ID TET2_HUMAN Reviewed; 2002 AA. AC Q6N021; B5MDU0; Q2TB88; Q3LIB8; Q96JX5; Q9HCM6; Q9NXW0; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 16-JUN-2009, sequence version 3. DT 28-JAN-2026, entry version 164. DE RecName: Full=Methylcytosine dioxygenase TET2; DE EC=1.14.11.80 {ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:32518946}; GN Name=TET2; Synonyms=KIAA1546; ORFNames=Nbla00191; 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] (ISOFORM 2), AND VARIANT MET-218. RC TISSUE=Fetal kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 301-2002 (ISOFORM 2). RC TISSUE=Adipose tissue, and Placenta; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 791-2002 (ISOFORM 3). RC TISSUE=Neuroblastoma; RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5; RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S., RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S., RA Hirato J., Nakagawara A.; RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the RT genesis and biology of neuroblastoma."; RL Cancer Lett. 197:63-68(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1198-2002 (ISOFORM 1), AND RP VARIANT VAL-1762. 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1319-2002 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10997877; DOI=10.1093/dnares/7.4.271; RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:273-281(2000). RN [7] RP IDENTIFICATION, AND TISSUE SPECIFICITY. RX PubMed=12646957; DOI=10.1038/sj.leu.2402834; RA Lorsbach R.B., Moore J., Mathew S., Raimondi S.C., Mukatira S.T., RA Downing J.R.; RT "TET1, a member of a novel protein family, is fused to MLL in acute myeloid RT leukemia containing the t(10;11)(q22;q23)."; RL Leukemia 17:637-641(2003). RN [8] 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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [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 [10] RP INTERACTION WITH DCAF1. RX PubMed=24357321; DOI=10.1126/science.1244587; RA Yu C., Zhang Y.L., Pan W.W., Li X.M., Wang Z.W., Ge Z.J., Zhou J.J., RA Cang Y., Tong C., Sun Q.Y., Fan H.Y.; RT "CRL4 complex regulates mammalian oocyte survival and reprogramming by RT activation of TET proteins."; RL Science 342:1518-1521(2013). RN [11] RP INTERACTION WITH DCAF1, MONOUBIQITINATION AT LYS-1299, SUBCELLULAR RP LOCATION, CHARACTERIZATION OF VARIANTS LEU-1287; ARG-1291; ASN-1299; RP GLU-1299; GLY-1302 AND GLY-1318, AND MUTAGENESIS OF SER-1292; CYS-1298 AND RP PHE-1300. RX PubMed=25557551; DOI=10.1016/j.molcel.2014.12.002; RA Nakagawa T., Lv L., Nakagawa M., Yu Y., Yu C., D'Alessio A.C., Nakayama K., RA Fan H.Y., Chen X., Xiong Y.; RT "CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of RT TET dioxygenases."; RL Mol. Cell 57:247-260(2015). RN [12] RP INVOLVEMENT IN MYELOID MALIGNANCIES, AND VARIANTS PHE-34; ASN-145; HIS-174; RP SER-312; PHE-460; GLY-666; HIS-867; SER-941; VAL-1073; PRO-1084; TYR-1135; RP CYS-1204; TRP-1214; VAL-1242; SER-1245; CYS-1261; HIS-1261; PHE-1417; RP LEU-1718; SER-1723; ASP-1757; ARG-1811; LEU-1828; THR-1873; ARG-1881; RP ALA-1900; VAL-1919; HIS-1926; SER-1941; HIS-1966; MET-1974 AND LYS-2000. RX PubMed=19420352; DOI=10.1182/blood-2009-03-210039; RA Abdel-Wahab O., Mullally A., Hedvat C., Garcia-Manero G., Patel J., RA Wadleigh M., Malinge S., Yao J., Kilpivaara O., Bhat R., Huberman K., RA Thomas S., Dolgalev I., Heguy A., Paietta E., Le Beau M.M., Beran M., RA Tallman M.S., Ebert B.L., Kantarjian H.M., Stone R.M., Gilliland D.G., RA Crispino J.D., Levine R.L.; RT "Genetic characterization of TET1, TET2, and TET3 alterations in myeloid RT malignancies."; RL Blood 114:144-147(2009). RN [13] RP INVOLVEMENT IN MDS, INVOLVEMENT IN MYELOPROLIFERATIVE DISORDERS, AND RP VARIANTS THR-308; LEU-399; THR-817; HIS-867; PRO-1084; THR-1167; LEU-1287; RP ASN-1299; GLY-1302; GLY-1318; LEU-1718; THR-1873 AND ASP-1913. RX PubMed=19372255; DOI=10.1182/blood-2009-02-205690; RA Jankowska A.M., Szpurka H., Tiu R.V., Makishima H., Afable M., Huh J., RA O'Keefe C.L., Ganetzky R., McDevitt M.A., Maciejewski J.P.; RT "Loss of heterozygosity 4q24 and TET2 mutations associated with RT myelodysplastic/myeloproliferative neoplasms."; RL Blood 113:6403-6410(2009). RN [14] RP INVOLVEMENT IN SYSTEMIC MASTOCYTOSIS, AND VARIANT ARG-1881. RX PubMed=19262599; DOI=10.1038/leu.2009.37; RA Tefferi A., Levine R.L., Lim K.H., Abdel-Wahab O., Lasho T.L., Patel J., RA Finke C.M., Mullally A., Li C.Y., Pardanani A., Gilliland D.G.; RT "Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and RT FIP1L1-PDGFRA correlates."; RL Leukemia 23:900-904(2009). RN [15] RP INVOLVEMENT IN MYELOPROLIFERATIVE DISORDERS, AND VARIANTS ARG-1242 AND RP THR-1873. RX PubMed=19262601; DOI=10.1038/leu.2009.47; RA Tefferi A., Pardanani A., Lim K.H., Abdel-Wahab O., Lasho T.L., Patel J., RA Gangat N., Finke C.M., Schwager S., Mullally A., Li C.-Y., Hanson C.A., RA Mesa R., Bernard O., Delhommeau F., Vainchenker W., Gilliland D.G., RA Levine R.L.; RT "TET2 mutations and their clinical correlates in polycythemia vera, RT essential thrombocythemia and myelofibrosis."; RL Leukemia 23:905-911(2009). RN [16] RP INVOLVEMENT IN MDS, FUNCTION, TISSUE SPECIFICITY, AND VARIANTS ARG-29; RP PHE-34; HIS-123; MET-218; ASP-355; LEU-363; ARG-429; HIS-867; ARG-924; RP ARG-949; PRO-1084; TRP-1214; LEU-1261; PHE-1285 DEL; ARG-1291; TRP-1396; RP ARG-1398; ILE-1701; TRP-1721; SER-1723; VAL-1762; ARG-1778; THR-1873; RP ARG-1875; GLN-1881; SER-1896; 1911-LYS--LEU-1916 DEL; ASP-1913 AND RP LEU-1962. RX PubMed=19483684; DOI=10.1038/ng.391; RA Langemeijer S.M.C., Kuiper R.P., Berends M., Knops R., Aslanyan M.G., RA Massop M., Stevens-Linders E., van Hoogen P., van Kessel A.G., RA Raymakers R.A.P., Kamping E.J., Verhoef G.E., Verburgh E., Hagemeijer A., RA Vandenberghe P., de Witte T., van der Reijden B.A., Jansen J.H.; RT "Acquired mutations in TET2 are common in myelodysplastic syndromes."; RL Nat. Genet. 