ID ALKB8_HUMAN Reviewed; 664 AA. AC Q96BT7; B1Q2M0; B4DEF6; Q8N989; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 20-MAY-2008, sequence version 2. DT 24-JAN-2024, entry version 180. 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:0000269|PubMed:20123966, ECO:0000269|PubMed:20308323, ECO:0000269|PubMed:31079898}; GN Name=ALKBH8; Synonyms=ABH8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=17979886; DOI=10.1111/j.1582-4934.2007.00094.x; RA Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., RA Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H.; RT "Expression and sub-cellular localization of human ABH family molecules."; RL J. Cell. Mol. Med. 11:1105-1116(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). RC TISSUE=Brain, and Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Uterus; 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 [6] RP FUNCTION. RX PubMed=19293182; DOI=10.1158/0008-5472.can-08-3530; RA Shimada K., Nakamura M., Anai S., De Velasco M., Tanaka M., Tsujikawa K., RA Ouji Y., Konishi N.; RT "A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer RT progression."; RL Cancer Res. 69:3157-3164(2009). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TRMT112. 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). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH RP TRMT112, INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=20308323; DOI=10.1128/mcb.01604-09; RA Fu D., Brophy J.A., Chan C.T., Atmore K.A., Begley U., Paules R.S., RA Dedon P.C., Begley T.J., Samson L.D.; RT "Human AlkB homolog ABH8 is a tRNA methyltransferase required for wobble RT uridine modification and DNA damage survival."; RL Mol. Cell. Biol. 30:2449-2459(2010). RN [9] RP FUNCTION, COFACTOR, AND INTERACTION WITH TRMT112. RX PubMed=21285950; DOI=10.1038/ncomms1173; RA van den Born E., Vagbo C.B., Songe-Moller L., Leihne V., Lien G.F., RA Leszczynska G., Malkiewicz A., Krokan H.E., Kirpekar F., Klungland A., RA Falnes P.O.; RT "ALKBH8-mediated formation of a novel diastereomeric pair of wobble RT nucleosides in mammalian tRNA."; RL Nat. Commun. 2:172-172(2011). RN [10] RP INTERACTION WITH TRMT112, AND SUBCELLULAR LOCATION. RX PubMed=34948388; DOI=10.3390/ijms222413593; RA Brumele B., Mutso M., Telanne L., Ounap K., Spunde K., Abroi A., Kurg R.; RT "Human TRMT112-Methyltransferase Network Consists of Seven Partners RT Interacting with a Common Co-Factor."; RL Int. J. Mol. Sci. 22:13593-13593(2021). RN [11] RP STRUCTURE BY NMR OF 25-125. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of RNA binding domain in hypothetical protein RT LOC91801."; RL Submitted (NOV-2005) to the PDB data bank. RN [12] RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 25-355 IN COMPLEX WITH RP ALPHA-KETOGLUTARATE; MANGANESE AND ZINC, COFACTOR, INTERACTION WITH RP TRMT112, AND RNA-BINDING. RX PubMed=22065580; DOI=10.1074/jbc.m111.286187; RA Pastore C., Topalidou I., Forouhar F., Yan A.C., Levy M., Hunt J.F.; RT "Crystal structure and RNA binding properties of the RNA recognition motif RT (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing RT tRNA hypermodification."; RL J. Biol. Chem. 287:2130-2143(2012). RN [13] RP INVOLVEMENT IN MRT71, VARIANT MRT71 554-ALA--ALA-664 DEL, CHARACTERIZATION RP OF VARIANT MRT71 554-ALA--ALA-664 DEL, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=31079898; DOI=10.1016/j.ajhg.2019.03.026; RA Monies D., Vaagboe C.B., Al-Owain M., Alhomaidi S., Alkuraya F.S.; RT "Recessive truncating mutations in ALKBH8 cause intellectual disability and RT severe impairment of wobble uridine modification."; RL Am. J. Hum. Genet. 104:1202-1209(2019). 