UniProtKB - Q3TSG4 (ALKB5_MOUSE)
Protein
RNA demethylase ALKBH5
Gene
Alkbh5
Organism
Mus musculus (Mouse)
Status
Functioni
Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N6-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:29279410). Can also demethylate N6-methyladenosine in single-stranded DNA (in vitro) (By similarity). Requires molecular oxygen, alpha-ketoglutarate and iron (By similarity). Demethylation of m6A mRNA affects mRNA processing and export (By similarity). Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (PubMed:23177736, PubMed:29279410).By similarity2 Publications
Catalytic activityi
- 2-oxoglutarate + N6-methyladenosine in mRNA + O2 = adenosine in mRNA + CO2 + formaldehyde + succinate1 Publication
Cofactori
Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 205 | Iron; catalyticBy similarity | 1 | |
Metal bindingi | 207 | Iron; catalyticBy similarity | 1 | |
Metal bindingi | 267 | Iron; catalyticBy similarity | 1 | |
Binding sitei | 278 | Alpha-ketoglutarateBy similarity | 1 |
GO - Molecular functioni
- 2-oxoglutarate-dependent dioxygenase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- oxidative RNA demethylase activity Source: GO_Central
- RNA N6-methyladenosine dioxygenase activity Source: UniProtKB
GO - Biological processi
- cell differentiation Source: UniProtKB-KW
- mRNA export from nucleus Source: UniProtKB
- mRNA processing Source: UniProtKB
- oxidative single-stranded RNA demethylation Source: UniProtKB
- regulation of mRNA stability Source: UniProtKB
- response to hypoxia Source: UniProtKB
- spermatogenesis Source: UniProtKB
Keywordsi
Molecular function | Dioxygenase, Oxidoreductase |
Biological process | Differentiation, Spermatogenesis |
Ligand | Iron, Metal-binding |
Enzyme and pathway databases
Reactomei | R-MMU-73943, Reversal of alkylation damage by DNA dioxygenases |
Names & Taxonomyi
Protein namesi | Recommended name: RNA demethylase ALKBH5Curated (EC:1.14.11.-1 Publication)Alternative name(s): Alkylated DNA repair protein alkB homolog 5 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2144489, Alkbh5 |
Subcellular locationi
Nucleus
- Nucleus speckle 1 Publication
Cytosol
- cytosol Source: MGI
Golgi apparatus
- Golgi apparatus Source: MGI
Nucleus
- nuclear speck Source: UniProtKB
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
Mice are viable, anatomically normal and reach adulthood but display impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes (PubMed:23177736, PubMed:29279410). Testes are significantly smaller and histological analysis of testis sections reveal aberrant tubular architecture and size (PubMed:23177736, PubMed:29279410). The number of spermatozoa released from cauda epididymes is dramatically reduced, and the spermatozoa are morphologically abnormal with greatly compromised motility (PubMed:23177736). Male mice display increased m6A in mRNAs in spermatocytes, leading to aberrant splicing and production of shorter transcripts that are rapidly degraded (PubMed:29279410).2 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000239284 | 2 – 395 | RNA demethylase ALKBH5Add BLAST | 394 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 65 | PhosphoserineCombined sources | 1 | |
Modified residuei | 70 | PhosphoserineBy similarity | 1 | |
Modified residuei | 72 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 133 | N6-acetyllysineBy similarity | 1 | |
Cross-linki | 329 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 360 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 362 | PhosphoserineCombined sources | 1 | |
Modified residuei | 372 | PhosphoserineCombined sources | 1 | |
Modified residuei | 375 | PhosphoserineBy similarity | 1 | |
Modified residuei | 385 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q3TSG4 |
jPOSTi | Q3TSG4 |
MaxQBi | Q3TSG4 |
PaxDbi | Q3TSG4 |
PeptideAtlasi | Q3TSG4 |
PRIDEi | Q3TSG4 |
PTM databases
iPTMneti | Q3TSG4 |
PhosphoSitePlusi | Q3TSG4 |
Expressioni
Tissue specificityi
Widely expressed, with highest expression in testis (PubMed:23177736). In testis, present in almost all testicular cell types except elongating and elongated spermatids (at protein level) (PubMed:29279410). Among spermatogenic cells, present at high level in spermatocytes; medium levels in spermatogonia and lower levels in round spermatids (at protein level) (PubMed:29279410).2 Publications
Gene expression databases
Bgeei | ENSMUSG00000042650, Expressed in cumulus cell and 298 other tissues |
Genevisiblei | Q3TSG4, MM |
Interactioni
Subunit structurei
Monomer.