41:838-842(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-1107, 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 [18] RP FUNCTION, INVOLVEMENT IN MDS, AND INVOLVEMENT IN MYELOPROLIFERATIVE RP DISORDERS. RX PubMed=21057493; DOI=10.1038/nature09586; RA Ko M., Huang Y., Jankowska A.M., Pape U.J., Tahiliani M., Bandukwala H.S., RA An J., Lamperti E.D., Koh K.P., Ganetzky R., Liu X.S., Aravind L., RA Agarwal S., Maciejewski J.P., Rao A.; RT "Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant RT TET2."; RL Nature 468:839-843(2010). RN [19] RP FUNCTION. RX PubMed=21817016; DOI=10.1126/science.1210944; RA He Y.F., Li B.Z., Li Z., Liu P., Wang Y., Tang Q., Ding J., Jia Y., RA Chen Z., Li L., Sun Y., Li X., Dai Q., Song C.X., Zhang K., He C., Xu G.L.; RT "Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in RT mammalian DNA."; RL Science 333:1303-1307(2011). RN [20] RP FUNCTION, AND INTERACTION WITH HCFC1 AND OGT. RX PubMed=23353889; DOI=10.1038/emboj.2012.357; RA Deplus R., Delatte B., Schwinn M.K., Defrance M., Mendez J., Murphy N., RA Dawson M.A., Volkmar M., Putmans P., Calonne E., Shih A.H., Levine R.L., RA Bernard O., Mercher T., Solary E., Urh M., Daniels D.L., Fuks F.; RT "TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and RT SET1/COMPASS."; RL EMBO J. 32:645-655(2013). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75; SER-99; SER-1107 AND RP SER-1109, AND 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 [22] RP FUNCTION, INTERACTION WITH OGT, AND MUTAGENESIS OF HIS-1382 AND ASP-1384. RX PubMed=23222540; DOI=10.1038/nature11742; RA Chen Q., Chen Y., Bian C., Fujiki R., Yu X.; RT "TET2 promotes histone O-GlcNAcylation during gene transcription."; RL Nature 493:561-564(2013). RN [23] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1682, 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 [24] RP INTERACTION WITH PROSER1. RX PubMed=34667079; DOI=10.26508/lsa.202101228; RA Wang X., Rosikiewicz W., Sedkov Y., Martinez T., Hansen B.S., Schreiner P., RA Christensen J., Xu B., Pruett-Miller S.M., Helin K., Herz H.M.; RT "PROSER1 mediates TET2 O-GlcNAcylation to regulate DNA demethylation on RT UTX-dependent enhancers and CpG islands."; RL Life. Sci Alliance 5:0-0(2022). RN [25] RP ACETYLATION, AND DEACETYLATION BY HDAC6. RX PubMed=39567688; DOI=10.1038/s41586-024-08248-5; RA Jin J., Meng T., Yu Y., Wu S., Jiao C.C., Song S., Li Y.X., Zhang Y., RA Zhao Y.Y., Li X., Wang Z., Liu Y.F., Huang R., Qin J., Chen Y., Cao H., RA Tan X., Ge X., Jiang C., Xue J., Yuan J., Wu D., Wu W., Jiang C.Z., RA Wang P.; RT "Human HDAC6 senses valine abundancy to regulate DNA damage."; RL Nature 0:0-0(2024). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 1129-1480 AND 1844-1936 IN RP COMPLEX WITH DNA; IRON; N-OXALYOLGLYCINE AND ZINC, CATALYTIC ACTIVITY, RP FUNCTION, CHARACTERIZATION OF VARIANTS ARG-1291; GLU-1299; MET-1896 AND RP PHE-1898, AND MUTAGENESIS OF ARG-1261; ARG-1262; SER-1290; RP 1291-TRP--ASN-1296; 1293-MET-TYR-1294; TYR-1295; SER-1303; HIS-1382; RP ASP-1384; ASN-1387; TYR-1902 AND HIS-1904. RX PubMed=24315485; DOI=10.1016/j.cell.2013.11.020; RA Hu L., Li Z., Cheng J., Rao Q., Gong W., Liu M., Shi Y.G., Zhu J., Wang P., RA Xu Y.; RT "Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC RT oxidation."; RL Cell 155:1545-1555(2013). RN [27] RP VARIANTS VAL-1175; 1237-PRO--SER-1239 DEL; GLU-1299; GLY-1302; TRP-1869; RP PRO-1872; THR-1873; MET-1896 AND PHE-1898. RX PubMed=19474426; DOI=10.1056/nejmoa0810069; RA Delhommeau F., Dupont S., Della Valle V., James C., Trannoy S., Masse A., RA Kosmider O., Le Couedic J.-P., Robert F., Alberdi A., Lecluse Y., Plo I., RA Dreyfus F.J., Marzac C., Casadevall N., Lacombe C., Romana S.P., Dessen P., RA Soulier J., Viguie F., Fontenay M., Vainchenker W., Bernard O.A.; RT "Mutation in TET2 in myeloid cancers."; RL N. Engl. J. Med. 360:2289-2301(2009). RN [28] RP INVOLVEMENT IN IMD75, VARIANTS IMD75 ARG-1382 AND 1632-GLN--ILE-2002 DEL, RP CHARACTERIZATION OF VARIANTS IMD75 ARG-1382 AND 1632-GLN--ILE-2002 DEL, RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32518946; DOI=10.1182/blood.2020005844; RA Stremenova Spegarova J., Lawless D., Mohamad S.M.B., Engelhardt K.R., RA Doody G., Shrimpton J., Rensing-Ehl A., Ehl S., Rieux-Laucat F., Cargo C., RA Griffin H., Mikulasova A., Acres M., Morgan N.V., Poulter J.A., RA Sheridan E.G., Chetcuti P., O'Riordan S., Anwar R., Carter C.R., RA Przyborski S., Windebank K., Cant A.J., Lako M., Bacon C.M., Savic S., RA Hambleton S.; RT "Germline TET2 loss of function causes childhood immunodeficiency and RT lymphoma."; RL Blood 136:1055-1066(2020). CC -!- FUNCTION: Dioxygenase that catalyzes the conversion of the modified CC genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) CC and plays a key role in active DNA demethylation. Has a preference for CC 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent CC conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC CC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC CC probably constitutes the first step in cytosine demethylation. CC Methylation at the C5 position of cytosine bases is an epigenetic CC modification of the mammalian genome which plays an important role in CC transcriptional regulation. In addition to its role in DNA CC demethylation, also involved in the recruitment of the O-GlcNAc CC transferase OGT to CpG-rich transcription start sites of active genes, CC thereby promoting histone H2B GlcNAcylation by OGT. CC {ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493, CC ECO:0000269|PubMed:21817016, ECO:0000269|PubMed:23222540, CC ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24315485, CC ECO:0000269|PubMed:32518946}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5-methyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a CC 5-hydroxymethyl-2'-deoxycytidine in DNA + succinate + CO2; CC Xref=Rhea:RHEA:52636, Rhea:RHEA-COMP:11370, Rhea:RHEA-COMP:13315, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:85454, ChEBI:CHEBI:136731; CC EC=1.14.11.80; Evidence={ECO:0000269|PubMed:24315485, CC