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 PubMed:20308323, PubMed:31079898). Catalyzes the last step in the CC formation of 5-methylcarboxymethyl uridine at the wobble position of CC the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). CC Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind CC tRNA(Lys)(PubMed:20308323). Binds tRNA and catalyzes the iron and CC alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl CC uridine at the wobble position of the anticodon loop in tRNA via its CC dioxygenase domain, giving rise to 5-(S)- CC methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) CC (PubMed:21285950). Required for normal survival after DNA damage CC (PubMed:20308323). May inhibit apoptosis and promote cell survival and CC angiogenesis (PubMed:19293182). {ECO:0000269|PubMed:19293182, CC ECO:0000269|PubMed:20123966, ECO:0000269|PubMed:20308323, CC ECO:0000269|PubMed:21285950, ECO:0000269|PubMed:31079898}. 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 Evidence={ECO:0000269|PubMed:20123966, ECO:0000269|PubMed:20308323, CC ECO:0000269|PubMed:31079898}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:21285950, ECO:0000305|PubMed:22065580}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305}; CC -!- SUBUNIT: Interacts with TRMT112. {ECO:0000269|PubMed:20123966, CC ECO:0000269|PubMed:20308323, ECO:0000269|PubMed:21285950, CC ECO:0000269|PubMed:22065580, ECO:0000269|PubMed:34948388}. CC -!- INTERACTION: CC Q96BT7; Q9UI30: TRMT112; NbExp=10; IntAct=EBI-10825637, EBI-373326; CC Q96BT7-2; Q86V38: ATN1; NbExp=3; IntAct=EBI-13329511, EBI-11954292; CC Q96BT7-2; Q92876: KLK6; NbExp=3; IntAct=EBI-13329511, EBI-2432309; CC Q96BT7-2; P55081: MFAP1; NbExp=3; IntAct=EBI-13329511, EBI-1048159; CC Q96BT7-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-13329511, EBI-79165; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17979886, CC ECO:0000269|PubMed:20308323, ECO:0000269|PubMed:34948388}. Nucleus CC {ECO:0000269|PubMed:20308323}. Note=Predominantly cytoplasmic. CC {ECO:0000269|PubMed:20308323}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q96BT7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96BT7-2; Sequence=VSP_033927, VSP_033928; CC Name=3; CC IsoId=Q96BT7-3; Sequence=VSP_033925, VSP_033926; CC Name=4; CC IsoId=Q96BT7-4; Sequence=VSP_039159; CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in CC spleen, followed by pancreas and lung. {ECO:0000269|PubMed:17979886}. CC -!- INDUCTION: Up-regulated after DNA damage. Induction is mediated via CC ATM. {ECO:0000269|PubMed:20308323}. CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 71 CC (MRT71) [MIM:618504]: A form of intellectual disability, a disorder CC characterized by significantly below average general intellectual CC functioning associated with impairments in adaptive behavior and CC manifested during the developmental period. MRT71 features include CC impaired intellectual development, global developmental delay, mildly CC delayed walking, poor language, seizures in the first years of life, CC and behavioral abnormalities. {ECO:0000269|PubMed:31079898}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: May be due to competing donor splice site. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the alkB family. {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; AB218768; BAG16270.1; -; mRNA. DR EMBL; AK095523; BAC04566.1; -; mRNA. DR EMBL; AK293603; BAG57067.1; -; mRNA. DR EMBL; AK304413; BAG65244.1; -; mRNA. DR EMBL; AP001823; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW67089.