ALKB5_HUMAN
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 03-AUG-2022, entry version 153.
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};
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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; 25.
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; Q6P6C2; -.
DR PeptideAtlas; Q6P6C2; -.
DR PRIDE; Q6P6C2; -.
DR ProteomicsDB; 67020; -. [Q6P6C2-2]
DR ProteomicsDB; 67021; -. [Q6P6C2-2]
DR Antibodypedia; 2003; 144 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 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; KSMMPYR; -.
DR OrthoDB; 722070at2759; -.
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 1083 CRISPR screens.
DR ChiTaRS; ALKBH5; human.
DR GenomeRNAi; 54890; -.
DR Pharos; Q6P6C2; Tbio.
DR PRO; PR:Q6P6C2; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6P6C2; protein.
DR Bgee; ENSG00000091542; Expressed in tibialis anterior and 179 other tissues.
DR ExpressionAtlas; Q6P6C2; baseline and differential.
DR Genevisible; Q6P6C2; HS.
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:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0006406; P:mRNA export from nucleus; IMP:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IMP:UniProtKB.
DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; IDA:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR Gene3D; 2.60.120.590; -; 1.
DR InterPro; IPR027450; AlkB-like.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR032860; ALKBH5.
DR PANTHER; PTHR32074; PTHR32074; 2.
DR Pfam; PF13532; 2OG-FeII_Oxy_2; 1.
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 N(6)-
FT 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 N(6)-
FT 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 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