ECO:0000269|PubMed:32518946}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52637; CC Evidence={ECO:0000269|PubMed:32518946}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5-hydroxymethyl-2'-deoxycytidine in DNA + 2-oxoglutarate + CC O2 = a 5-formyl-2'-deoxycytidine in DNA + succinate + CO2 + H2O; CC Xref=Rhea:RHEA:53828, Rhea:RHEA-COMP:13315, Rhea:RHEA-COMP:13656, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:136731, CC ChEBI:CHEBI:137731; EC=1.14.11.80; CC Evidence={ECO:0000269|PubMed:24315485}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5-formyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a CC 5-carboxyl-2'-deoxycytidine in DNA + succinate + CO2 + H(+); CC Xref=Rhea:RHEA:53832, Rhea:RHEA-COMP:13656, Rhea:RHEA-COMP:13657, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:137731, CC ChEBI:CHEBI:137732; EC=1.14.11.80; CC Evidence={ECO:0000269|PubMed:24315485}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:24315485}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:24315485}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:24315485}; CC Note=Binds 3 zinc ions per subunit. The zinc ions have a structural CC role (PubMed:24315485). {ECO:0000269|PubMed:24315485}; CC -!- SUBUNIT: Interacts with HCFC1 (PubMed:23353889). Interacts with OGT CC (PubMed:23222540, PubMed:23353889). Interacts with PROSER1; this CC interaction mediates TET2 O-GlcNAcylation and stability by promoting CC the interaction between OGT and TET2 (PubMed:34667079). Directly CC interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) CC E3 ubiquitin-protein ligase complex (PubMed:24357321, PubMed:25557551). CC {ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:23353889, CC ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:24357321, CC ECO:0000269|PubMed:25557551, ECO:0000269|PubMed:34667079}. CC -!- INTERACTION: CC Q6N021; P22607: FGFR3; NbExp=3; IntAct=EBI-310727, EBI-348399; CC Q6N021; P06396: GSN; NbExp=3; IntAct=EBI-310727, EBI-351506; CC Q6N021; O15294: OGT; NbExp=7; IntAct=EBI-310727, EBI-539828; CC Q6N021; P29590: PML; NbExp=2; IntAct=EBI-310727, EBI-295890; CC Q6N021; P04279: SEMG1; NbExp=2; IntAct=EBI-310727, EBI-953955; CC Q6N021; P19544: WT1; NbExp=9; IntAct=EBI-310727, EBI-2320534; CC Q6N021-1; O15294: OGT; NbExp=5; IntAct=EBI-20717492, EBI-539828; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25557551}. Chromosome CC {ECO:0000269|PubMed:25557551}. Note=Localization to chromatin depends CC upon monoubiquitination at Lys-1299. {ECO:0000269|PubMed:25557551}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6N021-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6N021-2; Sequence=VSP_032283, VSP_032284; CC Name=3; CC IsoId=Q6N021-3; Sequence=VSP_032282, VSP_032285; CC -!- TISSUE SPECIFICITY: Broadly expressed. Highly expressed in CC hematopoietic cells; highest expression observed in granulocytes. CC Expression is reduced in granulocytes from peripheral blood of patients CC affected by myelodysplastic syndromes. {ECO:0000269|PubMed:12646957, CC ECO:0000269|PubMed:19483684}. CC -!- PTM: May be glycosylated. It is unclear whether interaction with OGT CC leads to GlcNAcylation. According to a report, it is not GlcNAcylated CC by OGT (PubMed:23353889). In contrast, another group reports CC GlcNAcylation by OGT in mouse ortholog. {ECO:0000269|PubMed:23353889}. CC -!- PTM: Monoubiquitinated at Lys-1299 by the DCX (DDB1-CUL4-X-box) E3 CC ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1- CC DCAF1/VPRBP complex; this modification promotes binding to DNA. CC {ECO:0000269|PubMed:25557551}. CC -!- PTM: Acetylated (PubMed:39567688). Deacetylase HDAC6 acts as a valine CC sensor by binding to valine through its primate-specific SE14 repeat CC region and deacetylates TET2 following valine deprivation which CC promotes TET2-dependent DNA demethylation (PubMed:39567688). CC {ECO:0000269|PubMed:39567688}. CC -!- DISEASE: Note=TET2 is frequently mutated in myeloproliferative CC disorders (MPD). These constitute a heterogeneous group of disorders, CC also known as myeloproliferative diseases or myeloproliferative CC neoplasms (MPN), characterized by cellular proliferation of one or more CC hematologic cell lines in the peripheral blood, distinct from acute CC leukemia. Included diseases are: essential thrombocythemia, CC polycythemia vera, primary myelofibrosis (chronic idiopathic CC myelofibrosis). Bone marrow samples from patients display uniformly low CC levels of hmC in genomic DNA compared to bone marrow samples from CC healthy controls as well as hypomethylation relative to controls at the CC majority of differentially methylated CpG sites. CC -!- DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative CC disorder characterized by abnormal proliferation of all hematopoietic CC bone marrow elements, erythroid hyperplasia, an absolute increase in CC total blood volume, but also by myeloid leukocytosis, thrombocytosis CC and splenomegaly. Note=The disease is caused by variants affecting the CC gene represented in this entry. CC -!- DISEASE: Note=TET2 is frequently mutated in systemic mastocytosis; also CC known as systemic mast cell disease. A condition with features in CC common with myeloproliferative diseases. It is a clonal disorder of the CC mast cell and its precursor cells. The clinical symptoms and signs of CC systemic mastocytosis are due to accumulation of clonally derived mast CC cells in different tissues, including bone marrow, skin, the CC gastrointestinal tract, the liver, and the spleen. CC -!- DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous CC group of closely related clonal hematopoietic disorders. All are CC characterized by a hypercellular or hypocellular bone marrow with CC impaired morphology and maturation, dysplasia of the myeloid, CC megakaryocytic and/or erythroid lineages, and peripheral blood CC cytopenias resulting from ineffective blood cell production. Included CC diseases are: refractory anemia (RA), refractory anemia with ringed CC sideroblasts (RARS), refractory anemia with excess blasts (RAEB), CC refractory cytopenia with multilineage dysplasia and ringed CC sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a CC myelodysplastic/myeloproliferative disease. MDS is considered a CC premalignant condition in a subgroup of patients that often progresses CC to acute myeloid leukemia (AML). {ECO:0000269|PubMed:19372255, CC ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. Bone marrow samples from patients display uniformly low levels CC of hmC in genomic DNA compared to bone marrow samples from healthy CC controls as well as hypomethylation relative to controls at the CC majority of differentially methylated CpG sites. CC -!- DISEASE: Immunodeficiency 75 with lymphoproliferation (IMD75) CC [MIM:619126]: An autosomal recessive immunologic disorder characterized CC by recurrent infections, mainly viral and affecting the respiratory CC tract, immunodeficieny, immune dysregulation, and the development of CC lymphoproliferative disorders, including lymphoma. CC {ECO:0000269|PubMed:32518946}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: 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 -!- SIMILARITY: Belongs to the TET family. {ECO:0000305}. CC -!- CAUTION: Subsequent steps in cytosine demethylation are subject to CC discussion. According to a first model cytosine demethylation occurs CC through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and CC subsequent replacement by unmethylated cytosine by the base excision CC repair system. According to another model, cytosine demethylation is CC rather mediated via conversion of 5hmC into 5fC and 5caC, followed by CC excision by TDG (PubMed:21817016). {ECO:0000305|PubMed:21817016}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA90898.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA90898.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA90898.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAB55391.1; 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; BX640738; CAE45851.1; -; mRNA. DR EMBL; AC004069; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC026029; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK000039; BAA90898.1; ALT_SEQ; mRNA. DR EMBL; AK027819; BAB55391.1; ALT_INIT; mRNA. DR EMBL; AB075496; BAE45750.1; -; mRNA. DR EMBL; BC110509; AAI10510.1; -; mRNA. DR EMBL; BC110510; AAI10511.2; -; mRNA. DR EMBL; AB046766; BAB13372.1; -; mRNA. DR CCDS; CCDS3666.1; -. [Q6N021-2] DR CCDS; CCDS47120.1; -. [Q6N021-1] DR RefSeq; NP_001120680.1; NM_001127208.3. [Q6N021-1] DR RefSeq; NP_060098.3; NM_017628.4. [Q6N021-2] DR RefSeq; XP_005263139.1; XM_005263082.4. [Q6N021-1] DR RefSeq; XP_024309870.1; XM_024454102.2. [Q6N021-1] DR RefSeq; XP_024309871.1; XM_024454103.2. [Q6N021-1] DR RefSeq; XP_047271797.1; XM_047415841.1. [Q6N021-3] DR RefSeq; XP_054206253.1; XM_054350278.1. [Q6N021-3] DR PDB; 4NM6; X-ray; 2.03 A; A=1129-1480, A=1844-1936. DR PDB; 5D9Y; X-ray; 1.97 A; A=1129-1480, A=1844-1936. DR PDB; 5DEU; X-ray; 1.80 A; A=1129-1480, A=1844-1935. DR PDB; 7NE3; X-ray; 2.26 A; A=1129-1480. DR PDB; 7NE6; X-ray; 2.30 A; A=1129-1480. DR PDB; 9HXV; X-ray; 1.90 A; A=1129-1480, A=1844-1936. DR PDBsum; 4NM6; -. DR PDBsum; 5D9Y; -. DR PDBsum; 5DEU; -. DR PDBsum; 7NE3; -. DR PDBsum; 7NE6; -. DR PDBsum; 9HXV; -. DR AlphaFoldDB; Q6N021; -. DR SMR; Q6N021; -. DR BioGRID; 120151; 146. DR CORUM; Q6N021; -. DR FunCoup; Q6N021; 1878. DR IntAct; Q6N021; 56. DR MINT; Q6N021; -. DR STRING; 9606.ENSP00000442788; -. DR BindingDB; Q6N021; -. DR ChEMBL; CHEMBL4523344; -. DR GlyGen; Q6N021; 9 sites, 1 O-linked glycan (9 sites). DR iPTMnet; Q6N021; -. DR PhosphoSitePlus; Q6N021; -. DR BioMuta; TET2; -. DR DMDM; 239938839; -. DR jPOST; Q6N021; -. DR MassIVE; Q6N021; -. DR PaxDb; 9606-ENSP00000442788; -. DR PeptideAtlas; Q6N021; -. DR ProteomicsDB; 66598; -. [Q6N021-1] DR ProteomicsDB; 66599; -. [Q6N021-2] DR ProteomicsDB; 66600; -. [Q6N021-3] DR Pumba; Q6N021; -. DR Antibodypedia; 45118; 452 antibodies from 37 providers. DR DNASU; 54790; -. DR Ensembl; ENST00000265149.9; ENSP00000265149.5; ENSG00000168769.15. [Q6N021-3] DR Ensembl; ENST00000305737.6; ENSP00000306705.2; ENSG00000168769.15. [Q6N021-2] DR Ensembl; ENST00000380013.9; ENSP00000369351.4; ENSG00000168769.15. [Q6N021-1] DR Ensembl; ENST00000540549.5; ENSP00000442788.1; ENSG00000168769.15. [Q6N021-1] DR GeneID; 54790; -. DR KEGG; hsa:54790; -. DR MANE-Select; ENST00000380013.9; ENSP00000369351.4; NM_001127208.3; NP_001120680.1. DR UCSC; uc003hxj.3; human. [Q6N021-1] DR AGR; HGNC:25941; -. DR CIViC; 54790; 8 evidence items across 3 molecular profiles. DR ClinPGx; PA162405634; -. DR CTD; 54790; -. DR DisGeNET; 54790; -. DR GeneCards; TET2; -. DR HGNC; HGNC:25941; TET2. DR HPA; ENSG00000168769; Tissue enhanced (bone). DR MalaCards; TET2; -. DR MIM; 263300; phenotype. DR MIM; 612839; gene. DR MIM; 614286; phenotype. DR MIM; 619126; phenotype. DR OpenTargets; ENSG00000168769; -. DR Orphanet; 75564; Acquired idiopathic sideroblastic anemia. DR Orphanet; 86845; Acute myeloid leukaemia with myelodysplasia-related features. DR Orphanet; 98850; Aggressive systemic mastocytosis. DR Orphanet; 664729; EBV-induced lymphoproliferative disease due to TET2 deficiency. DR Orphanet; 3318; Essential thrombocythemia. DR Orphanet; 100019; Myelodysplastic neoplasm with increased blasts type 1. DR Orphanet; 100020; Myelodysplastic neoplasm with increased blasts type 2. DR Orphanet; 98826; Myelodysplastic neoplasm with low blasts. DR Orphanet; 824; Primary myelofibrosis. DR Orphanet; 98849; Systemic mastocytosis with associated hematologic neoplasm. DR VEuPathDB; HostDB:ENSG00000168769; -. DR eggNOG; ENOG502QURD; Eukaryota. DR GeneTree; ENSGT00940000160003; -. DR HOGENOM; CLU_274735_0_0_1; -. DR InParanoid; Q6N021; -. DR OMA; HYSKPAW; -. DR OrthoDB; 8854879at2759; -. DR PAN-GO; Q6N021; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q6N021; -. DR PathwayCommons; Q6N021; -. DR Reactome; R-HSA-5221030; TET1,2,3 and TDG demethylate DNA. DR Reactome; R-HSA-9827857; Specification of primordial germ cells. DR SignaLink; Q6N021; -. DR SIGNOR; Q6N021; -. DR Agora; ENSG00000168769; -. DR BioGRID-ORCS; 54790; 8 hits in 1185 CRISPR screens. DR ChiTaRS; TET2; human. DR EvolutionaryTrace; Q6N021; -. DR GenomeRNAi; 54790; -. DR Pharos; Q6N021; Tchem. DR PRO; PR:Q6N021; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q6N021; protein. DR Bgee; ENSG00000168769; Expressed in palpebral conjunctiva and 184 other cell types or tissues. DR ExpressionAtlas; Q6N021; baseline and differential. