ALKB5_MOUSE
ID ALKB5_MOUSE Reviewed; 395 AA.
AC Q3TSG4; Q80US0; Q8BKB9; Q8BKC1;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=RNA demethylase ALKBH5 {ECO:0000305};
DE EC=1.14.11.53 {ECO:0000305|PubMed:29279410};
DE AltName: Full=Alkylated DNA repair protein alkB homolog 5;
DE AltName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5;
GN Name=Alkbh5 {ECO:0000303|PubMed:23177736, ECO:0000312|MGI:MGI:2144489};
GN Synonyms=Abh5, Ofoxd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg, and Eye;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362; SER-372 AND SER-385, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-362 AND SER-385, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23177736; DOI=10.1016/j.molcel.2012.10.015;
RA Zheng G., Dahl J.A., Niu Y., Fedorcsak P., Huang C.M., Li C.J., Vagbo C.B.,
RA Shi Y., Wang W.L., Song S.H., Lu Z., Bosmans R.P., Dai Q., Hao Y.J.,
RA Yang X., Zhao W.M., Tong W.M., Wang X.J., Bogdan F., Furu K., Fu Y.,
RA Jia G., Zhao X., Liu J., Krokan H.E., Klungland A., Yang Y.G., He C.;
RT "ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and
RT mouse fertility.";
RL Mol. Cell 49:18-29(2013).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=29279410; DOI=10.1073/pnas.1717794115;
RA Tang C., Klukovich R., Peng H., Wang Z., Yu T., Zhang Y., Zheng H.,
RA Klungland A., Yan W.;
RT "ALKBH5-dependent m6A demethylation controls splicing and stability of long
RT 3'-UTR mRNAs in male germ cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E325-E333(2018).
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:29279410). Can also demethylate N(6)-methyladenosine
CC in single-stranded DNA (in vitro) (By similarity). Requires molecular
CC oxygen, alpha-ketoglutarate and iron (By similarity). Demethylation of
CC m6A mRNA affects mRNA processing and export (By similarity). Required
CC for the late meiotic and haploid phases of spermatogenesis by mediating
CC m6A demethylation in spermatocytes and round spermatids: m6A
CC demethylation of target transcripts is required for correct splicing
CC and the production of longer 3'-UTR mRNAs in male germ cells
CC (PubMed:23177736, PubMed:29279410). {ECO:0000250|UniProtKB:Q6P6C2,
CC ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:29279410}.
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:0000305|PubMed:29279410};
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:0000269|PubMed:29279410}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in testis
CC (PubMed:23177736). In testis, present in almost all testicular cell
CC types except elongating and elongated spermatids (at protein level)
CC (PubMed:29279410). Among spermatogenic cells, present at high level in
CC spermatocytes; medium levels in spermatogonia and lower levels in round
CC spermatids (at protein level) (PubMed:29279410).
CC {ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:29279410}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable, anatomically normal and reach
CC adulthood but display impaired fertility resulting from apoptosis that
CC affects meiotic metaphase-stage spermatocytes (PubMed:23177736,
CC PubMed:29279410). Testes are significantly smaller and histological
CC analysis of testis sections reveal aberrant tubular architecture and
CC size (PubMed:23177736, PubMed:29279410). The number of spermatozoa
CC released from cauda epididymes is dramatically reduced, and the
CC spermatozoa are morphologically abnormal with greatly compromised
CC motility (PubMed:23177736). Male mice display increased m6A in mRNAs in
CC spermatocytes, leading to aberrant splicing and production of shorter
CC transcripts that are rapidly degraded (PubMed:29279410).
CC {ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:29279410}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
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DR EMBL; AK053695; BAC35478.1; -; mRNA.
DR EMBL; AK053700; BAC35481.1; -; mRNA.
DR EMBL; AK162072; BAE36711.1; -; mRNA.
DR EMBL; AK163294; BAE37281.1; -; mRNA.
DR EMBL; AL596386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC052076; AAH52076.1; -; mRNA.
DR CCDS; CCDS24794.1; -.
DR RefSeq; NP_766531.2; NM_172943.4.
DR AlphaFoldDB; Q3TSG4; -.
DR SMR; Q3TSG4; -.
DR BioGRID; 234497; 1.
DR IntAct; Q3TSG4; 1.
DR MINT; Q3TSG4; -.
DR STRING; 10090.ENSMUSP00000049116; -.
DR iPTMnet; Q3TSG4; -.
DR PhosphoSitePlus; Q3TSG4; -.
DR EPD; Q3TSG4; -.
DR jPOST; Q3TSG4; -.
DR MaxQB; Q3TSG4; -.
DR PaxDb; Q3TSG4; -.
DR PeptideAtlas; Q3TSG4; -.
DR PRIDE; Q3TSG4; -.
DR ProteomicsDB; 296397; -.
DR Antibodypedia; 2003; 144 antibodies from 25 providers.
DR DNASU; 268420; -.
DR Ensembl; ENSMUST00000044250; ENSMUSP00000049116; ENSMUSG00000042650.
DR GeneID; 268420; -.
DR KEGG; mmu:268420; -.
DR UCSC; uc007jgd.2; mouse.
DR CTD; 54890; -.
DR MGI; MGI:2144489; Alkbh5.
DR VEuPathDB; HostDB:ENSMUSG00000042650; -.
DR eggNOG; KOG4176; Eukaryota.
DR GeneTree; ENSGT00390000009298; -.
DR HOGENOM; CLU_047472_1_0_1; -.
DR InParanoid; Q3TSG4; -.
DR OMA; KSMMPYR; -.
DR OrthoDB; 722070at2759; -.
DR PhylomeDB; Q3TSG4; -.
DR TreeFam; TF329212; -.
DR BRENDA; 1.14.11.53; 3474.
DR Reactome; R-MMU-73943; Reversal of alkylation damage by DNA dioxygenases.
DR BioGRID-ORCS; 268420; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Alkbh5; mouse.
DR PRO; PR:Q3TSG4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3TSG4; protein.
DR Bgee; ENSMUSG00000042650; Expressed in pigmented layer of retina and 250 other tissues.
DR Genevisible; Q3TSG4; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; IMP:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IMP: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; IMP:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP: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_0000239284"
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:21183079"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
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:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CROSSLNK 329
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q6P6C2"
FT CONFLICT 67
FT /note="P -> S (in Ref. 1; BAC35481)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="K -> Q (in Ref. 1; BAC35481)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="E -> K (in Ref. 3; AAH52076)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="V -> L (in Ref. 1; BAC35481)"
FT /evidence="ECO:0000305"
FT CONFLICT 231..232
FT /note="CK -> WQ (in Ref. 1; BAE36711)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 395 AA; 44411 MW; 2822BF4BFFFEE7EF CRC64;
MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP YPASGTTKRK
YQEDSDPERS DYEEHQLQKE EEARKVKSGI RQIRLFSQDE CSKIEARIDE VVSRAEKGLY
NEHTVDRAPL RNKYFFGEGY TYGAQLQKRG PGQERLYPPG DVDEIPDWVH QLVIQKLVEH
RVIPEGFVNS AVINDYQPGG CIVSHVDPIH IFERPIVSVS FFSDSALCFG CKFQFKPIRV
SEPVLSLPVR RGSVTVLSGY AADEITHCIR PQDIKERRAV IILRKTRLDA PRLETKSLSS
STLPPSYASD RLSGNTRDPA LKPKRSHRKA DPDAAHRPRI LEMDKEENRR SVLLPTHRRR
GSFSSENYWR KSYESSEDCP EAASSPTRKV KMRRH
