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Q96Q83

- ALKB3_HUMAN

UniProt

Q96Q83 - ALKB3_HUMAN

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Protein

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3

Gene

ALKBH3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.4 Publications

Cofactori

Fe2+Note: Binds 1 Fe(2+) ion per subunit.

Enzyme regulationi

Activated by ascorbate.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei115 – 1151SubstrateBy similarity
Metal bindingi191 – 1911Iron; catalytic1 PublicationPROSITE-ProRule annotation
Metal bindingi193 – 1931Iron; catalytic1 PublicationPROSITE-ProRule annotation
Binding sitei194 – 1941SubstrateBy similarity
Metal bindingi257 – 2571Iron; catalytic1 PublicationPROSITE-ProRule annotation

GO - Molecular functioni

  1. DNA-N1-methyladenine dioxygenase activity Source: UniProtKB
  2. ferrous iron binding Source: UniProtKB
  3. L-ascorbic acid binding Source: UniProtKB-KW

GO - Biological processi

  1. cell proliferation Source: UniProtKB
  2. DNA dealkylation involved in DNA repair Source: UniProtKB
  3. DNA repair Source: UniProtKB
  4. oxidative single-stranded DNA demethylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

Iron, Metal-binding, Vitamin C

Enzyme and pathway databases

ReactomeiREACT_1662. ABH3 mediated Reversal of Alkylation Damage.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ALKBH3
Synonyms:ABH3, DEPC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:30141. ALKBH3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi122 – 1221R → A: Decreases activity towards ssDNA by 25%. Loss of activity towards dsDNA.
Mutagenesisi123 – 1231E → A: Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
Mutagenesisi131 – 1311R → A: Loss of activity.
Mutagenesisi177 – 1771L → A or N: Loss of activity against 1-methyladenine.
Mutagenesisi177 – 1771L → E or Q: Loss of activity.
Mutagenesisi177 – 1771L → I: Decreases activity against 1-methyladenine.
Mutagenesisi177 – 1771L → M: No effect.
Mutagenesisi179 – 1791N → A: Decreases activity by about 60%.
Mutagenesisi181 – 1811Y → A: Strong decrease of activity.
Mutagenesisi189 – 1891D → A: Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
Mutagenesisi191 – 1911H → A: Loss of activity.
Mutagenesisi193 – 1931D → A: Loss of activity. 1 Publication
Mutagenesisi257 – 2571H → A: Decreases activity by about 65%. 2 Publications
Mutagenesisi269 – 2691R → A: Strong decrease of activity.
Mutagenesisi271 – 2711N → A: No effect.
Mutagenesisi275 – 2751R → A: Loss of activity.

Organism-specific databases

PharmGKBiPA143485293.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 286286Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3PRO_0000239278Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei177 – 1771(4R)-5-hydroxyleucine; alternate1 Publication
Modified residuei177 – 1771(4R)-5-oxoleucine; alternate1 Publication

Keywords - PTMi

Hydroxylation, Oxidation

Proteomic databases

MaxQBiQ96Q83.
PaxDbiQ96Q83.
PRIDEiQ96Q83.

PTM databases

PhosphoSiteiQ96Q83.

Expressioni

Tissue specificityi

Ubiquitous. Detected in heart, pancreas, skeletal muscle, thymus, testis, ovary, spleen, prostate, small intestine, peripheral blood leukocytes, urinary bladder and colon.3 Publications

Gene expression databases

BgeeiQ96Q83.
CleanExiHS_ALKBH3.
ExpressionAtlasiQ96Q83. baseline and differential.
GenevestigatoriQ96Q83.

Organism-specific databases

HPAiCAB005007.
HPA009674.

Interactioni

Subunit structurei

Interacts with the TRIP4 complex, notably composed of ASCC3.2 Publications

Protein-protein interaction databases

BioGridi128686. 9 interactions.
IntActiQ96Q83. 3 interactions.
STRINGi9606.ENSP00000302232.

Structurei

Secondary structure

1
286
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi74 – 818Combined sources
Beta strandi84 – 863Combined sources
Beta strandi88 – 936Combined sources
Helixi99 – 11214Combined sources
Beta strandi119 – 1246Combined sources
Beta strandi126 – 1283Combined sources
Beta strandi130 – 1378Combined sources
Helixi145 – 1484Combined sources
Beta strandi151 – 1533Combined sources
Helixi156 – 16914Combined sources
Beta strandi175 – 1817Combined sources
Beta strandi188 – 1914Combined sources
Helixi196 – 1983Combined sources
Beta strandi204 – 2118Combined sources
Beta strandi213 – 2197Combined sources
Beta strandi234 – 2396Combined sources
Beta strandi244 – 2496Combined sources
Helixi251 – 2544Combined sources
Beta strandi255 – 2595Combined sources
Beta strandi269 – 2757Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2IUWX-ray1.50A70-286[»]
ProteinModelPortaliQ96Q83.
SMRiQ96Q83. Positions 70-279.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96Q83.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini172 – 278107Fe2OG dioxygenasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni141 – 1433Substrate bindingBy similarity
Regioni179 – 1813Alpha-ketoglutarate binding
Regioni269 – 2757Alpha-ketoglutarate binding

Sequence similaritiesi

Belongs to the alkB family.Curated
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG3145.
GeneTreeiENSGT00530000063618.
HOGENOMiHOG000207105.
HOVERGENiHBG056732.
InParanoidiQ96Q83.
KOiK10860.
OMAiDRGPRIN.
PhylomeDBiQ96Q83.
TreeFamiTF331732.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
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. Align