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0070579; F:DNA 5-methylcytosine dioxygenase activity; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0002521; P:leukocyte differentiation; IMP:UniProtKB. DR GO; GO:0030099; P:myeloid cell differentiation; IMP:UniProtKB. DR GO; GO:0044029; P:positive regulation of gene expression via chromosomal CpG island demethylation; IDA:ARUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0006493; P:protein O-linked glycosylation; IDA:UniProtKB. DR CDD; cd18896; TET2; 1. DR InterPro; IPR024779; 2OGFeDO_JBP1/TET_oxygenase_dom. DR InterPro; IPR040175; TET1/2/3. DR InterPro; IPR046942; TET_oxygenase. DR PANTHER; PTHR23358; METHYLCYTOSINE DIOXYGENASE TET; 1. DR PANTHER; PTHR23358:SF3; METHYLCYTOSINE DIOXYGENASE TET2; 1. DR Pfam; PF12851; Tet_JBP; 1. DR SMART; SM01333; Tet_JBP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; KW Chromatin regulator; Chromosome; Dioxygenase; Disease variant; DNA-binding; KW Glycoprotein; Iron; Isopeptide bond; Metal-binding; Methylation; Nucleus; KW Oxidoreductase; Phosphoprotein; Proteomics identification; KW Reference proteome; Tumor suppressor; Ubl conjugation; Zinc. FT CHAIN 1..2002 FT /note="Methylcytosine dioxygenase TET2" FT /id="PRO_0000324588" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 113..154 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 266..287 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 349..368 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 390..488 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 703..748 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 930..949 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1075..1095 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1290..1303 FT /note="Interaction with DNA" FT REGION 1475..1507 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1521..1587 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1932..1961 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..11 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 113..124 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 126..143 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 267..283 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 397..416 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 479..488 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 703..718 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 731..748 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 935..944 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1081..1095 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1477..1487 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1496..1507 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1523..1532 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1539..1551 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1554..1568 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1951..1960 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1133 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1135 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1193 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1219 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1221 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1261 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1271 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1273 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1289 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1298 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1358 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1374 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1380 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1382 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1384 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1387 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1416 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1881 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1896..1898 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1902..1904 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:24315485" FT BINDING 1912 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24315485" FT MOD_RES 15 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4JK59" FT MOD_RES 75 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 99 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1107 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1109 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1682 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT CROSSLNK 1299 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25557551" FT VAR_SEQ 1137..1194 FT /note="EQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGK FT SSQGCP -> GLDRRVKLLGLKESSILVKKAKVLRDVLLLSGWFAEAAVKRSYCVWCGS FT ELATPVRLQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12880961" FT /id="VSP_032282" FT VAR_SEQ 1137..1165 FT /note="EQIIEKDEGPFYTHLGAGPNVAAIREIME -> GKCQKCTETHGVYPELANL FT SSDMGFSFFF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005" FT /id="VSP_032283" FT VAR_SEQ 1166..2002 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005" FT /id="VSP_032284" FT VAR_SEQ 1195..2002 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12880961" FT /id="VSP_032285" FT VARIANT 29 FT /note="P -> R (in dbSNP:rs12498609)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_039841" FT VARIANT 34 FT /note="L -> F (in