ALKB5_RAT
ID ALKB5_RAT Reviewed; 395 AA.
AC D3ZKD3;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 77.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-70 AND SER-362, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). Can also demethylate N(6)-methyladenosine
CC in single-stranded DNA (in vitro). Requires molecular oxygen, alpha-
CC ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA
CC processing and export (By similarity). Required for the late meiotic
CC and haploid phases of spermatogenesis by mediating m6A demethylation in
CC spermatocytes and round spermatids: m6A demethylation of target
CC transcripts is required for correct splicing and the production of
CC longer 3'-UTR mRNAs in male germ cells (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:Q3TSG4}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR RefSeq; NP_001178572.1; NM_001191643.1.
DR AlphaFoldDB; D3ZKD3; -.
DR SMR; D3ZKD3; -.
DR STRING; 10116.ENSRNOP00000034155; -.
DR iPTMnet; D3ZKD3; -.
DR PhosphoSitePlus; D3ZKD3; -.
DR jPOST; D3ZKD3; -.
DR PaxDb; D3ZKD3; -.
DR PeptideAtlas; D3ZKD3; -.
DR PRIDE; D3ZKD3; -.
DR Ensembl; ENSRNOT00000034006; ENSRNOP00000034155; ENSRNOG00000028341.
DR GeneID; 303193; -.
DR KEGG; rno:303193; -.
DR UCSC; RGD:1309496; rat.
DR CTD; 54890; -.
DR RGD; 1309496; Alkbh5.
DR eggNOG; KOG4176; Eukaryota.
DR GeneTree; ENSGT00390000009298; -.
DR HOGENOM; CLU_047472_1_0_1; -.
DR InParanoid; D3ZKD3; -.
DR OMA; KSMMPYR; -.
DR OrthoDB; 722070at2759; -.
DR PhylomeDB; D3ZKD3; -.
DR TreeFam; TF329212; -.
DR Reactome; R-RNO-73943; Reversal of alkylation damage by DNA dioxygenases.
DR PRO; PR:D3ZKD3; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000028341; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; D3ZKD3; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
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:0043488; P:regulation of mRNA stability; 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; 2.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Differentiation; Dioxygenase; Iron;
KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Spermatogenesis; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT CHAIN 2..395
FT /note="RNA demethylase ALKBH5"
FT /id="PRO_0000421247"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..395
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 68..117
FT /evidence="ECO:0000255"
FT COMPBIAS 59..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 194..196
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT BINDING 205
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT BINDING 207
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT BINDING 267
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT BINDING 278
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 72
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 133
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 360
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TSG4"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TSG4"
FT CROSSLNK 329
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
SQ SEQUENCE 395 AA; 44453 MW; 94EE89A105EA89E2 CRC64;
MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP YPVSGTTKRK
YQEDSDPERS DYEEHQLQKE EEARKVKSGI RQIRLFSQDE CSKIEARIDE VVSRAEKGLY
NEHTVDRAPL RNKYFFGEGY TYGAQLQKRG PGQERLYPPG DVDEIPEWVH QLVIQKLVEH
RVIPEGFVNS AVINDYQPGG CIVSHVDPIH IFERPIVSVS FFSDSALCFG CKFQFKPIRV
SEPVLSLPVR RGSVTVLSGY AADEITHCIR PQDIKERRAV IILRKTRLDA PRLETKSLSS
STLPPSYASD RLSGNTRDPA LKPKRSHRKA DPDAAHRPRI LEMDKEENRR SVLLPTHRRR
GSFSSENYWR KSYESSEDCP EAASSPTRKV KMRRH
