ALKB8_HUMAN
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 03-AUG-2022, entry version 172.
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=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 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=5; 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}.
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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; CCDS73376.1; -. [Q96BT7-1]
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; 7.
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; Q96BT7; -.
DR PeptideAtlas; Q96BT7; -.
DR PRIDE; Q96BT7; -.
DR ProteomicsDB; 76112; -. [Q96BT7-1]
DR ProteomicsDB; 76113; -. [Q96BT7-2]
DR ProteomicsDB; 76114; -. [Q96BT7-3]
DR ProteomicsDB; 76115; -. [Q96BT7-4]
DR Antibodypedia; 18165; 161 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; ENSP00000397673.2; ENSG00000137760.15. [Q96BT7-4]
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 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; 996085at2759; -.
DR PhylomeDB; Q96BT7; -.
DR TreeFam; TF316056; -.
DR BioCyc; MetaCyc:ENSG00000137760-MON; -.
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; 13 hits in 1090 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 167 other tissues.
DR ExpressionAtlas; Q96BT7; baseline and differential.
DR Genevisible; Q96BT7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
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:Ensembl.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0106335; F:tRNA (carboxymethyluridine(34)-5-O)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0016300; F:tRNA (uracil) 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:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0030488; P:tRNA methylation; IDA:UniProtKB.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IDA:UniProtKB.
DR CDD; cd12431; RRM_ALKBH8; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR Gene3D; 3.40.50.150; -; 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; 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 SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
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
