ID ALKB5_HUMAN Reviewed; 394 AA. AC Q6P6C2; B4DVJ4; D3DXC6; Q9NXD6; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 2. DT 27-MAR-2024, entry version 162. DE RecName: Full=RNA demethylase ALKBH5 {ECO:0000303|PubMed:24616105}; DE EC=1.14.11.53 {ECO:0000269|PubMed:24616105}; DE AltName: Full=Alkylated DNA repair protein alkB homolog 5; DE AltName: Full=Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5; GN Name=ALKBH5; Synonyms=ABH5, OFOXD1; 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 [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Hepatoma, and Spleen; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [3] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [6] RP TISSUE 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-69 AND SER-361, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; TYR-71 AND SER-374, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-132, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=21264265; DOI=10.1371/journal.pone.0016210; RA Thalhammer A., Bencokova Z., Poole R., Loenarz C., Adam J., O'Flaherty L., RA Schodel J., Mole D., Giaslakiotis K., Schofield C.J., Hammond E.M., RA Ratcliffe P.J., Pollard P.J.; RT "Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and RT a direct target of hypoxia-inducible factor 1alpha (HIF-1alpha)."; RL PLoS ONE 6:E16210-E16210(2011). RN [13] RP INDUCTION. RX PubMed=22761421; DOI=10.1074/jbc.m112.378281; RA Karkhanis V., Wang L., Tae S., Hu Y.J., Imbalzano A.N., Sif S.; RT "Protein arginine methyltransferase 7 regulates cellular response to DNA RT damage by methylating promoter histones H2A and H4 of the polymerase delta RT catalytic subunit gene, POLD1."; RL J. Biol. Chem. 287:29801-29814(2012). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64 AND SER-361, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-204 AND HIS-266. 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-359, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [19] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-328, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 74-294 IN COMPLEX WITH RP ALPHA-KETOGLUTARATE AND MANGANESE, COFACTOR, FUNCTION, SUBUNIT, AND RP MUTAGENESIS OF ARG-130; TYR-139 AND GLU-153. RX PubMed=24778178; DOI=10.1074/jbc.m114.550350; RA Xu C., Liu K., Tempel W., Demetriades M., Aik W., Schofield C.J., Min J.; RT "Structures of human ALKBH5 demethylase reveal a unique binding mode for RT specific single-stranded N6-methyladenosine RNA demethylation."; RL J. Biol. Chem. 289:17299-17311(2014). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 66-292 IN COMPLEX WITH RP ALPHA-KETOGLUTARATE AND MANGANESE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, RP AND MUTAGENESIS OF ARG-130; LYS-132; TYR-139; TYR-141; TYR-195; HIS-204; RP 209-HIS-ILE-210; 232-PHE--PHE-234; ARG-277 AND ARG-283. RX PubMed=24616105; DOI=10.1074/jbc.m113.546168; RA Feng C., Liu Y., Wang G., Deng Z., Zhang Q., Wu W., Tong Y., Cheng C., RA Chen Z.; RT "Crystal structures of the human RNA demethylase Alkbh5 reveal basis for RT substrate recognition."; RL J. Biol. Chem. 289:11571-11583(2014). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 66-292 IN COMPLEX WITH MANGANESE RP AND INHIBITOR, FUNCTION, AND COFACTOR. RX PubMed=24489119; DOI=10.1093/nar/gku085; RA Aik W., Scotti J.S., Choi H., Gong L., Demetriades M., Schofield C.J., RA McDonough M.A.; RT "Structure of human RNA N6-methyladenine demethylase ALKBH5 provides RT insights into its mechanisms of nucleic acid recognition and RT demethylation."; RL Nucleic Acids Res. 42:4741-4754(2014). 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:23177736, PubMed:24489119, PubMed:24616105, CC PubMed:24778178). Can also demethylate N(6)-methyladenosine in single- CC stranded DNA (in vitro) (PubMed:24616105). Requires molecular oxygen, CC alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, CC PubMed:24489119, PubMed:24616105, PubMed:24778178). Demethylation of CC m6A mRNA affects mRNA processing and export (PubMed:23177736). 