ALKB5_DANRE
ID ALKB5_DANRE Reviewed; 352 AA.
AC Q08BA6;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=RNA demethylase ALKBH5 {ECO:0000303|PubMed:24561204};
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 38-287 IN COMPLEX WITH
RP ALPHA-KETOGLUTARATE; MANGANESE AND SUCCINATE, FUNCTION, AND COFACTOR.
RX PubMed=24561204; DOI=10.1016/j.febslet.2014.02.021;
RA Chen W., Zhang L., Zheng G., Fu Y., Ji Q., Liu F., Chen H., He C.;
RT "Crystal structure of the RNA demethylase ALKBH5 from zebrafish.";
RL FEBS Lett. 588:892-898(2014).
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 (PubMed:24561204). Can also demethylate N(6)-methyladenosine
CC in single-stranded DNA (in vitro) (By similarity). Requires molecular
CC oxygen, alpha-ketoglutarate and iron (PubMed:24561204).
CC {ECO:0000250|UniProtKB:Q6P6C2, ECO:0000269|PubMed:24561204}.
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:0000269|PubMed:24561204};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:24561204};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24561204}.
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q6P6C2}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR EMBL; AL928835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC124804; AAI24805.1; -; mRNA.
DR RefSeq; NP_001070855.1; NM_001077387.1.
DR PDB; 4NPL; X-ray; 1.65 A; A/B=38-287.
DR PDB; 4NPM; X-ray; 1.80 A; A/B=38-287.
DR PDBsum; 4NPL; -.
DR PDBsum; 4NPM; -.
DR AlphaFoldDB; Q08BA6; -.
DR SMR; Q08BA6; -.
DR MINT; Q08BA6; -.
DR STRING; 7955.ENSDARP00000086116; -.
DR PaxDb; Q08BA6; -.
DR PRIDE; Q08BA6; -.
DR Ensembl; ENSDART00000091683; ENSDARP00000086116; ENSDARG00000063003.
DR GeneID; 570158; -.
DR KEGG; dre:570158; -.
DR CTD; 54890; -.
DR ZFIN; ZDB-GENE-061013-602; alkbh5.
DR eggNOG; KOG4176; Eukaryota.
DR GeneTree; ENSGT00390000009298; -.
DR HOGENOM; CLU_047472_1_0_1; -.
DR InParanoid; Q08BA6; -.
DR OMA; KSMMPYR; -.
DR OrthoDB; 722070at2759; -.
DR PhylomeDB; Q08BA6; -.
DR TreeFam; TF329212; -.
DR BRENDA; 1.14.11.53; 928.
DR Reactome; R-DRE-73943; Reversal of alkylation damage by DNA dioxygenases.
DR PRO; PR:Q08BA6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000063003; Expressed in testis and 25 other tissues.
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; IDA:ZFIN.
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 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..352
FT /note="RNA demethylase ALKBH5"
FT /id="PRO_0000421248"
FT REGION 18..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..342
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 161..163
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:24561204"
FT BINDING 172
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24561204"
FT BINDING 174
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24561204"
FT BINDING 234
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24561204"
FT BINDING 245
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:24561204"
FT HELIX 42..55
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:4NPL"
FT HELIX 65..83
FT /evidence="ECO:0007829|PDB:4NPL"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:4NPL"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:4NPL"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:4NPL"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:4NPL"
FT TURN 202..205
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:4NPL"
FT HELIX 226..230
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:4NPL"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:4NPL"
FT STRAND 245..251
FT /evidence="ECO:0007829|PDB:4NPL"
SQ SEQUENCE 352 AA; 40592 MW; F892D47C9CC084D0 CRC64;
MAGFTDLREK LKSMTPHRDK VFEYSNGEKR KYRESDDDES EYEERRDAEA RRVKSGIKQA
SIFTLEECAR IEAKIDEVVA KADKGLYREH TVDRAPLRNK YFFGEGYTYG AQLEKRGPGQ
ERLYSKGEVD DIPDWVHELV IDRLVTHGVI PEGFVNSAVI NDYQPGGCIV SHVDPIHIFE
RPIVSVSFFS DSALCFGCKF LFKPIRVSEP VLHLPVRRGS VTVLSGYAAD DITHCIRPQD
IKERRAVIIL RKTRADAPRL DSNSLSPSIV SPKRRHILKA KRSHRKADPD AAHRPRVLEM
DKELQRRSLS SRQRRHDDGS SENSWRRADD REPAARYTHD HAPTRRVKMR RH
