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Q96Q83 (ALKB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3

EC=1.14.11.-
Alternative name(s):
Alkylated DNA repair protein alkB homolog 3
DEPC-1
Prostate cancer antigen 1
Gene names
Name:ALKBH3
Synonyms:ABH3, DEPC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length286 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dioxygenase that repairs alkylated DNA containing 1-methyladenine (1meA) and 3-methylcytosine (3meC) by oxidative demethylation. Has a strong preference for single-stranded DNA. Able to process alkylated 3mC within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKHB3. May also act on RNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Ref.6 Ref.7 Ref.8 Ref.10

Cofactor

Binds 1 Fe2+ ion per subunit.

Enzyme regulation

Activated by ascorbate. Ref.6

Subunit structure

Interacts with the TRIP4 complex, notably composed of ASCC3. Ref.10

Subcellular location

Cytoplasm. Nucleus Ref.6 Ref.7 Ref.9.

Tissue specificity

Ubiquitous. Detected in heart, pancreas, skeletal muscle, thymus, testis, ovary, spleen, prostate, small intestine, peripheral blood leukocytes, urinary bladder and colon. Ref.6 Ref.8 Ref.9

Sequence similarities

Belongs to the alkB family.

Contains 1 Fe2OG dioxygenase domain.

Sequence caution

The sequence AAH15155.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96Q83-1)

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: Q96Q83-2)

The sequence of this isoform differs from the canonical sequence as follows:
     73-74: DR → E
     125-172: ITYQQPRLTA...NRIEENTGHT → SILQLTFKKS...ILTRTRLWAP
     173-286: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 286286Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3
PRO_0000239278

Regions

Domain172 – 278107Fe2OG dioxygenase
Region141 – 1433Substrate binding By similarity
Region179 – 1813Alpha-ketoglutarate binding
Region269 – 2757Alpha-ketoglutarate binding

Sites

Metal binding1911Iron; catalytic
Metal binding1931Iron; catalytic
Metal binding2571Iron; catalytic
Binding site1151Substrate By similarity
Binding site1941Substrate By similarity
Site1771Susceptible to oxidation

Natural variations

Alternative sequence73 – 742DR → E in isoform 2.
VSP_019125
Alternative sequence125 – 17248ITYQQ…NTGHT → SILQLTFKKSAPVSGTATAP QSCWYERPSPPHIPGPAILT RTRLWAP in isoform 2.
VSP_019126
Alternative sequence173 – 286114Missing in isoform 2.
VSP_019127
Natural variant1641R → C. Ref.2
Corresponds to variant rs2271815 [ dbSNP | Ensembl ].
VAR_026632
Natural variant2281D → E. Ref.2 Ref.5
Corresponds to variant rs2434470 [ dbSNP | Ensembl ].
VAR_026631

Experimental info

Mutagenesis1221R → A: Decreases activity towards ssDNA by 25%. Loss of activity towards dsDNA.
Mutagenesis1231E → A: Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
Mutagenesis1311R → A: Loss of activity.
Mutagenesis1771L → A or N: Loss of activity against 1-methyladenine.
Mutagenesis1771L → E or Q: Loss of activity.
Mutagenesis1771L → I: Decreases activity against 1-methyladenine.
Mutagenesis1771L → M: No effect.
Mutagenesis1791N → A: Decreases activity by about 60%.
Mutagenesis1811Y → A: Strong decrease of activity.
Mutagenesis1891D → A: Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
Mutagenesis1911H → A: Loss of activity.
Mutagenesis1931D → A: Loss of activity. Ref.8
Mutagenesis2571H → A: Decreases activity by about 65%. Ref.8 Ref.10
Mutagenesis2691R → A: Strong decrease of activity.
Mutagenesis2711N → A: No effect.
Mutagenesis2751R → A: Loss of activity.

Secondary structure

........................................ 286
Helix Strand Turn

Details...

Sequences

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

Last modified December 1, 2001. Version 1.
Checksum: F6563635B1F217D7

FASTA28633,375
        10         20         30         40         50         60 
MEEKRRRARV QGAWAAPVKS QAIAQPATTA KSHLHQKPGQ TWKNKEHHLS DREFVFKEPQ 

        70         80         90        100        110        120 
QVVRRAPEPR VIDREGVYEI SLSPTGVSRV CLYPGFVDVK EADWILEQLC QDVPWKQRTG 

       130        140        150        160        170        180 
IREDITYQQP RLTAWYGELP YTYSRITMEP NPHWHPVLRT LKNRIEENTG HTFNSLLCNL 

       190        200        210        220        230        240 
YRNEKDSVDW HSDDEPSLGR CPIIASLSFG ATRTFEMRKK PPPEENGDYT YVERVKIPLD 

       250        260        270        280 
HGTLLIMEGA TQADWQHRVP KEYHSREPRV NLTFRTVYPD PRGAPW 

« Hide

Isoform 2 [UniParc].