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 (By CC similarity). {ECO:0000250|UniProtKB:Q3TSG4, CC ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, CC ECO:0000269|PubMed:24489119, ECO:0000269|PubMed:24616105, CC ECO:0000269|PubMed:24778178}. 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:0000269|PubMed:24616105}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:24489119, ECO:0000269|PubMed:24616105, CC ECO:0000269|PubMed:24778178}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:24489119, CC ECO:0000305|PubMed:24616105, ECO:0000305|PubMed:24778178}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24778178}. CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:21264265, CC ECO:0000269|PubMed:23177736}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=2; CC IsoId=Q6P6C2-2; Sequence=Displayed; CC Name=1; CC IsoId=Q6P6C2-1; Sequence=VSP_019130; CC Name=3; CC IsoId=Q6P6C2-3; Sequence=VSP_044226; CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in lung, CC followed by testis, pancreas, spleen and ovary. CC {ECO:0000269|PubMed:17979886}. CC -!- INDUCTION: By hypoxia, directly activated by HIF1A. Expression is CC regulated by PRMT7. {ECO:0000269|PubMed:21264265, CC ECO:0000269|PubMed:22761421}. CC -!- SIMILARITY: Belongs to the alkB family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91078.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AK000315; BAA91078.1; ALT_INIT; mRNA. DR EMBL; AK301107; BAG62706.1; -; mRNA. DR EMBL; AC087164; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC109515; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471196; EAW55661.1; -; Genomic_DNA. DR EMBL; CH471196; EAW55662.1; -; Genomic_DNA. DR EMBL; BC062339; AAH62339.1; -; mRNA. DR CCDS; CCDS42272.1; -. [Q6P6C2-2] DR RefSeq; NP_060228.3; NM_017758.3. [Q6P6C2-2] DR PDB; 4NJ4; X-ray; 2.02 A; A/B=66-292. DR PDB; 4NRM; X-ray; 2.17 A; A=66-292. DR PDB; 4NRO; X-ray; 2.30 A; A=66-292. DR PDB; 4NRP; X-ray; 1.80 A; A=66-292. DR PDB; 4NRQ; X-ray; 2.50 A; A=66-292. DR PDB; 4O61; X-ray; 1.90 A; A/B=74-294. DR PDB; 4O7X; X-ray; 1.78 A; A=66-292. DR PDB; 4OCT; X-ray; 2.28 A; A/B=74-294. DR PDB; 7V4G; X-ray; 2.10 A; A/B/C=74-292. DR PDB; 7WKV; X-ray; 2.10 A; A/C/E=74-292. DR PDB; 7WL0; X-ray; 2.50 A; A/C/E/G/I=74-292. DR PDBsum; 4NJ4; -. DR PDBsum; 4NRM; -. DR PDBsum; 4NRO; -. DR PDBsum; 4NRP; -. DR PDBsum; 4NRQ; -. DR PDBsum; 4O61; -. DR PDBsum; 4O7X; -. DR PDBsum; 4OCT; -. DR PDBsum; 7V4G; -. DR PDBsum; 7WKV; -. DR PDBsum; 7WL0; -. DR AlphaFoldDB; Q6P6C2; -. DR SMR; Q6P6C2; -. DR BioGRID; 120237; 50. DR IntAct; Q6P6C2; 9. DR MINT; Q6P6C2; -. DR STRING; 9606.ENSP00000382091; -. DR BindingDB; Q6P6C2; -. DR ChEMBL; CHEMBL3621037; -. DR iPTMnet; Q6P6C2; -. DR PhosphoSitePlus; Q6P6C2; -. DR BioMuta; ALKBH5; -. DR DMDM; 408359959; -. DR EPD; Q6P6C2; -. DR jPOST; Q6P6C2; -. DR MassIVE; Q6P6C2; -. DR MaxQB; Q6P6C2; -. DR PaxDb; 9606-ENSP00000382091; -. DR PeptideAtlas; Q6P6C2; -. DR ProteomicsDB; 67020; -. [Q6P6C2-2] DR ProteomicsDB; 67021; -. [Q6P6C2-2] DR Pumba; Q6P6C2; -. DR Antibodypedia; 2003; 158 antibodies from 25 providers. DR DNASU; 54890; -. DR Ensembl; ENST00000399138.5; ENSP00000382091.4; ENSG00000091542.9. [Q6P6C2-2] DR GeneID; 54890; -. DR KEGG; hsa:54890; -. DR MANE-Select; ENST00000399138.5; ENSP00000382091.4; NM_017758.4; NP_060228.3. DR UCSC; uc010cpw.4; human. [Q6P6C2-2] DR AGR; HGNC:25996; -. DR CTD; 54890; -. DR DisGeNET; 54890; -. DR GeneCards; ALKBH5; -. DR HGNC; HGNC:25996; ALKBH5. DR HPA; ENSG00000091542; Tissue enhanced (skeletal). DR MIM; 613303; gene. DR neXtProt; NX_Q6P6C2; -. DR