dbSNP:rs111948941)" FT /evidence="ECO:0000269|PubMed:19420352, FT ECO:0000269|PubMed:19483684" FT /id="VAR_058171" FT VARIANT 123 FT /note="R -> H (in dbSNP:rs773565437)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058130" FT VARIANT 145 FT /note="S -> N (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs114619974)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058172" FT VARIANT 174 FT /note="P -> H (in dbSNP:rs146031219)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058173" FT VARIANT 218 FT /note="V -> M (in dbSNP:rs6843141)" FT /evidence="ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:19483684" FT /id="VAR_039842" FT VARIANT 308 FT /note="A -> T (in chronic myelomonocytic leukemia and acute FT myeloid leukemia samples; dbSNP:rs569067880)" FT /evidence="ECO:0000269|PubMed:19372255" FT /id="VAR_058131" FT VARIANT 312 FT /note="N -> S (in an acute myeloid leukemia sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058174" FT VARIANT 355 FT /note="G -> D (in dbSNP:rs61744960)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058132" FT VARIANT 363 FT /note="P -> L (in dbSNP:rs17253672)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_039843" FT VARIANT 399 FT /note="P -> L (in myelodysplastic/myeloproliferative FT disorders; a patient positive for mutation F-617 in JAK2)" FT /evidence="ECO:0000269|PubMed:19372255" FT /id="VAR_058133" FT VARIANT 429 FT /note="G -> R (in dbSNP:rs201642693)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058134" FT VARIANT 460 FT /note="S -> F (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs376570662)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058175" FT VARIANT 666 FT /note="D -> G (in a chronic myelomonocytic leukemia sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058176" FT VARIANT 817 FT /note="S -> T (in myelodysplastic/myeloproliferative FT disorders; dbSNP:rs753786455)" FT /evidence="ECO:0000269|PubMed:19372255" FT /id="VAR_058135" FT VARIANT 867 FT /note="Y -> H (in dbSNP:rs144386291)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:19420352, ECO:0000269|PubMed:19483684" FT /id="VAR_058177" FT VARIANT 912 FT /note="A -> G (in dbSNP:rs4145756)" FT /id="VAR_039844" FT VARIANT 924 FT /note="H -> R (in dbSNP:rs34485921)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058136" FT VARIANT 941 FT /note="P -> S (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs532738858)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058178" FT VARIANT 949 FT /note="H -> R (in dbSNP:rs778464072)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058137" FT VARIANT 1073 FT /note="E -> V" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058179" FT VARIANT 1084 FT /note="Q -> P (in dbSNP:rs75056899)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:19420352, ECO:0000269|PubMed:19483684" FT /id="VAR_058180" FT VARIANT 1135 FT /note="C -> Y (in a myeloproliferative disorder; somatic FT mutation; dbSNP:rs769422572)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058181" FT VARIANT 1167 FT /note="R -> T (in a myelodysplatic/myeloproliferative FT disorder and a chronic myelomonocytic leukemia sample)" FT /evidence="ECO:0000269|PubMed:19372255" FT /id="VAR_058138" FT VARIANT 1175 FT /note="I -> V (in a refractory anemia with ringed FT sideroblasts sample)" FT /evidence="ECO:0000269|PubMed:19474426" FT /id="VAR_058139" FT VARIANT 1204 FT /note="S -> C (in a myeloproliferative disorder; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058182" FT VARIANT 1214 FT /note="R -> W (in a myelodysplastic syndrome; somatic FT mutation in a chronic myelomonocytic leukemia sample; FT dbSNP:rs761811530)" FT /evidence="ECO:0000269|PubMed:19420352, FT ECO:0000269|PubMed:19483684" FT /id="VAR_058183" FT VARIANT 1237..1239 FT /note="Missing (in a polycythemia vera sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19474426" FT /id="VAR_058140" FT VARIANT 1242 FT /note="D -> R (requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:19262601" FT /id="VAR_058198" FT VARIANT 1242 FT /note="D -> V (in myeloproliferative disorders)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058184" FT VARIANT 1245 FT /note="Y -> S (in a myeloproliferative disorder; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058185" FT VARIANT 1261 FT /note="R -> C (in a myeloproliferative disorder; somatic FT mutation; dbSNP:rs898441677)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058186" FT VARIANT 1261 FT /note="R -> H (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs771761785)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058187" FT VARIANT 1261 FT /note="R -> L (in a myelodysplastic syndrome)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058141" FT VARIANT 1285 FT /note="Missing (in a myelodysplastic syndrome; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058142" FT VARIANT 1287 FT /note="F -> L (in myelodysplastic/myeloproliferative FT disorders; no effect on interaction with DCAF1, FT monoubiquitination, nor on 5-methylcytosine demethylase FT activity in vivo, when tested in a heterologous system)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:25557551" FT /id="VAR_058143" FT VARIANT 1291 FT /note="W -> R (in a myelodysplastic syndrome; somatic FT mutation; loss of 5-methylcytosine demethylase activity in FT vivo; no effect on interaction with DCAF1, nor on FT monoubiquitination, when tested in a heterologous system)" FT /evidence="ECO:0000269|PubMed:19483684, FT ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:25557551" FT /id="VAR_058144" FT VARIANT 1299 FT /note="K -> E (in a refractory anemia sample; loss of FT monoubiquitination, chromatin binding and 5-methylcytosine FT demethylase activity in vivo, when tested in a heterologous FT system)" FT /evidence="ECO:0000269|PubMed:19474426, FT ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:25557551" FT /id="VAR_058145" FT VARIANT 1299 FT /note="K -> N (in chronic myelomonocytic leukemia samples; FT loss of monoubiquitination, chromatin