Checksum: 9BC42BA5B40B035C
Show »

FASTA17019,310

References

« Hide 'large scale' references
[1]"Homo sapiens mRNA expressed in prostate cancer and thymus."
Tsujikawa K., Konishi N., Ono Y., Ichijou T., Sakamoto K., Yamamoto H.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal thymus and Prostatic carcinoma.
[2]NIEHS SNPs program
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-164 AND GLU-228.
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORMS 1 AND 2), VARIANT GLU-228.
Tissue: Lung and PNS.
[6]"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.
[7]"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.
[8]"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-193 AND HIS-257, TISSUE SPECIFICITY.
[9]"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]"DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation."
Dango S., Mosammaparast N., Sowa M.E., Xiong L.J., Wu F., Park K., Rubin M., Gygi S., Harper J.W., Shi Y.
Mol. Cell 44:373-384(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ALKBH3, MUTAGENESIS OF HIS-257.
[11]"Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage."
Sundheim O., Vaagboe C.B., Bjoeraas M., Sousa M.M.L., Talstad V., Aas P.A., Drabloes F., Krokan H.E., Tainer J.A., Slupphaug G.
EMBO J. 25:3389-3397(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 70-286 IN COMPLEX WITH ALPHA-KETOGLUTARATE AND IRON, IDENTIFICATION BY MASS SPECTROMETRY, OXIDATION AT LEU-177.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB042029 mRNA. Translation: BAB70508.1.
DQ196343 Genomic DNA. Translation: ABA27096.1.
AC087521 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68078.1.
BC015155 mRNA. Translation: AAH15155.1. Different initiation.
BC103812 mRNA. Translation: AAI03813.1.
BC103813 mRNA. Translation: AAI03814.1.
BC103814 mRNA. Translation: AAI03815.1.
BC067257 mRNA. Translation: AAH67257.1.
CCDSCCDS7906.1. [Q96Q83-1]
RefSeqNP_631917.1. NM_139178.3. [Q96Q83-1]
UniGeneHs.720708.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IUWX-ray1.50A70-286[»]
ProteinModelPortalQ96Q83.
SMRQ96Q83. Positions 70-279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128686. 2 interactions.
IntActQ96Q83. 3 interactions.
STRING9606.ENSP00000302232.

Chemistry

DrugBankDB00126. Vitamin C.

PTM databases

PhosphoSiteQ96Q83.

Polymorphism databases

DMDM74752087.

Proteomic databases

MaxQBQ96Q83.
PaxDbQ96Q83.
PRIDEQ96Q83.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302708; ENSP00000302232; ENSG00000166199. [Q96Q83-1]
ENST00000378840; ENSP00000368117; ENSG00000166199. [Q96Q83-2]
ENST00000530803; ENSP00000436788; ENSG00000166199. [Q96Q83-2]
GeneID221120.
KEGGhsa:221120.
UCSCuc001mxs.2. human. [Q96Q83-1]

Organism-specific databases

CTD221120.
GeneCardsGC11P043859.
HGNCHGNC:30141. ALKBH3.
HPACAB005007.
HPA009674.
MIM610603. gene.
neXtProtNX_Q96Q83.
PharmGKBPA143485293.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3145.
HOGENOMHOG000207105.
HOVERGENHBG056732.
InParanoidQ96Q83.
KOK10860.
OMADRGPRIN.
PhylomeDBQ96Q83.
TreeFamTF331732.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressQ96Q83.
BgeeQ96Q83.
CleanExHS_ALKBH3.
GenevestigatorQ96Q83.

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

EvolutionaryTraceQ96Q83.
GenomeRNAi221120.
NextBio91204.
PROQ96Q83.
SOURCESearch...

Entry information

Entry nameALKB3_HUMAN
AccessionPrimary (citable) accession number: Q96Q83
Secondary accession number(s): A6NDJ1 expand/collapse secondary AC list , Q3SYI0, Q6NX57, Q96BU8
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 113 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 11

Human chromosome 11: entries, gene names and cross-references to MIM