OpenTargets; ENSG00000091542; -. DR PharmGKB; PA142671230; -. DR VEuPathDB; HostDB:ENSG00000091542; -. DR eggNOG; KOG4176; Eukaryota. DR GeneTree; ENSGT00390000009298; -. DR HOGENOM; CLU_047472_1_0_1; -. DR InParanoid; Q6P6C2; -. DR OMA; ENYWRRD; -. DR OrthoDB; 179931at2759; -. DR PhylomeDB; Q6P6C2; -. DR TreeFam; TF329212; -. DR BRENDA; 1.14.11.53; 2681. DR PathwayCommons; Q6P6C2; -. DR Reactome; R-HSA-73943; Reversal of alkylation damage by DNA dioxygenases. DR SignaLink; Q6P6C2; -. DR BioGRID-ORCS; 54890; 14 hits in 1159 CRISPR screens. DR ChiTaRS; ALKBH5; human. DR GenomeRNAi; 54890; -. DR Pharos; Q6P6C2; Tchem. DR PRO; PR:Q6P6C2; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q6P6C2; Protein. DR Bgee; ENSG00000091542; Expressed in tibialis anterior and 181 other cell types or tissues. DR ExpressionAtlas; Q6P6C2; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0042382; C:paraspeckles; IDA:UniProtKB. DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:UniProtKB. DR GO; GO:1990931; F:mRNA N6-methyladenosine dioxygenase activity; IDA:UniProtKB. DR GO; GO:0035515; F:oxidative RNA demethylase activity; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0046630; P:gamma-delta T cell proliferation; IEA:Ensembl. DR GO; GO:0061157; P:mRNA destabilization; IDA:UniProt. DR GO; GO:0006406; P:mRNA export from nucleus; IMP:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IMP:UniProtKB. DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; IDA:UniProtKB. DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; IDA:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR Gene3D; 2.60.120.590; Alpha-ketoglutarate-dependent dioxygenase AlkB-like; 1. DR InterPro; IPR027450; AlkB-like. DR InterPro; IPR037151; AlkB-like_sf. DR InterPro; IPR032860; ALKBH5. DR PANTHER; PTHR32074; RNA DEMETHYLASE ALKBH5; 1. DR PANTHER; PTHR32074:SF2; RNA DEMETHYLASE ALKBH5; 1. DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR Genevisible; Q6P6C2; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Coiled coil; KW Differentiation; Dioxygenase; Iron; Isopeptide bond; Metal-binding; KW Methylation; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; KW Spermatogenesis; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..394 FT /note="RNA demethylase ALKBH5" FT /id="PRO_0000239283" FT REGION 1..26 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 48..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 299..394 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 67..116 FT /evidence="ECO:0000255" FT COMPBIAS 56..83 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 316..353 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 193..195 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:24778178" FT BINDING 204 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:24616105, FT ECO:0000305|PubMed:24778178" FT BINDING 206 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:24616105, FT ECO:0000305|PubMed:24778178" FT BINDING 266 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:24616105, FT ECO:0000305|PubMed:24778178" FT BINDING 277 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:24778178" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 69 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 71 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 132 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 359 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 361 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 371 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3TSG4" FT MOD_RES 374 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 384 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3TSG4" FT CROSSLNK 328 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..32 FT /note="MAAASGYTDLREKLKSMTSRDNYKAGSREAAA -> MRRCWRPCPAGRGEGG