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Protein

DNA oxidative demethylase ALKBH2

Gene

ALKBH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.5 Publications

Catalytic activityi

DNA-base-CH3 + 2-oxoglutarate + O2 = DNA-base + formaldehyde + succinate + CO2.

Cofactori

Fe2+PROSITE-ProRule annotation2 PublicationsNote: Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation2 Publications

Activity regulationi

Activated by ascorbate and magnesium ions.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi171Iron; catalytic1 Publication1
Metal bindingi173Iron; catalytic1 Publication1
Binding sitei174Substrate1 Publication1
Metal bindingi236Iron; catalytic1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
Biological processDNA damage, DNA repair
LigandIron, Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.11.33 2681
ReactomeiR-HSA-112122 ALKBH2 mediated reversal of alkylation damage

Names & Taxonomyi

Protein namesi
Recommended name:
DNA oxidative demethylase ALKBH2 (EC:1.14.11.33)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 2
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2
Oxy DC1
Gene namesi
Name:ALKBH2
Synonyms:ABH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000189046.10
HGNCiHGNC:32487 ALKBH2
MIMi610602 gene
neXtProtiNX_Q6NS38

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi173D → A: Loss of activity. 1 Publication1
Mutagenesisi236H → A: Reduced activity. 1 Publication1

Organism-specific databases

DisGeNETi121642
OpenTargetsiENSG00000189046
PharmGKBiPA143485292

Chemistry databases

DrugBankiDB00126 Vitamin C

Polymorphism and mutation databases

BioMutaiALKBH2
DMDMi74736661

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002392751 – 261DNA oxidative demethylase ALKBH2Add BLAST261

Proteomic databases

EPDiQ6NS38
MaxQBiQ6NS38
PaxDbiQ6NS38
PeptideAtlasiQ6NS38
PRIDEiQ6NS38
ProteomicsDBi66621
66622 [Q6NS38-2]

PTM databases

iPTMnetiQ6NS38
PhosphoSitePlusiQ6NS38

Expressioni

Tissue specificityi

Detected in colon, small intestine, ovary, testis, prostate, skeletal muscle, heart, liver and urinary bladder.2 Publications

Gene expression databases

BgeeiENSG00000189046 Expressed in 167 organ(s), highest expression level in prostate gland
CleanExiHS_ALKBH2
ExpressionAtlasiQ6NS38 baseline and differential
GenevisibleiQ6NS38 HS

Organism-specific databases

HPAiCAB011198
HPA045392
HPA051976

Interactioni

Protein-protein interaction databases

BioGridi125741, 12 interactors
IntActiQ6NS38, 7 interactors
STRINGi9606.ENSP00000343021

Structurei

Secondary structure

1261
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6NS38
SMRiQ6NS38
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ6NS38

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini152 – 257Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST106

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni102 – 104Substrate binding1 Publication3
Regioni122 – 124Substrate binding1 Publication3
Regioni159 – 161Alpha-ketoglutarate binding1 Publication3
Regioni248 – 254Alpha-ketoglutarate binding1 Publication7

Sequence similaritiesi

Belongs to the alkB family.Curated

Phylogenomic databases

eggNOGiENOG410IIVX Eukaryota
COG3145 LUCA
GeneTreeiENSGT00530000063618
HOGENOMiHOG000263606
HOVERGENiHBG080832
InParanoidiQ6NS38
KOiK10859
OMAiQATYGDT
OrthoDBiEOG091G0S0P
PhylomeDBiQ6NS38
TreeFamiTF331732

Family and domain databases

Gene3Di2.60.120.590, 1 hit
InterProiView protein in InterPro
IPR027450 AlkB-like
IPR037151 AlkB-like_sf
IPR005123 Oxoglu/Fe-dep_dioxygenase
PfamiView protein in Pfam
PF13532 2OG-FeII_Oxy_2, 1 hit
PROSITEiView protein in PROSITE
PS51471 FE2OG_OXY, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q6NS38-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDRFLVKGAQ GGLLRKQEEQ EPTGEEPAVL GGDKESTRKR PRREAPGNGG
60 70 80 90 100
HSAGPSWRHI RAEGLDCSYT VLFGKAEADE IFQELEKEVE YFTGALARVQ
110 120 130 140 150
VFGKWHSVPR KQATYGDAGL TYTFSGLTLS PKPWIPVLER IRDHVSGVTG
160 170 180 190 200
QTFNFVLINR YKDGCDHIGE HRDDERELAP GSPIASVSFG ACRDFVFRHK
210 220 230 240 250
DSRGKSPSRR VAVVRLPLAH GSLLMMNHPT NTHWYHSLPV RKKVLAPRVN
260
LTFRKILLTK K
Length:261
Mass (Da):29,322
Last modified:July 5, 2004 - v1
Checksum:iA376E13F92621A01
GO
Isoform 2 (identifier: Q6NS38-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     95-261: ALARVQVFGK...TFRKILLTKK → IKMAVTTSGS...SGCRWPTGAY

Note: No experimental confirmation available.
Show »
Length:157
Mass (Da):17,083
Checksum:iCB86433F4323248A
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H5X2F5H5X2_HUMAN
DNA oxidative demethylase ALKBH2
ALKBH2
150Annotation score:
S4R3T5S4R3T5_HUMAN
DNA oxidative demethylase ALKBH2
ALKBH2
149Annotation score:
F5GZZ0F5GZZ0_HUMAN
DNA oxidative demethylase ALKBH2
ALKBH2
121Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti43R → G in AAV28301 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048223203R → H. Corresponds to variant dbSNP:rs33962311Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04292395 – 261ALARV…LLTKK → IKMAVTTSGSTEMMKENWPL GAPLPLSPSVPAETLSSGIR IPVGKAPPGGWRWSGCRWPT GAY in isoform 2. 1 PublicationAdd BLAST167

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY754389 mRNA Translation: AAV28301.1
AB277859 mRNA Translation: BAF56576.1
AC011596 Genomic DNA No translation available.
BC070489 mRNA Translation: AAH70489.1
CCDSiCCDS31897.1 [Q6NS38-1]
CCDS55883.1 [Q6NS38-2]
RefSeqiNP_001001655.1, NM_001001655.2 [Q6NS38-1]
NP_001138846.1, NM_001145374.1 [Q6NS38-1]
NP_001138847.1, NM_001145375.1 [Q6NS38-1]
NP_001192108.1, NM_001205179.1 [Q6NS38-2]
NP_001192109.1, NM_001205180.1 [Q6NS38-2]
XP_005253892.1, XM_005253835.4 [Q6NS38-1]
XP_005253893.1, XM_005253836.1 [Q6NS38-2]
UniGeneiHs.374458

Genome annotation databases

EnsembliENST00000343075; ENSP00000343021; ENSG00000189046 [Q6NS38-1]
ENST00000429722; ENSP00000398181; ENSG00000189046 [Q6NS38-1]
ENST00000440112; ENSP00000399820; ENSG00000189046 [Q6NS38-2]
ENST00000619381; ENSP00000478765; ENSG00000189046 [Q6NS38-2]
GeneIDi121642
KEGGihsa:121642
UCSCiuc001tnx.3 human [Q6NS38-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiALKB2_HUMAN
AccessioniPrimary (citable) accession number: Q6NS38
Secondary accession number(s): A4PET2, Q5XLE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: July 5, 2004
Last modified: September 12, 2018
This is version 124 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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