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67090.1; -; Genomic_DNA. DR EMBL; BC015183; AAH15183.1; -; mRNA. DR CCDS; CCDS8337.2; -. [Q96BT7-1] DR RefSeq; NP_001287939.1; NM_001301010.1. [Q96BT7-1] DR RefSeq; NP_620130.2; NM_138775.2. [Q96BT7-1] DR PDB; 2CQ2; NMR; -; A=25-125. DR PDB; 3THP; X-ray; 3.20 A; A=25-355. DR PDB; 3THT; X-ray; 3.01 A; A/B/C/D=25-355. DR PDBsum; 2CQ2; -. DR PDBsum; 3THP; -. DR PDBsum; 3THT; -. DR AlphaFoldDB; Q96BT7; -. DR SMR; Q96BT7; -. DR BioGRID; 124880; 8. DR ComplexPortal; CPX-2861; ALKBH8-TRM112 methyltransferase complex. DR IntAct; Q96BT7; 16. DR STRING; 9606.ENSP00000397673; -. DR GlyGen; Q96BT7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96BT7; -. DR PhosphoSitePlus; Q96BT7; -. DR BioMuta; ALKBH8; -. DR DMDM; 189027650; -. DR EPD; Q96BT7; -. DR jPOST; Q96BT7; -. DR MassIVE; Q96BT7; -. DR MaxQB; Q96BT7; -. DR PaxDb; 9606-ENSP00000397673; -. DR PeptideAtlas; Q96BT7; -. DR ProteomicsDB; 76112; -. [Q96BT7-1] DR ProteomicsDB; 76113; -. [Q96BT7-2] DR ProteomicsDB; 76114; -. [Q96BT7-3] DR ProteomicsDB; 76115; -. [Q96BT7-4] DR Pumba; Q96BT7; -. DR Antibodypedia; 18165; 196 antibodies from 25 providers. DR DNASU; 91801; -. DR Ensembl; ENST00000260318.6; ENSP00000260318.2; ENSG00000137760.15. [Q96BT7-2] DR Ensembl; ENST00000389568.7; ENSP00000374219.3; ENSG00000137760.15. [Q96BT7-1] DR Ensembl; ENST00000417449.6; ENSP00000397673.3; ENSG00000137760.15. [Q96BT7-1] DR Ensembl; ENST00000428149.7; ENSP00000415885.2; ENSG00000137760.15. [Q96BT7-1] DR Ensembl; ENST00000429370.5; ENSP00000391225.1; ENSG00000137760.15. [Q96BT7-3] DR GeneID; 91801; -. DR KEGG; hsa:91801; -. DR MANE-Select; ENST00000428149.7; ENSP00000415885.2; NM_138775.3; NP_620130.2. DR UCSC; uc009yxp.4; human. [Q96BT7-1] DR AGR; HGNC:25189; -. DR CTD; 91801; -. DR DisGeNET; 91801; -. DR GeneCards; ALKBH8; -. DR HGNC; HGNC:25189; ALKBH8. DR HPA; ENSG00000137760; Low tissue specificity. DR MalaCards; ALKBH8; -. DR MIM; 613306; gene. DR MIM; 618504; phenotype. DR neXtProt; NX_Q96BT7; -. DR OpenTargets; ENSG00000137760; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR PharmGKB; PA143485296; -. DR VEuPathDB; HostDB:ENSG00000137760; -. DR eggNOG; KOG1331; Eukaryota. DR eggNOG; KOG4176; Eukaryota. DR GeneTree; ENSGT00940000158563; -. DR HOGENOM; CLU_1173010_0_0_1; -. DR InParanoid; Q96BT7; -. DR OrthoDB; 5473013at2759; -. DR PhylomeDB; Q96BT7; -. DR TreeFam; TF316056; -. DR BioCyc; MetaCyc:ENSG00000137760-MONOMER; -. DR BRENDA; 2.1.1.229; 2681. DR PathwayCommons; Q96BT7; -. DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol. DR SignaLink; Q96BT7; -. DR BioGRID-ORCS; 91801; 17 hits in 1168 CRISPR screens. DR ChiTaRS; ALKBH8; human. DR EvolutionaryTrace; Q96BT7; -. DR GenomeRNAi; 91801; -. DR Pharos; Q96BT7; Tbio. DR PRO; PR:Q96BT7; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96BT7; Protein. DR Bgee; ENSG00000137760; Expressed in calcaneal tendon and 169 other cell types or tissues. DR ExpressionAtlas; Q96BT7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IEA:InterPro. DR GO; GO:0005506; F:iron ion binding; ISS: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; IBA:GO_Central. DR GO; GO:0016300; F:tRNA (uridine) methyltransferase activity; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0030488; P:tRNA methylation; IDA: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; 2.60.120.1520; -; 1. DR Gene3D; 3.30.70.330; -; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR027450; AlkB-like. 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 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 Genevisible; Q96BT7; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW Intellectual disability; 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_0000337125" FT DOMAIN 43..120 FT /note="RRM" FT DOMAIN 220..337 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT REGION 411..664 FT /note="Methyltransferase domain" FT REGION 515..575 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 515..534 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 535..575 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 227..229 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22065580" 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" 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" FT