FT GGRSP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044226" FT VAR_SEQ 386..394 FT /note="ARKVKMRRH -> GNSGSSLRSGNSGSSLRSCPSFCFEGFVFVHWGVFVFCF FT LFFLILYIFPWFCCLLGLKNRIGQDLGSHILGIPPGWKGCWHQ (in isoform 1)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019130" FT MUTAGEN 130 FT /note="R->A: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:24616105, FT ECO:0000269|PubMed:24778178" FT MUTAGEN 132 FT /note="K->A: No effect on catalytic activity with FT N(6)-methyladenosine in single-stranded DNA." FT /evidence="ECO:0000269|PubMed:24616105" FT MUTAGEN 139 FT /note="Y->A: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:24616105, FT ECO:0000269|PubMed:24778178" FT MUTAGEN 141 FT /note="Y->A: Abolishes catalytic activity with FT N(6)-methyladenosine in single-stranded DNA." FT /evidence="ECO:0000269|PubMed:24616105" FT MUTAGEN 153 FT /note="E->A: No effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:24778178" FT MUTAGEN 195 FT /note="Y->A: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:24616105" FT MUTAGEN 204 FT /note="H->A: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:23177736, FT ECO:0000269|PubMed:24616105" FT MUTAGEN 209..210 FT /note="HI->AA: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:24616105" FT MUTAGEN 232..234 FT /note="FQF->DDE: Impaired catalytic activity." FT /evidence="ECO:0000269|PubMed:24616105" FT MUTAGEN 266 FT /note="H->A: Impaired catalytic activity." FT /evidence="ECO:0000269|PubMed:23177736" FT MUTAGEN 277 FT /note="R->A: Abolishes catalytic activity; when associated FT with A-283." FT /evidence="ECO:0000269|PubMed:24616105" FT MUTAGEN 283 FT /note="R->A: Abolishes catalytic activity; when associated FT with A-277." FT /evidence="ECO:0000269|PubMed:24616105" FT CONFLICT 1 FT /note="M -> L (in Ref. 1; BAA91078)" FT /evidence="ECO:0000305" FT HELIX 75..86 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 89..93 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 97..115 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 124..127 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 130..137 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 139..141 FT /evidence="ECO:0007829|PDB:4NJ4" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:7V4G" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:7WKV" FT STRAND 152..155 FT /evidence="ECO:0007829|PDB:4NJ4" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 166..171 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 173..178 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 189..195 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 201..204 FT /evidence="ECO:0007829|PDB:4O7X" FT TURN 208..210 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 215..219 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 224..228 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 231..233 FT /evidence="ECO:0007829|PDB:4O7X" FT TURN 236..238 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 243..248 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 252..256 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 258..262 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 266..268 FT /evidence="ECO:0007829|PDB:4O7X" FT HELIX 270..272 FT /evidence="ECO:0007829|PDB:4O7X" FT STRAND 277..283 FT /evidence="ECO:0007829|PDB:4O7X" SQ SEQUENCE 394 AA; 44256 MW; DEB7BF8770BDB3A0 CRC64; MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP YPVSGAKRKY QEDSDPERSD YEEQQLQKEE EARKVKSGIR QMRLFSQDEC AKIEARIDEV VSRAEKGLYN EHTVDRAPLR NKYFFGEGYT YGAQLQKRGP GQERLYPPGD VDEIPEWVHQ LVIQKLVEHR VIPEGFVNSA VINDYQPGGC IVSHVDPIHI FERPIVSVSF FSDSALCFGC KFQFKPIRVS EPVLSLPVRR GSVTVLSGYA ADEITHCIRP QDIKERRAVI ILRKTRLDAP RLETKSLSSS VLPPSYASDR LSGNNRDPAL KPKRSHRKAD PDAAHRPRIL EMDKEENRRS VLLPTHRRRG SFSSENYWRK SYESSEDCSE AAGSPARKVK MRRH //