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Q6NS38 (ALKB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2

EC=1.14.11.33
Alternative name(s):
Alkylated DNA repair protein alkB homolog 2
DNA oxidative demethylase ALKBH2
Oxy DC1
Gene names
Name:ALKBH2
Synonyms:ABH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Protein existenceEvidence 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.5 Ref.6 Ref.7 Ref.8 Ref.10

Catalytic activity

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

Cofactor

Binds 1 Fe2+ ion per subunit. Ref.8 Ref.10

Enzyme regulation

Activated by ascorbate and magnesium ions. Ref.5 Ref.8

Subcellular location

Nucleus. Note: Detected in replication foci during S-phase. Ref.5 Ref.6

Tissue specificity

Detected in colon, small intestine, ovary, testis, prostate, skeletal muscle, heart, liver and urinary bladder. Ref.5 Ref.7

Sequence similarities

Belongs to the alkB family.

Contains 1 Fe2OG dioxygenase domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6NS38-1)

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.
Isoform 2 (identifier: Q6NS38-2)

The sequence of this isoform differs from the canonical sequence as follows:
     95-261: ALARVQVFGK...TFRKILLTKK → IKMAVTTSGS...SGCRWPTGAY
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 261261Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2
PRO_0000239275

Regions

Domain152 – 257106Fe2OG dioxygenase
Region102 – 1043Substrate binding
Region122 – 1243Substrate binding
Region159 – 1613Alpha-ketoglutarate binding
Region248 – 2547Alpha-ketoglutarate binding

Sites

Metal binding1711Iron; catalytic
Metal binding1731Iron; catalytic
Metal binding2361Iron; catalytic
Binding site1741Substrate

Natural variations

Alternative sequence95 – 261167ALARV…LLTKK → IKMAVTTSGSTEMMKENWPL GAPLPLSPSVPAETLSSGIR IPVGKAPPGGWRWSGCRWPT GAY in isoform 2.
VSP_042923
Natural variant2031R → H.
Corresponds to variant rs33962311 [ dbSNP | Ensembl ].
VAR_048223

Experimental info

Mutagenesis1731D → A: Loss of activity. Ref.7
Mutagenesis2361H → A: Reduced activity. Ref.7
Sequence conflict431R → G in AAV28301. Ref.1

Secondary structure

.......................................... 261
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: A376E13F92621A01

FASTA26129,322
        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 

« Hide

Isoform 2 [UniParc].

Checksum: CB86433F4323248A
Show »

FASTA15717,083

References

« Hide '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] (ISOFORM 1).
[2]"Expression and sub-cellular localization of human ABH family molecules."
Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H.
J. Cell. Mol. Med. 11:1105-1116(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Testis.
[3]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Skin.
[5]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-173 AND HIS-236, TISSUE SPECIFICITY.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, COFACTOR.
[9]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-258 IN COMPLEXES WITH DS-DNA; ALPHA-KETOGLUTARATE AND METAL IONS, FUNCTION, COFACTOR.
[11]"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] [Europe PMC] [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.
AB277859 mRNA. Translation: BAF56576.1.
AC011596 Genomic DNA. No translation available.
BC070489 mRNA. Translation: AAH70489.1.
RefSeqNP_001001655.1. NM_001001655.2.
NP_001138846.1. NM_001145374.1.
NP_001138847.1. NM_001145375.1.
NP_001192108.1. NM_001205179.1.
NP_001192109.1. NM_001205180.1.
XP_005253892.1. XM_005253835.2.
XP_005253893.1. XM_005253836.1.
UniGeneHs.374458.

3D structure databases

PDBe
RCSB PDB
PDBj
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-ray3.06A56-259[»]
3S57X-ray1.60A56-258[»]
3S5AX-ray1.70A56-258[»]
4MG2X-ray2.30A56-258[»]
4MGTX-ray2.60A56-258[»]
ProteinModelPortalQ6NS38.
SMRQ6NS38. Positions 56-258.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125741. 2 interactions.
IntActQ6NS38. 1 interaction.
STRING9606.ENSP00000343021.

Chemistry

DrugBankDB00126. Vitamin C.

PTM databases

PhosphoSiteQ6NS38.

Polymorphism databases

DMDM74736661.

Proteomic databases

PaxDbQ6NS38.
PRIDEQ6NS38.

Protocols and materials databases

DNASU121642.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000343075; ENSP00000343021; ENSG00000189046. [Q6NS38-1]
ENST00000429722; ENSP00000398181; ENSG00000189046. [Q6NS38-1]
ENST00000440112; ENSP00000399820; ENSG00000189046. [Q6NS38-2]
GeneID121642.
KEGGhsa:121642.
UCSCuc001tnx.2. human. [Q6NS38-1]
uc009zvd.2. human. [Q6NS38-2]

Organism-specific databases

CTD121642.
GeneCardsGC12M109525.
HGNCHGNC:32487. ALKBH2.
HPACAB011198.
MIM610602. gene.
neXtProtNX_Q6NS38.
PharmGKBPA143485292.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3145.
HOGENOMHOG000263606.
HOVERGENHBG080832.
InParanoidQ6NS38.
KOK10859.
OMAHRDDEKE.
OrthoDBEOG77T159.
PhylomeDBQ6NS38.
TreeFamTF331732.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressQ6NS38.
BgeeQ6NS38.
CleanExHS_ALKBH2.
GenevestigatorQ6NS38.

Family and domain databases

Gene3D2.60.120.590. 1 hit.
InterProIPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
PROSITEPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ6NS38.
GenomeRNAi121642.
NextBio80790.
PROQ6NS38.
SOURCESearch...

Entry information

Entry nameALKB2_HUMAN
AccessionPrimary (citable) accession number: Q6NS38
Secondary accession number(s): A4PET2, Q5XLE3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM