ALKB8_MOUSE
ID ALKB8_MOUSE Reviewed; 664 AA.
AC Q80Y20; Q3TUG4; Q8BV08; Q9CX44;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Alkylated DNA repair protein alkB homolog 8;
DE AltName: Full=Probable alpha-ketoglutarate-dependent dioxygenase ABH8;
DE AltName: Full=S-adenosyl-L-methionine-dependent tRNA methyltransferase ABH8;
DE AltName: Full=tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ABH8;
DE EC=2.1.1.229 {ECO:0000250|UniProtKB:Q96BT7};
GN Name=Alkbh8;
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] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Head, and Testis;
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 MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
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 [3]
RP FUNCTION, COFACTOR, LACK OF DEMETHYLASE ACTIVITY, DOMAIN, AND MUTAGENESIS
RP OF HIS-238 AND ASP-240.
RX PubMed=20583019; DOI=10.1002/anie.201001242;
RA Fu Y., Dai Q., Zhang W., Ren J., Pan T., He C.;
RT "The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-
RT methoxycarbonylmethyluridine at the wobble position of tRNA.";
RL Angew. Chem. Int. Ed. Engl. 49:8885-8888(2010).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
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 [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20123966; DOI=10.1128/mcb.01602-09;
RA Songe-Moller L., van den Born E., Leihne V., Vagbo C.B., Kristoffersen T.,
RA Krokan H.E., Kirpekar F., Falnes P.O., Klungland A.;
RT "Mammalian ALKBH8 possesses tRNA methyltransferase activity required for
RT the biogenesis of multiple wobble uridine modifications implicated in
RT translational decoding.";
RL Mol. Cell. Biol. 30:1814-1827(2010).
CC -!- FUNCTION: Catalyzes the methylation of 5-carboxymethyl uridine to 5-
CC methylcarboxymethyl uridine at the wobble position of the anticodon
CC loop in tRNA via its methyltransferase domain (PubMed:20123966).
CC Catalyzes the last step in the formation of 5-methylcarboxymethyl
CC uridine at the wobble position of the anticodon loop in target tRNA
CC (PubMed:20123966). Has a preference for tRNA(Arg) and tRNA(Glu), and
CC does not bind tRNA(Lys) (By similarity). Binds tRNA and catalyzes the
CC iron and alpha-ketoglutarate dependent hydroxylation of 5-
CC methylcarboxymethyl uridine at the wobble position of the anticodon
CC loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-
CC methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly)
CC (PubMed:20583019). Required for normal survival after DNA damage (By
CC similarity). May inhibit apoptosis and promote cell survival and
CC angiogenesis (By similarity). {ECO:0000250|UniProtKB:Q96BT7,
CC ECO:0000269|PubMed:20123966, ECO:0000269|PubMed:20583019}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carboxymethyluridine(34) in tRNA + S-adenosyl-L-methionine =
CC 5-(2-methoxy-2-oxoethyl)uridine(34) in tRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:43208, Rhea:RHEA-COMP:10407, Rhea:RHEA-
CC COMP:10408, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74851,
CC ChEBI:CHEBI:74882; EC=2.1.1.229;
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:20583019};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305};
CC -!- SUBUNIT: Interacts with TRMT112. {ECO:0000250|UniProtKB:Q96BT7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96BT7}. Nucleus
CC {ECO:0000250|UniProtKB:Q96BT7}. Note=Predominantly cytoplasmic.
CC {ECO:0000250|UniProtKB:Q96BT7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q80Y20-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80Y20-2; Sequence=VSP_033931;
CC Name=3;
CC IsoId=Q80Y20-3; Sequence=VSP_033929, VSP_033930;
CC -!- DOMAIN: The Fe2OG dioxygenase domain does not have demethylase activity
CC with methylated nucleotides. {ECO:0000269|PubMed:20583019}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype.
CC {ECO:0000269|PubMed:20123966}.
CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC38223.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK020197; BAB32026.1; -; mRNA.
DR EMBL; AK081459; BAC38223.1; ALT_FRAME; mRNA.
DR EMBL; AK160783; BAE36007.1; -; mRNA.
DR EMBL; BC050863; AAH50863.1; -; mRNA.
DR CCDS; CCDS22792.1; -. [Q80Y20-1]
DR RefSeq; NP_080579.1; NM_026303.1. [Q80Y20-1]
DR RefSeq; XP_006509943.1; XM_006509880.3. [Q80Y20-1]
DR AlphaFoldDB; Q80Y20; -.
DR SMR; Q80Y20; -.
DR STRING; 10090.ENSMUSP00000061511; -.
DR PhosphoSitePlus; Q80Y20; -.
DR EPD; Q80Y20; -.
DR MaxQB; Q80Y20; -.
DR PaxDb; Q80Y20; -.
DR PeptideAtlas; Q80Y20; -.
DR PRIDE; Q80Y20; -.
DR ProteomicsDB; 282073; -. [Q80Y20-1]
DR ProteomicsDB; 282074; -. [Q80Y20-2]
DR ProteomicsDB; 282075; -. [Q80Y20-3]
DR Antibodypedia; 18165; 161 antibodies from 25 providers.
DR DNASU; 67667; -.
DR Ensembl; ENSMUST00000053407; ENSMUSP00000061511; ENSMUSG00000025899. [Q80Y20-1]
DR Ensembl; ENSMUST00000165105; ENSMUSP00000125996; ENSMUSG00000025899. [Q80Y20-1]
DR Ensembl; ENSMUST00000211933; ENSMUSP00000148653; ENSMUSG00000025899. [Q80Y20-1]
DR Ensembl; ENSMUST00000212294; ENSMUSP00000148380; ENSMUSG00000025899. [Q80Y20-2]
DR GeneID; 67667; -.