binding and 5- FT methylcytosine demethylase activity in vivo, when tested in FT a heterologous system)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:25557551" FT /id="VAR_058146" FT VARIANT 1302 FT /note="R -> G (in primary myelofibrosis and chronic FT myelomonocytic leukemia samples; loss of interaction with FT DCAF1, monoubiquitination and of 5-methylcytosine FT demethylase activity in vivo, when tested in a heterologous FT system)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:19474426, ECO:0000269|PubMed:25557551" FT /id="VAR_058147" FT VARIANT 1318 FT /note="E -> G (in chronic myelomonocytic leukemia samples; FT no effect on interaction with DCAF1, monoubiquitination, FT nor on 5-methylcytosine demethylase activity in vivo, when FT tested in a heterologous system)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:25557551" FT /id="VAR_058148" FT VARIANT 1367 FT /note="P -> S (in a chronic myelomonocytic leukemia FT sample)" FT /id="VAR_058149" FT VARIANT 1382 FT /note="H -> R (in IMD75; loss of methylcytosine dioxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:32518946" FT /id="VAR_085544" FT VARIANT 1396 FT /note="C -> W (in a myelodysplastic syndrome)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058150" FT VARIANT 1398 FT /note="L -> R (in a myelodysplastic syndrome; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058151" FT VARIANT 1417 FT /note="V -> F (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs749210253)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058188" FT VARIANT 1632..2002 FT /note="Missing (in IMD75; loss of protein expression; loss FT of methylcytosine dioxygenase activity)" FT /evidence="ECO:0000269|PubMed:32518946" FT /id="VAR_085545" FT VARIANT 1701 FT /note="M -> I (in dbSNP:rs62623390)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058189" FT VARIANT 1718 FT /note="V -> L (in refractory anemia with ringed FT sideroblasts; somatic mutation in an acute myeloid leukemia FT sample; dbSNP:rs142312318)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:19420352" FT /id="VAR_058190" FT VARIANT 1721 FT /note="L -> W (in dbSNP:rs34402524)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058191" FT VARIANT 1723 FT /note="P -> S (in dbSNP:rs146348065)" FT /evidence="ECO:0000269|PubMed:19420352, FT ECO:0000269|PubMed:19483684" FT /id="VAR_058192" FT VARIANT 1757 FT /note="H -> D (in a chronic myelomonocytic leukemia sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058152" FT VARIANT 1762 FT /note="I -> V (in dbSNP:rs2454206)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:19483684" FT /id="VAR_058193" FT VARIANT 1778 FT /note="H -> R (in dbSNP:rs62621450)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058194" FT VARIANT 1811 FT /note="C -> R (in a chronic myelomonocytic leukemia sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058153" FT VARIANT 1828 FT /note="Q -> L (in a myeloproliferative disorder; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058154" FT VARIANT 1869 FT /note="G -> W (in an essential thrombocythemia sample; FT dbSNP:rs1453845082)" FT /evidence="ECO:0000269|PubMed:19474426" FT /id="VAR_058155" FT VARIANT 1872 FT /note="L -> P (in a refractory anemia with excess blasts FT sample)" FT /evidence="ECO:0000269|PubMed:19474426" FT /id="VAR_058156" FT VARIANT 1873 FT /note="I -> T (in myelodysplastic syndromes, FT myeloproliferative disorders and chronic myelomonocytic FT leukemia; somatic mutation in acute myeloid leukemia and FT chronic myelomonocytic leukemia samples; FT dbSNP:rs116519313)" FT /evidence="ECO:0000269|PubMed:19262601, FT ECO:0000269|PubMed:19372255, ECO:0000269|PubMed:19420352, FT ECO:0000269|PubMed:19474426, ECO:0000269|PubMed:19483684" FT /id="VAR_058157" FT VARIANT 1875 FT /note="C -> R (in a myelodysplastic syndrome; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058195" FT VARIANT 1881 FT /note="H -> Q (in a myelodysplastic syndrome; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058196" FT VARIANT 1881 FT /note="H -> R (in a myeloproliferative disorder; somatic FT mutation; also in a patient with systemic mastocytosis FT associated with chronic myelomonocytic leukemia; FT dbSNP:rs1417392445)" FT /evidence="ECO:0000269|PubMed:19262599, FT ECO:0000269|PubMed:19420352" FT /id="VAR_058158" FT VARIANT 1896 FT /note="R -> M (in a primary acute myeloid leukemia sample; FT somatic mutation; reduces enzyme activity)" FT /evidence="ECO:0000269|PubMed:19474426, FT ECO:0000269|PubMed:24315485" FT /id="VAR_058159" FT VARIANT 1896 FT /note="R -> S (in a myeloproliferative disorder; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058197" FT VARIANT 1898 FT /note="S -> F (in a secondary acute myeloid leukemia FT sample; somatic mutation; loss of enzyme activity; FT dbSNP:rs767475870)" FT /evidence="ECO:0000269|PubMed:19474426, FT ECO:0000269|PubMed:24315485" FT /id="VAR_058160" FT VARIANT 1900 FT /note="V -> A" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058161" FT VARIANT 1911..1916 FT /note="Missing (in a myelodysplastic syndrome; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058162" FT VARIANT 1913 FT /note="G -> D (in myelodysplastic syndromes; refractory FT cytopenia with multilineage dysplasia and ringed FT sideroblasts; somatic mutation in a patient)" FT /evidence="ECO:0000269|PubMed:19372255, FT ECO:0000269|PubMed:19483684" FT /id="VAR_058163" FT VARIANT 1919 FT /note="A -> V (in a myeloproliferative disorder; somatic FT mutation; dbSNP:rs1163887807)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058164" FT VARIANT 1926 FT /note="R -> H (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs1316795626)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058165" FT VARIANT 1941 FT /note="P -> S (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs1283441077)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058166" FT VARIANT 1962 FT /note="P -> L (in a myelodysplastic syndrome; FT dbSNP:rs200971953)" FT /evidence="ECO:0000269|PubMed:19483684" FT /id="VAR_058167" FT VARIANT 1966 FT /note="R -> H (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs754215085)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058168" FT VARIANT 1974 FT /note="R -> M (in a chronic myelomonocytic leukemia sample; FT somatic mutation; dbSNP:rs1406914931)" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058169" FT VARIANT 2000 FT /note="R -> K" FT /evidence="ECO:0000269|PubMed:19420352" FT /id="VAR_058170" FT MUTAGEN 1261 FT /note="R->G: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1262 FT /note="R->A: Slightly reduces enzyme activity." