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Protein

DNA oxidative demethylase ALKBH2

Gene

ALKBH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

  • 1-ethyladenine demethylase activity Source: UniProtKB-EC
  • cytosine C-5 DNA demethylase activity Source: UniProtKB
  • DNA-N1-methyladenine dioxygenase activity Source: UniProtKB
  • ferrous iron binding Source: UniProtKB

GO - Biological processi

  • DNA dealkylation involved in DNA repair Source: UniProtKB
  • DNA demethylation Source: BHF-UCL
  • oxidative demethylation Source: BHF-UCL
  • oxidative DNA demethylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

Iron, 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

HGNCiHGNC:32487. ALKBH2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

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.
CleanExiHS_ALKBH2.
ExpressionAtlasiQ6NS38. baseline and differential.
GenevisibleiQ6NS38. HS.

Organism-specific databases

HPAiCAB011198.
HPA045392.
HPA051976.

Interactioni

Protein-protein interaction databases

BioGridi125741. 11 interactors.
IntActiQ6NS38. 7 interactors.
STRINGi9606.ENSP00000343021.

Structurei

Secondary structure

1261
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi58 – 62Combined sources5
Beta strandi65 – 71Combined sources7
Helixi75 – 88Combined sources14
Helixi94 – 97Combined sources4
Beta strandi98 – 101Combined sources4
Beta strandi104 – 107Combined sources4
Beta strandi109 – 116Combined sources8
Beta strandi122 – 124Combined sources3
Beta strandi127 – 129Combined sources3
Helixi136 – 149Combined sources14
Beta strandi154 – 163Combined sources10
Beta strandi168 – 171Combined sources4
Beta strandi176 – 178Combined sources3
Beta strandi184 – 191Combined sources8
Beta strandi193 – 199Combined sources7
Helixi200 – 202Combined sources3
Beta strandi204 – 206Combined sources3
Beta strandi214 – 218Combined sources5
Beta strandi222 – 227Combined sources6
Helixi230 – 233Combined sources4
Beta strandi234 – 238Combined sources5
Beta strandi248 – 254Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BTXX-ray2.00A56-258[»]
3BTYX-ray2.35A56-258[»]
3BTZX-ray3.00A57-258[»]
3BU0X-ray2.50A56-258[»]
3BUCX-ray2.59A56-258[»]
3H8OX-ray2.50A56-261[»]
3H8RX-ray1.77A56-261[»]
3H8XX-ray2.50A56-261[»]
3RZGX-ray1.62A56-261[»]
3RZHX-ray2.25A56-261[»]
3RZJX-ray2.50A56-261[»]
3RZKX-ray2.78A56-261[»]
3RZLX-ray2.60A/D56-261[»]
3RZMX-ray3.06A56-260[»]
3S57X-ray1.60A56-258[»]
3S5AX-ray1.70A56-258[»]
4MG2X-ray2.30A56-258[»]
4MGTX-ray2.60A56-258[»]
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
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

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.
InterProiIPR027450. AlkB-like.
IPR032852. ALKBH2.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PANTHERiPTHR31573. PTHR31573. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 rs33962311dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BTXX-ray2.00A56-258[»]
3BTYX-ray2.35A56-258[»]
3BTZX-ray3.00A57-258[»]
3BU0X-ray2.50A56-258[»]
3BUCX-ray2.59A56-258[»]
3H8OX-ray2.50A56-261[»]
3H8RX-ray1.77A56-261[»]
3H8XX-ray2.50A56-261[»]
3RZGX-ray1.62A56-261[»]
3RZHX-ray2.25A56-261[»]
3RZJX-ray2.50A56-261[»]
3RZKX-ray2.78A56-261[»]
3RZLX-ray2.60A/D56-261[»]
3RZMX-ray3.06A56-260[»]
3S57X-ray1.60A56-258[»]
3S5AX-ray1.70A56-258[»]
4MG2X-ray2.30A56-258[»]
4MGTX-ray2.60A56-258[»]
ProteinModelPortaliQ6NS38.
SMRiQ6NS38.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125741. 11 interactors.
IntActiQ6NS38. 7 interactors.
STRINGi9606.ENSP00000343021.

Chemistry databases

DrugBankiDB00126. Vitamin C.

PTM databases

iPTMnetiQ6NS38.
PhosphoSitePlusiQ6NS38.

Polymorphism and mutation databases

BioMutaiALKBH2.
DMDMi74736661.

Proteomic databases

EPDiQ6NS38.
MaxQBiQ6NS38.
PaxDbiQ6NS38.
PeptideAtlasiQ6NS38.
PRIDEiQ6NS38.

Protocols and materials databases

DNASUi121642.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi121642.
DisGeNETi121642.
GeneCardsiALKBH2.
HGNCiHGNC:32487. ALKBH2.
HPAiCAB011198.
HPA045392.
HPA051976.
MIMi610602. gene.
neXtProtiNX_Q6NS38.
OpenTargetsiENSG00000189046.
PharmGKBiPA143485292.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiQ6NS38.
GenomeRNAii121642.
PROiQ6NS38.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000189046.
CleanExiHS_ALKBH2.
ExpressionAtlasiQ6NS38. baseline and differential.
GenevisibleiQ6NS38. HS.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032852. ALKBH2.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PANTHERiPTHR31573. PTHR31573. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALKB2_HUMAN
AccessioniPrimary (citable) accession number: Q6NS38
Secondary accession number(s): A4PET2, Q5XLE3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 117 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.