Isoform 1 (identifier: Q96Q83-1) [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
MEEKRRRARV QGAWAAPVKS QAIAQPATTA KSHLHQKPGQ TWKNKEHHLS
60 70 80 90 100
DREFVFKEPQ QVVRRAPEPR VIDREGVYEI SLSPTGVSRV CLYPGFVDVK
110 120 130 140 150
EADWILEQLC QDVPWKQRTG IREDITYQQP RLTAWYGELP YTYSRITMEP
160 170 180 190 200
NPHWHPVLRT LKNRIEENTG HTFNSLLCNL YRNEKDSVDW HSDDEPSLGR
210 220 230 240 250
CPIIASLSFG ATRTFEMRKK PPPEENGDYT YVERVKIPLD HGTLLIMEGA
260 270 280
TQADWQHRVP KEYHSREPRV NLTFRTVYPD PRGAPW
Length:286
Mass (Da):33,375
Last modified:December 1, 2001 - v1
Checksum:iF6563635B1F217D7
GO
Isoform 2 (identifier: Q96Q83-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:170
Mass (Da):19,310
Checksum:i9BC42BA5B40B035C
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti164 – 1641R → C.1 Publication
Corresponds to variant rs2271815 [ dbSNP | Ensembl ].
VAR_026632
Natural varianti228 – 2281D → E.2 Publications
Corresponds to variant rs2434470 [ dbSNP | Ensembl ].
VAR_026631

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei73 – 742DR → E in isoform 2. 1 PublicationVSP_019125
Alternative sequencei125 – 17248ITYQQ…NTGHT → SILQLTFKKSAPVSGTATAP QSCWYERPSPPHIPGPAILT RTRLWAP in isoform 2. 1 PublicationVSP_019126Add
BLAST
Alternative sequencei173 – 286114Missing in isoform 2. 1 PublicationVSP_019127Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7906.1. [Q96Q83-1]
RefSeqiNP_631917.1. NM_139178.3. [Q96Q83-1]
UniGeneiHs.720708.

Genome annotation databases

EnsembliENST00000302708; ENSP00000302232; ENSG00000166199. [Q96Q83-1]
ENST00000530803; ENSP00000436788; ENSG00000166199. [Q96Q83-2]
GeneIDi221120.
KEGGihsa:221120.
UCSCiuc001mxs.2. human. [Q96Q83-1]

Polymorphism databases

DMDMi74752087.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS7906.1. [Q96Q83-1 ]
RefSeqi NP_631917.1. NM_139178.3. [Q96Q83-1 ]
UniGenei Hs.720708.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2IUW X-ray 1.50 A 70-286 [» ]
ProteinModelPortali Q96Q83.
SMRi Q96Q83. Positions 70-279.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 128686. 9 interactions.
IntActi Q96Q83. 3 interactions.
STRINGi 9606.ENSP00000302232.

Chemistry

ChEMBLi CHEMBL3112376.
DrugBanki DB00126. Vitamin C.

PTM databases

PhosphoSitei Q96Q83.

Polymorphism databases

DMDMi 74752087.

Proteomic databases

MaxQBi Q96Q83.
PaxDbi Q96Q83.
PRIDEi Q96Q83.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000302708 ; ENSP00000302232 ; ENSG00000166199 . [Q96Q83-1 ]
ENST00000530803 ; ENSP00000436788 ; ENSG00000166199 . [Q96Q83-2 ]
GeneIDi 221120.
KEGGi hsa:221120.
UCSCi uc001mxs.2. human. [Q96Q83-1 ]

Organism-specific databases

CTDi 221120.
GeneCardsi GC11P043902.
HGNCi HGNC:30141. ALKBH3.
HPAi CAB005007.
HPA009674.
MIMi 610603. gene.
neXtProti NX_Q96Q83.
PharmGKBi PA143485293.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG3145.
GeneTreei ENSGT00530000063618.
HOGENOMi HOG000207105.
HOVERGENi HBG056732.
InParanoidi Q96Q83.
KOi K10860.
OMAi DRGPRIN.
PhylomeDBi Q96Q83.
TreeFami TF331732.

Enzyme and pathway databases

Reactomei REACT_1662. ABH3 mediated Reversal of Alkylation Damage.

Miscellaneous databases

ChiTaRSi ALKBH3. human.
EvolutionaryTracei Q96Q83.
GenomeRNAii 221120.
NextBioi 91204.
PROi Q96Q83.
SOURCEi Search...

Gene expression databases

Bgeei Q96Q83.
CleanExi HS_ALKBH3.
ExpressionAtlasi Q96Q83. baseline and differential.
Genevestigatori Q96Q83.

Family and domain databases

Gene3Di 2.60.120.590. 1 hit.
InterProi IPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view ]
Pfami PF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view ]
PROSITEi PS51471. FE2OG_OXY. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. 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. 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. 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, HYDROXYLATION AT LEU-177, OXIDATION AT LEU-177.

Entry informationi

Entry nameiALKB3_HUMAN
AccessioniPrimary (citable) accession number: Q96Q83
Secondary accession number(s): A6NDJ1
, Q3SYI0, Q6NX57, Q96BU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: December 1, 2001
Last modified: November 26, 2014
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 11
    Human chromosome 11: 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

External Data

Dasty 3