Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3

Gene

ALKBH3

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

Functioni

Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A) (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410). Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:12486230, PubMed:12594517, PubMed:16174769). Has a strong preference for single-stranded DNA (PubMed:12486230, PubMed:12594517, PubMed:16174769). Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3 (PubMed:22055184). Also acts on RNA (PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410, PubMed:16858410). Demethylates N(1)-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5'-untranslated regions (UTRs) and in the vicinity of start codons (PubMed:26863196, PubMed:26863410). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:22055184, PubMed:16858410).7 Publications

Catalytic activityi

N(1)-methyladenosine in mRNA + 2-oxoglutarate + O2 = adenosine in mRNA + formaldehyde + succinate + CO2.1 Publication

Cofactori

Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication

Enzyme regulationi

Activated by ascorbate.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei115 – 1151SubstrateBy similarity
Metal bindingi191 – 1911Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi193 – 1931Iron; catalyticPROSITE-ProRule annotation1 Publication
Binding sitei194 – 1941SubstrateBy similarity
Metal bindingi257 – 2571Iron; catalyticPROSITE-ProRule annotation1 Publication

GO - Molecular functioni

  • cytosine C-5 DNA demethylase activity Source: Ensembl
  • DNA-N1-methyladenine dioxygenase activity Source: UniProtKB
  • ferrous iron binding Source: UniProtKB
  • L-ascorbic acid binding Source: UniProtKB-KW
  • RNA N1-methyladenosine dioxygenase activity Source: UniProtKB

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • DNA dealkylation involved in DNA repair Source: UniProtKB
  • DNA repair Source: UniProtKB
  • oxidative single-stranded DNA demethylation Source: UniProtKB
  • oxidative single-stranded RNA 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

BRENDAi1.14.11.33. 2681.
ReactomeiR-HSA-112126. ALKBH3 mediated reversal of alkylation damage.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3Curated (EC:1.14.11.-1 Publication2 Publications)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 31 Publication
Short name:
hABH31 Publication
DEPC-11 Publication
Prostate cancer antigen 11 Publication
Gene namesi
Name:ALKBH3
Synonyms:ABH31 Publication, DEPC11 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:30141. ALKBH3.

Subcellular locationi

GO - Cellular componenti

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. 2 Publications
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.

Chemistry

ChEMBLiCHEMBL3112376.
DrugBankiDB00126. Vitamin C.

Polymorphism and mutation databases

BioMutaiALKBH3.
DMDMi74752087.

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

EPDiQ96Q83.
MaxQBiQ96Q83.
PaxDbiQ96Q83.
PeptideAtlasiQ96Q83.
PRIDEiQ96Q83.

PTM databases

iPTMnetiQ96Q83.
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

BgeeiENSG00000166199.
CleanExiHS_ALKBH3.
ExpressionAtlasiQ96Q83. baseline and differential.
GenevisibleiQ96Q83. HS.

Organism-specific databases

HPAiCAB005007.
HPA009674.
HPA046489.

Interactioni

Subunit structurei

Interacts with the ASC-1 complex, notably composed of ASCC3 (PubMed:22055184).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AK8Q96MA63EBI-6658697,EBI-8466265
GLRX3O760033EBI-6658697,EBI-374781
GOLGA2Q083793EBI-6658697,EBI-618309
IKZF1Q134223EBI-6658697,EBI-745305
LNX1Q8TBB13EBI-6658697,EBI-739832

Protein-protein interaction databases

BioGridi128686. 49 interactions.
IntActiQ96Q83. 8 interactions.
STRINGi9606.ENSP00000302232.

Chemistry

BindingDBiQ96Q83.

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 binding1 Publication
Regioni269 – 2757Alpha-ketoglutarate binding1 Publication

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IETS. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00530000063618.
HOGENOMiHOG000207105.
HOVERGENiHBG056732.
InParanoidiQ96Q83.
KOiK10860.
OMAiHWHPVLS.
OrthoDBiEOG091G0S0P.
PhylomeDBiQ96Q83.
TreeFamiTF331732.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032854. ALKBH3.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PANTHERiPTHR31212. PTHR31212. 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: 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 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.3. human. [Q96Q83-1]

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.
CCDSiCCDS7906.1. [Q96Q83-1]
RefSeqiNP_631917.1. NM_139178.3. [Q96Q83-1]
UniGeneiHs.720708.

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...

Protein-protein interaction databases

BioGridi128686. 49 interactions.
IntActiQ96Q83. 8 interactions.
STRINGi9606.ENSP00000302232.

Chemistry

BindingDBiQ96Q83.
ChEMBLiCHEMBL3112376.
DrugBankiDB00126. Vitamin C.

PTM databases

iPTMnetiQ96Q83.
PhosphoSiteiQ96Q83.

Polymorphism and mutation databases

BioMutaiALKBH3.
DMDMi74752087.

Proteomic databases

EPDiQ96Q83.
MaxQBiQ96Q83.
PaxDbiQ96Q83.
PeptideAtlasiQ96Q83.
PRIDEiQ96Q83.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302708; ENSP00000302232; ENSG00000166199. [Q96Q83-1]
ENST00000530803; ENSP00000436788; ENSG00000166199. [Q96Q83-2]
GeneIDi221120.
KEGGihsa:221120.
UCSCiuc001mxs.3. human. [Q96Q83-1]

Organism-specific databases

CTDi221120.
GeneCardsiALKBH3.
HGNCiHGNC:30141. ALKBH3.
HPAiCAB005007.
HPA009674.
HPA046489.
MIMi610603. gene.
neXtProtiNX_Q96Q83.
PharmGKBiPA143485293.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IETS. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00530000063618.
HOGENOMiHOG000207105.
HOVERGENiHBG056732.
InParanoidiQ96Q83.
KOiK10860.
OMAiHWHPVLS.
OrthoDBiEOG091G0S0P.
PhylomeDBiQ96Q83.
TreeFamiTF331732.

Enzyme and pathway databases

BRENDAi1.14.11.33. 2681.
ReactomeiR-HSA-112126. ALKBH3 mediated reversal of alkylation damage.

Miscellaneous databases

ChiTaRSiALKBH3. human.
EvolutionaryTraceiQ96Q83.
GenomeRNAii221120.
PROiQ96Q83.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166199.
CleanExiHS_ALKBH3.
ExpressionAtlasiQ96Q83. baseline and differential.
GenevisibleiQ96Q83. HS.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032854. ALKBH3.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PANTHERiPTHR31212. PTHR31212. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: September 7, 2016
This is version 134 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

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.