ID ALKB5_XENTR Reviewed; 358 AA. AC Q66JG8; F6VI63; F6VRK9; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 1. DT 24-JAN-2024, entry version 86. DE RecName: Full=RNA demethylase ALKBH5; DE EC=1.14.11.53 {ECO:0000250|UniProtKB:Q6P6C2}; DE AltName: Full=Alkylated DNA repair protein alkB homolog 5; DE AltName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5; GN Name=alkbh5; OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana. OX NCBI_TaxID=8364; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=20431018; DOI=10.1126/science.1183670; RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J., RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L., RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R., RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J., RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H., RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K., RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A., RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T., RA Khokha M.K., Richardson P.M., Rokhsar D.S.; RT "The genome of the Western clawed frog Xenopus tropicalis."; RL Science 328:633-636(2010). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Embryo; RG NIH - Xenopus Gene Collection (XGC) project; RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Dioxygenase that demethylates RNA by oxidative demethylation: CC specifically demethylates N(6)-methyladenosine (m6A) RNA, the most CC prevalent internal modification of messenger RNA (mRNA) in higher CC eukaryotes. Can also demethylate N(6)-methyladenosine in single- CC stranded DNA (in vitro) (By similarity). Requires molecular oxygen, CC alpha-ketoglutarate and iron (By similarity). Demethylation of m6A mRNA CC affects mRNA processing and export (By similarity). CC {ECO:0000250|UniProtKB:Q3TSG4, ECO:0000250|UniProtKB:Q6P6C2}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + an N(6)-methyladenosine in mRNA + O2 = an CC adenosine in mRNA + CO2 + formaldehyde + succinate; CC Xref=Rhea:RHEA:49520, Rhea:RHEA-COMP:12414, Rhea:RHEA-COMP:12417, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74411, CC ChEBI:CHEBI:74449; EC=1.14.11.53; CC Evidence={ECO:0000250|UniProtKB:Q6P6C2}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000250|UniProtKB:Q6P6C2}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6P6C2}; CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q6P6C2}. CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q6P6C2}. CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AAMC01050884; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AAMC01050885; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC080920; AAH80920.1; -; mRNA. DR RefSeq; NP_001008038.1; NM_001008037.1. DR AlphaFoldDB; Q66JG8; -. DR SMR; Q66JG8; -. DR STRING; 8364.ENSXETP00000024527; -. DR PaxDb; 8364-ENSXETP00000059003; -. DR DNASU; 493400; -. DR Ensembl; ENSXETT00000012702; ENSXETP00000012702; ENSXETG00000005769. DR GeneID; 493400; -. DR KEGG; xtr:493400; -. DR CTD; 54890; -. DR Xenbase; XB-GENE-987580; alkbh5. DR eggNOG; KOG4176; Eukaryota. DR InParanoid; Q66JG8; -. DR OMA; ENYWRRD; -. DR OrthoDB; 179931at2759; -. DR TreeFam; TF329212; -. DR Reactome; R-XTR-73943; Reversal of alkylation damage by DNA dioxygenases. DR Proteomes; UP000008143; Chromosome 9. DR Bgee; ENSXETG00000005769; Expressed in skeletal muscle tissue and 17 other cell types or tissues. DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0042382; C:paraspeckles; ISS:UniProtKB. DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140693; F:molecular condensate scaffold activity; ISS:UniProtKB. DR GO; GO:1990931; F:mRNA N6-methyladenosine dioxygenase activity; ISS:UniProtKB. DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB. DR GO; GO:0006406; P:mRNA export from nucleus; ISS:UniProtKB. DR GO; GO:0006397; P:mRNA processing; ISS:UniProtKB. DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; ISS:UniProtKB. DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; ISS:UniProtKB. DR GO; GO:0006417; P:regulation of translation; ISS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR Gene3D; 2.60.120.590; Alpha-ketoglutarate-dependent dioxygenase AlkB-like; 1. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR032860; ALKBH5. DR PANTHER; PTHR32074; RNA DEMETHYLASE ALKBH5; 1. DR PANTHER; PTHR32074:SF2; RNA DEMETHYLASE ALKBH5; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. PE 2: Evidence at transcript level; KW Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; KW Reference proteome. FT CHAIN 1..358 FT /note="RNA demethylase ALKBH5" FT /id="PRO_0000239286" FT REGION 1..50 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 259..312 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 334..358 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 11..34 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 259..275 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 286..312 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 334..352 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 159..161 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 170 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 172 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 232 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 243 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" SQ SEQUENCE 358 AA; 41677 MW; 69E3D4E37CC629C5 CRC64; MSATYTDLRE KLQSLYRDSP KEVRKRKQPT SDTEEEEAAS EPEEEEEARK VRSGIRQVRL FSPDECARIE AKIDEVVSRA EKGLYREHTV DRAPLRNKYF FGEGYTYGAQ LQRRGPGQER LYPKGEVDEI PAWVNELVIR RLVEHRVIPE GFVNSAVIND YQPGGCIVSH VDPIHIFERP IVSVSFFSDS ALCFGCKFQF KPIRVSEPVF FLPVQRGSVT VLSGYAADEI THCIRPQDIK ERRAVVILRK TRTEAPRLEM KSLSSSYQPE RLQGSNRQHI LKPKRSHRKA DPDAAHRPRI LEMDKEENRR SVLLPKQRRR SHFSSENYWR RSHDYVDTYT ETGEDDGSPV RKVKMRRH //