DR KEGG; mmu:67667; -.
DR UCSC; uc009oat.1; mouse. [Q80Y20-1]
DR UCSC; uc009oau.1; mouse. [Q80Y20-3]
DR UCSC; uc012gnj.1; mouse. [Q80Y20-2]
DR CTD; 91801; -.
DR MGI; MGI:1914917; Alkbh8.
DR VEuPathDB; HostDB:ENSMUSG00000025899; -.
DR eggNOG; KOG1331; Eukaryota.
DR eggNOG; KOG4176; Eukaryota.
DR GeneTree; ENSGT00940000158563; -.
DR HOGENOM; CLU_029501_4_0_1; -.
DR InParanoid; Q80Y20; -.
DR OMA; PWKTKDE; -.
DR OrthoDB; 996085at2759; -.
DR PhylomeDB; Q80Y20; -.
DR TreeFam; TF316056; -.
DR BRENDA; 2.1.1.229; 3474.
DR BioGRID-ORCS; 67667; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Alkbh8; mouse.
DR PRO; PR:Q80Y20; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q80Y20; protein.
DR Bgee; ENSMUSG00000025899; Expressed in manus and 227 other tissues.
DR ExpressionAtlas; Q80Y20; baseline and differential.
DR Genevisible; Q80Y20; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0106335; F:tRNA (carboxymethyluridine(34)-5-O)-methyltransferase activity; IDA:MGI.
DR GO; GO:0016300; F:tRNA (uracil) methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0030488; P:tRNA methylation; IMP:UniProtKB.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IDA:UniProtKB.
DR CDD; cd12431; RRM_ALKBH8; 1.
DR Gene3D; 2.60.120.590; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR027450; AlkB-like.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR015095; AlkB_hom8_N.
DR InterPro; IPR034256; ALKBH8_RRM.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
DR Pfam; PF09004; DUF1891; 1.
DR Pfam; PF08241; Methyltransf_11; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Iron; Metal-binding; Methyltransferase;
KW Multifunctional enzyme; Nucleus; Reference proteome; RNA-binding;
KW S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..664
FT /note="Alkylated DNA repair protein alkB homolog 8"
FT /id="PRO_0000337127"
FT DOMAIN 45..120
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 220..337
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 411..664
FT /note="Methyltransferase domain"
FT /evidence="ECO:0000250"
FT BINDING 227..229
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 238
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000305|PubMed:20583019"
FT BINDING 240
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805,
FT ECO:0000305|PubMed:20583019"
FT BINDING 242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 292
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 328
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 334
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT BINDING 349
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96BT7"
FT VAR_SEQ 123..169
FT /note="AQWKNMGLEALPPGLLVVEEIISSEEEKKLLESVNWTEDTGNQNFQR -> G
FT TLTLASFNLLFLCEFSSYRESLSIILYVWEVCAGVLDHAVPVGVKG (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033929"
FT VAR_SEQ 170..664
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033930"
FT VAR_SEQ 199..233
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033931"
FT MUTAGEN 238
FT /note="H->A: Abolishes hydroxylation of 5-
FT methylcarboxymethyl uridine."
FT /evidence="ECO:0000269|PubMed:20583019"
FT MUTAGEN 240
FT /note="D->A: Abolishes hydroxylation of 5-
FT methylcarboxymethyl uridine."
FT /evidence="ECO:0000269|PubMed:20583019"
FT CONFLICT 88
FT /note="Q -> H (in Ref. 1; BAC38223)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="A -> T (in Ref. 1; BAC38223)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="K -> R (in Ref. 1; BAC38223)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 664 AA; 74768 MW; 624A9F48768A903E CRC64;
MNINHKGVLK LTKMEKKFLR KQSKARHVLL KHEGIQAVSY PTQSLVIANG GLGNGVSRKQ
LLLTLEKCGP VEALLMPPNK PYAFVIFQTI EESKKAYFTL NGKEIIDDLG QKIFLYLNFV
EKAQWKNMGL EALPPGLLVV EEIISSEEEK KLLESVNWTE DTGNQNFQRS LKHRRVKHFG
YEFHYESNTV DKDKPLPGGL PEVCSSILEK LLKEGYIKHK PDQLTINQYE PGHGIPAHID
THSAFEDEII SLSLGSAIVM DFKHPEGVTV QVMLPRRSLL VMTGESRYLW THGITPRKFD
TVQASEQFKG GIITSDIGDL TLSKRGMRTS FTFRKVRRMP CNCSYSSVCD RQRKATPPSL
TESSKEALEL EQKHVHQVYN EIASHFSSTR HSPWPRIVEF LKALPSGSIV ADIGCGNGKY
LGINKDLYMI GCDRSQNLVD ICRERQFQAL VCDALAVPVR SGSCDACISI AVIHHFATAE
RRVEALQELA RLLRPGGQAL IYVWAMEQEY KNQKSKYLRG KRISQGDKDE LNSATSTEEF
LVNQTPEGVN EDPALSVNSS SITKEEEYKS RKVPNSELPI HINRTCFHSQ DVLVPWHLKR
NPGKDKAIEP SGVAGCPDPS PVFHRYYHVF CDGELEASCQ AVGDVSILQS YYDQGNWCVV
LQKV
