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 25-MAY-2022, entry version 78. 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.ENSXETP00000059003; -. DR PRIDE; Q66JG8; -. 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 GeneTree; ENSGT00390000009298; -. DR InParanoid; Q66JG8; -. DR OrthoDB; 722070at2759; -. DR TreeFam; TF329212; -. DR Reactome; R-XTR-73943; Reversal of alkylation damage by DNA dioxygenases. DR Proteomes; UP000008143; Chromosome 9. DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; 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:1990931; F:mRNA N6-methyladenosine dioxygenase activity; ISS:UniProtKB. DR GO; GO:0035515; F:oxidative RNA demethylase activity; IBA:GO_Central. DR GO; GO:0006406; P:mRNA export from nucleus; ISS:UniProtKB. DR GO; GO:0006397; P:mRNA processing; ISS:UniProtKB. DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; 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; -; 1. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR032860; ALKBH5. DR PANTHER; PTHR32074; PTHR32074; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 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 159..161 FT /note="Alpha-ketoglutarate binding" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" 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 METAL 170 FT /note="Iron; catalytic" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT METAL 172 FT /note="Iron; catalytic" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT METAL 232 FT /note="Iron; catalytic" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 243 FT /note="Alpha-ketoglutarate" 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 //