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-JUL-2024, entry version 89. 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 specifically demethylates N(6)- CC methyladenosine (m6A) RNA, the most prevalent internal modification of CC messenger RNA (mRNA) in higher eukaryotes. Demethylates RNA by CC oxidative demethylation, which requires molecular oxygen, alpha- CC ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA CC processing, translation and export. {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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49521; 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 -!- DOMAIN: The C-terminal disordered region undergoes liquid-liquid phase CC separation (LLPS) for the formation of paraspeckle membraneless CC compartment. {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 AGR; Xenbase:XB-GENE-987580; -. 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:0006397; P:mRNA processing; IEA:InterPro. DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; ISS:UniProtKB. DR GO; GO:0010793; P:regulation of mRNA export from nucleus; ISS:UniProtKB. DR GO; GO:0050684; P:regulation of mRNA processing; 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; Disulfide bond; 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 ACT_SITE 105 FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 159 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 161 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 170 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:Q6P6C2" FT BINDING 232 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" 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" FT DISULFID 196..233 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 //