSGT00530000063618.

HOGENOM

HBG713578.

HOVERGEN

HBG080832.

InParanoid

Q6NS38.

OMA

HRDDEKE.

OrthoDB

EOG4N8R5T.

PhylomeDB

Q6NS38.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

Q6NS38.

Bgee

Q6NS38.

CleanEx

HS_ALKBH2.

Genevestigator

Q6NS38.

GermOnline

ENSG00000189046. Homo sapiens.

Family and domain databases

InterPro

IPR005123. Oxoglutarate/Fe-dep_oxygenase.
[Graphical view]

KO

K10859.

Pfam

PF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]

PROSITE

PS51471. FE2OG_OXY. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00126. Vitamin C.

NextBio

80790.

SOURCE

Search...

Entry information

Entry name

ALKB2_HUMAN

Accession

Primary (citable) accession number: Q6NS38
Secondary accession number(s): Q5XLE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.