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Protein

RNA demethylase ALKBH5

Gene

Alkbh5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (By similarity). Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA processing and export (By similarity). Required for spermatogenesis (PubMed:23177736).By similarity1 Publication

Catalytic activityi

N(6)-methyladenosine in mRNA + 2-oxoglutarate + O2 = adenosine in mRNA + formaldehyde + succinate + CO2.By similarity

Cofactori

Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi205Iron; catalyticBy similarity1
Metal bindingi207Iron; catalyticBy similarity1
Metal bindingi267Iron; catalyticBy similarity1
Binding sitei278Alpha-ketoglutarateBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Differentiation, Spermatogenesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-73943. Reversal of alkylation damage by DNA dioxygenases.

Names & Taxonomyi

Protein namesi
Recommended name:
RNA demethylase ALKBH5 (EC:1.14.11.-By similarity)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 5
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5
Gene namesi
Name:Alkbh5
Synonyms:Abh5, Ofoxd
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2144489. Alkbh5.

Subcellular locationi

  • Nucleus speckle By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are viable, anatomically normal and reach adulthood but display impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. Male mice have increased m6A in mRNA. Testes are significantly smaller and histological analysis of testis sections reveal aberrant tubular architecture and size. The number of spermatozoa released from cauda epididymes is dramatically reduced, and the spermatozoa are morphologically abnormal with greatly compromised motility.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002392842 – 395RNA demethylase ALKBH5Add BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei65PhosphoserineCombined sources1
Modified residuei70PhosphoserineBy similarity1
Modified residuei72PhosphotyrosineBy similarity1
Modified residuei133N6-acetyllysineBy similarity1
Modified residuei360Omega-N-methylarginineBy similarity1
Modified residuei362PhosphoserineCombined sources1
Modified residuei372PhosphoserineCombined sources1
Modified residuei375PhosphoserineBy similarity1
Modified residuei385PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ3TSG4.
MaxQBiQ3TSG4.
PaxDbiQ3TSG4.
PeptideAtlasiQ3TSG4.
PRIDEiQ3TSG4.

PTM databases

iPTMnetiQ3TSG4.
PhosphoSitePlusiQ3TSG4.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000042650.
CleanExiMM_ALKBH5.
GenevisibleiQ3TSG4. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000049116.

Structurei

3D structure databases

ProteinModelPortaliQ3TSG4.
SMRiQ3TSG4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni194 – 196Alpha-ketoglutarate bindingBy similarity3

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili68 – 117Sequence analysisAdd BLAST50

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi30 – 48Ala-richAdd BLAST19

Sequence similaritiesi

Belongs to the alkB family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410INB3. Eukaryota.
ENOG410Y0IS. LUCA.
GeneTreeiENSGT00390000009298.
HOGENOMiHOG000007505.
HOVERGENiHBG080833.
InParanoidiQ3TSG4.
KOiK10767.
OMAiWVHELVI.
OrthoDBiEOG091G0KLO.
PhylomeDBiQ3TSG4.
TreeFamiTF329212.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032860. ALKBH5.
[Graphical view]
PANTHERiPTHR32074. PTHR32074. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q3TSG4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP
60 70 80 90 100
YPASGTTKRK YQEDSDPERS DYEEHQLQKE EEARKVKSGI RQIRLFSQDE
110 120 130 140 150
CSKIEARIDE VVSRAEKGLY NEHTVDRAPL RNKYFFGEGY TYGAQLQKRG
160 170 180 190 200
PGQERLYPPG DVDEIPDWVH QLVIQKLVEH RVIPEGFVNS AVINDYQPGG
210 220 230 240 250
CIVSHVDPIH IFERPIVSVS FFSDSALCFG CKFQFKPIRV SEPVLSLPVR
260 270 280 290 300
RGSVTVLSGY AADEITHCIR PQDIKERRAV IILRKTRLDA PRLETKSLSS
310 320 330 340 350
STLPPSYASD RLSGNTRDPA LKPKRSHRKA DPDAAHRPRI LEMDKEENRR
360 370 380 390
SVLLPTHRRR GSFSSENYWR KSYESSEDCP EAASSPTRKV KMRRH
Length:395
Mass (Da):44,411
Last modified:May 30, 2006 - v2
Checksum:i2822BF4BFFFEE7EF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67P → S in BAC35481 (PubMed:16141072).Curated1
Sequence conflicti85K → Q in BAC35481 (PubMed:16141072).Curated1
Sequence conflicti185E → K in AAH52076 (PubMed:15489334).Curated1
Sequence conflicti203V → L in BAC35481 (PubMed:16141072).Curated1
Sequence conflicti231 – 232CK → WQ in BAE36711 (PubMed:16141072).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK053695 mRNA. Translation: BAC35478.1.
AK053700 mRNA. Translation: BAC35481.1.
AK162072 mRNA. Translation: BAE36711.1.
AK163294 mRNA. Translation: BAE37281.1.
AL596386 Genomic DNA. Translation: CAI35332.1.
BC052076 mRNA. Translation: AAH52076.1.
CCDSiCCDS24794.1.
RefSeqiNP_766531.2. NM_172943.4.
UniGeneiMm.262056.

Genome annotation databases

EnsembliENSMUST00000044250; ENSMUSP00000049116; ENSMUSG00000042650.
GeneIDi268420.
KEGGimmu:268420.
UCSCiuc007jgd.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK053695 mRNA. Translation: BAC35478.1.
AK053700 mRNA. Translation: BAC35481.1.
AK162072 mRNA. Translation: BAE36711.1.
AK163294 mRNA. Translation: BAE37281.1.
AL596386 Genomic DNA. Translation: CAI35332.1.
BC052076 mRNA. Translation: AAH52076.1.
CCDSiCCDS24794.1.
RefSeqiNP_766531.2. NM_172943.4.
UniGeneiMm.262056.

3D structure databases

ProteinModelPortaliQ3TSG4.
SMRiQ3TSG4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000049116.

PTM databases

iPTMnetiQ3TSG4.
PhosphoSitePlusiQ3TSG4.

Proteomic databases

EPDiQ3TSG4.
MaxQBiQ3TSG4.
PaxDbiQ3TSG4.
PeptideAtlasiQ3TSG4.
PRIDEiQ3TSG4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000044250; ENSMUSP00000049116; ENSMUSG00000042650.
GeneIDi268420.
KEGGimmu:268420.
UCSCiuc007jgd.2. mouse.

Organism-specific databases

CTDi54890.
MGIiMGI:2144489. Alkbh5.

Phylogenomic databases

eggNOGiENOG410INB3. Eukaryota.
ENOG410Y0IS. LUCA.
GeneTreeiENSGT00390000009298.
HOGENOMiHOG000007505.
HOVERGENiHBG080833.
InParanoidiQ3TSG4.
KOiK10767.
OMAiWVHELVI.
OrthoDBiEOG091G0KLO.
PhylomeDBiQ3TSG4.
TreeFamiTF329212.

Enzyme and pathway databases

ReactomeiR-MMU-73943. Reversal of alkylation damage by DNA dioxygenases.

Miscellaneous databases

PROiQ3TSG4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000042650.
CleanExiMM_ALKBH5.
GenevisibleiQ3TSG4. MM.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiIPR027450. AlkB-like.
IPR032860. ALKBH5.
[Graphical view]
PANTHERiPTHR32074. PTHR32074. 1 hit.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALKB5_MOUSE
AccessioniPrimary (citable) accession number: Q3TSG4
Secondary accession number(s): Q80US0, Q8BKB9, Q8BKC1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: May 30, 2006
Last modified: November 30, 2016
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.