By similarityProtein-protein interaction databases
BioGRIDi | 234497, 1 interactor |
STRINGi | 10090.ENSMUSP00000049116 |
Miscellaneous databases
RNActi | Q3TSG4, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 194 – 196 | Alpha-ketoglutarate bindingBy similarity | 3 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 68 – 117 | Sequence analysisAdd BLAST | 50 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 30 – 48 | Ala-richAdd BLAST | 19 |
Sequence similaritiesi
Belongs to the alkB family.Curated
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG4176, Eukaryota |
GeneTreei | ENSGT00390000009298 |
HOGENOMi | CLU_047472_1_0_1 |
InParanoidi | Q3TSG4 |
OMAi | ENYWRRD |
OrthoDBi | 722070at2759 |
PhylomeDBi | Q3TSG4 |
TreeFami | TF329212 |
Family and domain databases
Gene3Di | 2.60.120.590, 1 hit |
InterProi | View protein in InterPro IPR027450, AlkB-like IPR037151, AlkB-like_sf IPR032860, ALKBH5 |
PANTHERi | PTHR32074, PTHR32074, 2 hits |
Pfami | View protein in Pfam PF13532, 2OG-FeII_Oxy_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q3TSG4-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 67 | P → S in BAC35481 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 85 | K → Q in BAC35481 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 185 | E → K in AAH52076 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 203 | V → L in BAC35481 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 231 – 232 | CK → WQ in BAE36711 (PubMed:16141072).Curated | 2 |
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 No translation available. BC052076 mRNA Translation: AAH52076.1 |
CCDSi | CCDS24794.1 |
RefSeqi | NP_766531.2, NM_172943.4 |
Genome annotation databases
Ensembli | ENSMUST00000044250; ENSMUSP00000049116; ENSMUSG00000042650 |
GeneIDi | 268420 |
KEGGi | mmu:268420 |
UCSCi | uc007jgd.2, mouse |
Similar proteinsi
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 No translation available. BC052076 mRNA Translation: AAH52076.1 |
CCDSi | CCDS24794.1 |
RefSeqi | NP_766531.2, NM_172943.4 |
3D structure databases
SMRi | Q3TSG4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 234497, 1 interactor |
STRINGi | 10090.ENSMUSP00000049116 |
PTM databases
iPTMneti | Q3TSG4 |
PhosphoSitePlusi | Q3TSG4 |
Proteomic databases
EPDi | Q3TSG4 |
jPOSTi | Q3TSG4 |
MaxQBi | Q3TSG4 |
PaxDbi | Q3TSG4 |
PeptideAtlasi | Q3TSG4 |
PRIDEi | Q3TSG4 |
Protocols and materials databases
Antibodypediai | 2003, 124 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000044250; ENSMUSP00000049116; ENSMUSG00000042650 |
GeneIDi | 268420 |
KEGGi | mmu:268420 |
UCSCi | uc007jgd.2, mouse |
Organism-specific databases
CTDi | 54890 |
MGIi | MGI:2144489, Alkbh5 |
Phylogenomic databases
eggNOGi | KOG4176, Eukaryota |
GeneTreei | ENSGT00390000009298 |
HOGENOMi | CLU_047472_1_0_1 |
InParanoidi | Q3TSG4 |
OMAi | ENYWRRD |
OrthoDBi | 722070at2759 |
PhylomeDBi | Q3TSG4 |
TreeFami | TF329212 |
Enzyme and pathway databases
Reactomei | R-MMU-73943, Reversal of alkylation damage by DNA dioxygenases |
Miscellaneous databases
BioGRID-ORCSi | 268420, 1 hit in 17 CRISPR screens |
ChiTaRSi | Alkbh5, mouse |
PROi | PR:Q3TSG4 |
RNActi | Q3TSG4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000042650, Expressed in cumulus cell and 298 other tissues |
Genevisiblei | Q3TSG4, MM |
Family and domain databases
Gene3Di | 2.60.120.590, 1 hit |
InterProi | View protein in InterPro IPR027450, AlkB-like IPR037151, AlkB-like_sf IPR032860, ALKBH5 |
PANTHERi | PTHR32074, PTHR32074, 2 hits |
Pfami | View protein in Pfam PF13532, 2OG-FeII_Oxy_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ALKB5_MOUSE | |
Accessioni | Q3TSG4Primary (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: | December 2, 2020 | |
This is version 114 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families