BINDING 242 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22065580" 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 ECO:0000305" FT BINDING 328 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22065580" FT BINDING 334 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:22065580" FT BINDING 341 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22065580" FT BINDING 343 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22065580" FT BINDING 349 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:22065580" FT VAR_SEQ 1 FT /note="M -> MFAM (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039159" FT VAR_SEQ 215..224 FT /note="GYIKHKPDQM -> AEKNLEVGIH (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033925" FT VAR_SEQ 225..664 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033926" FT VAR_SEQ 234..238 FT /note="GIPAH -> DCHGF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033927" FT VAR_SEQ 239..664 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033928" FT VARIANT 554..664 FT /note="Missing (in MRT71; missing tRNA wobble uridine FT modification)" FT /evidence="ECO:0000269|PubMed:31079898" FT /id="VAR_083119" FT CONFLICT 210 FT /note="K -> R (in Ref. 2; BAC04566)" FT /evidence="ECO:0000305" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:2CQ2" FT TURN 30..34 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:3THP" FT STRAND 43..48 FT /evidence="ECO:0007829|PDB:3THT" FT HELIX 52..54 FT /evidence="ECO:0007829|PDB:3THT" FT HELIX 58..66 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 71..75 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 81..89 FT /evidence="ECO:0007829|PDB:3THT" FT HELIX 90..99 FT /evidence="ECO:0007829|PDB:3THT" FT TURN 100..102 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 116..119 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 121..129 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 137..140 FT /evidence="ECO:0007829|PDB:3THT" FT HELIX 146..153 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:3THT" FT HELIX 202..214 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 222..229 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 235..238 FT /evidence="ECO:0007829|PDB:3THT" FT TURN 242..244 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 249..256 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 258..263 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 269..274 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 278..282 FT /evidence="ECO:0007829|PDB:3THT" FT HELIX 285..288 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 290..294 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 298..304 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 307..309 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 315..318 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 320..324 FT /evidence="ECO:0007829|PDB:3THT" FT STRAND 328..334 FT /evidence="ECO:0007829|PDB:3THT" FT TURN 346..348 FT /evidence="ECO:0007829|PDB:3THT" FT TURN 350..355 FT /evidence="ECO:0007829|PDB:3THT" SQ SEQUENCE 664 AA; 75208 MW; 4BE595D6757C2A43 CRC64; MDSNHQSNYK LSKTEKKFLR KQIKAKHTLL RHEGIETVSY ATQSLVVANG GLGNGVSRNQ LLPVLEKCGL VDALLMPPNK PYSFARYRTT EESKRAYVTL NGKEVVDDLG QKITLYLNFV EKVQWKELRP QALPPGLMVV EEIISSEEEK MLLESVDWTE DTDNQNSQKS LKHRRVKHFG YEFHYENNNV DKDKPLSGGL PDICESFLEK WLRKGYIKHK PDQMTINQYE PGQGIPAHID THSAFEDEIV SLSLGSEIVM DFKHPDGIAV PVMLPRRSLL VMTGESRYLW THGITCRKFD TVQASESLKS GIITSDVGDL TLSKRGLRTS FTFRKVRQTP CNCSYPLVCD SQRKETPPSF PESDKEASRL EQEYVHQVYE EIAGHFSSTR HTPWPHIVEF LKALPSGSIV ADIGCGNGKY LGINKELYMI GCDRSQNLVD ICRERQFQAF VCDALAVPVR SGSCDACISI AVIHHFATAE RRVAALQEIV RLLRPGGKAL IYVWAMEQEY NKQKSKYLRG NRNSQGKKEE MNSDTSVQRS LVEQMRDMGS RDSASSVPRI NDSQEGGCNS RQVSNSKLPV HVNRTSFYSQ DVLVPWHLKG NPDKGKPVEP FGPIGSQDPS PVFHRYYHVF REGELEGACR TVSDVRILQS YYDQGNWCVI LQKA //