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 02-OCT-2024, entry version 152. 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=5-(carboxymethyl)uridine(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}; 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; 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. DR AlphaFoldDB; Q80Y20; -. DR SMR; Q80Y20; -. DR STRING; 10090.ENSMUSP00000148653; -. DR PhosphoSitePlus; Q80Y20; -. DR PaxDb; 10090-ENSMUSP00000061511; -. DR PeptideAtlas; Q80Y20; -. DR ProteomicsDB; 282073; -. [Q80Y20-1] DR ProteomicsDB; 282074; -. [Q80Y20-2] DR ProteomicsDB; 282075; -. [Q80Y20-3] DR Pumba; Q80Y20; -. DR Antibodypedia; 18165; 182 antibodies from 25 providers. DR DNASU; 67667; -. DR Ensembl; ENSMUST00000053407.13; ENSMUSP00000061511.6; ENSMUSG00000025899.15. [Q80Y20-1] DR Ensembl; ENSMUST00000165105.2; ENSMUSP00000125996.2; ENSMUSG00000025899.15. [Q80Y20-1] DR Ensembl; ENSMUST00000211933.2; ENSMUSP00000148653.2; ENSMUSG00000025899.15. [Q80Y20-1] DR Ensembl; ENSMUST00000212294.2; ENSMUSP00000148380.2; ENSMUSG00000025899.15. [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 AGR; MGI:1914917; -. 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; 5473013at2759; -. DR PhylomeDB; Q80Y20; -. DR TreeFam; TF316056; -. DR BRENDA; 2.1.1.229; 3474. DR BioGRID-ORCS; 67667; 5 hits in 77 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 230 other cell types or tissues. DR ExpressionAtlas; Q80Y20; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IEA:InterPro. DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB. DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IEA:InterPro. DR GO; GO:0106335; F:tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity; IDA:MGI. DR GO; GO:0016300; F:tRNA (uridine) 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:DNA damage response; ISS:UniProtKB. DR GO; GO:0030488; P:tRNA methylation; IMP:UniProtKB. DR GO; GO:0002098; P:tRNA wobble uridine modification; IDA:UniProtKB. DR CDD; cd02440; AdoMet_MTases; 1. DR CDD; cd12431; RRM_ALKBH8; 1. DR Gene3D; 3.30.70.330; -; 1. DR Gene3D; 2.60.120.590; Alpha-ketoglutarate-dependent dioxygenase AlkB-like; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR015095; AlkB_hom8_N. DR InterPro; IPR051422; AlkB_tRNA_MeTrf/Diox. 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 PANTHER; PTHR13069:SF21; ALKYLATED DNA REPAIR PROTEIN ALKB HOMOLOG 8; 1. DR PANTHER; PTHR13069; UNCHARACTERIZED; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1. DR Pfam; PF09004; ALKBH8_N; 1. DR Pfam; PF08241; Methyltransf_11; 1. DR Pfam; PF00076; RRM_1; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 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 //