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1290 FT /note="S->A: Reduces enzyme activity; when associated with FT A-1295." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1291..1296 FT /note="WSMYYN->GGSGGS: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1292 FT /note="S->R: No effect on interaction with DCAF1, FT monoubiquitination, nor on 5-methylcytosine demethylase FT activity in vivo, when tested in a heterologous system." FT /evidence="ECO:0000269|PubMed:25557551" FT MUTAGEN 1293..1294 FT /note="MY->AA: Strongly reduced enzyme activity. Slightly FT decreased affinity for DNA." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1295 FT /note="Y->A: Reduces enzyme activity; when associated with FT A-1290." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1298 FT /note="C->Y: Loss of monoubiquitination and of 5- FT methylcytosine demethylase activity in vivo. No effect on FT interaction with DCAF1, when tested in a heterologous FT system." FT /evidence="ECO:0000269|PubMed:25557551" FT MUTAGEN 1300 FT /note="F->S: Loss of interaction with DCAF1, FT monoubiquitination and of 5-methylcytosine demethylase FT activity in vivo, when tested in a heterologous system." FT /evidence="ECO:0000269|PubMed:25557551" FT MUTAGEN 1303 FT /note="S->N: Loss of enzyme activity; when associated with FT E-1299." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1382 FT /note="H->Y: Loss of enzyme activity. Still able to enhance FT histone H2B GlcNAcylation by OGT; when associated with A- FT 1384. Loss of enzyme activity; when associated with V- FT 1384." FT /evidence="ECO:0000269|PubMed:23222540, FT ECO:0000269|PubMed:24315485" FT MUTAGEN 1384 FT /note="D->A: Loss of enzyme activity. Still able to enhance FT histone H2B GlcNAcylation by OGT; when associated with Y- FT 1382." FT /evidence="ECO:0000269|PubMed:23222540, FT ECO:0000269|PubMed:24315485" FT MUTAGEN 1384 FT /note="D->V: Loss of enzyme activity; when associated with FT Y-1382." FT /evidence="ECO:0000269|PubMed:23222540, FT ECO:0000269|PubMed:24315485" FT MUTAGEN 1387 FT /note="N->A: Near loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1902 FT /note="Y->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:24315485" FT MUTAGEN 1904 FT /note="H->R: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:24315485" FT CONFLICT 599 FT /note="Q -> R (in Ref. 3; BAA90898)" FT /evidence="ECO:0000305" FT CONFLICT 702 FT /note="H -> Q (in Ref. 1; CAE45851)" FT /evidence="ECO:0000305" FT CONFLICT 878 FT /note="L -> S (in Ref. 4; BAE45750)" FT /evidence="ECO:0000305" FT STRAND 1135..1138 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1141..1144 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1153..1156 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1157..1168 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1172..1174 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1175..1182 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1197..1200 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1209..1215 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1224..1234 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1238..1255 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1262..1264 FT /evidence="ECO:0007829|PDB:5DEU" FT TURN 1278..1280 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1283..1288 FT /evidence="ECO:0007829|PDB:5DEU" FT TURN 1293..1296 FT /evidence="ECO:0007829|PDB:5DEU" FT TURN 1299..1302 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1312..1314 FT /evidence="ECO:0007829|PDB:4NM6" FT HELIX 1316..1340 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1342..1348 FT /evidence="ECO:0007829|PDB:5DEU" FT TURN 1349..1354 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1356..1358 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1362..1364 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1370..1376 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1393..1399 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1401..1403 FT /evidence="ECO:0007829|PDB:5D9Y" FT STRAND 1405..1408 FT /evidence="ECO:0007829|PDB:4NM6" FT STRAND 1416..1418 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1421..1423 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1432..1440 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1443..1446 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1451..1459 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1844..1849 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1851..1855 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1862..1864 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1871..1874 FT /evidence="ECO:0007829|PDB:5DEU" FT TURN 1876..1878 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1881..1883 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1895..1902 FT /evidence="ECO:0007829|PDB:5DEU" FT STRAND 1904..1906 FT /evidence="ECO:0007829|PDB:5D9Y" FT HELIX 1910..1913 FT /evidence="ECO:0007829|PDB:5DEU" FT HELIX 1914..1920 FT /evidence="ECO:0007829|PDB:5DEU" SQ SEQUENCE 2002 AA; 223811 MW; 6D740305EE2A8D46 CRC64; MEQDRTNHVE GNRLSPFLIP SPPICQTEPL ATKLQNGSPL PERAHPEVNG DTKWHSFKSY YGIPCMKGSQ NSRVSPDFTQ ESRGYSKCLQ NGGIKRTVSE PSLSGLLQIK KLKQDQKANG ERRNFGVSQE RNPGESSQPN VSDLSDKKES VSSVAQENAV KDFTSFSTHN CSGPENPELQ ILNEQEGKSA NYHDKNIVLL KNKAVLMPNG ATVSASSVEH THGELLEKTL SQYYPDCVSI AVQKTTSHIN AINSQATNEL SCEITHPSHT SGQINSAQTS NSELPPKPAA VVSEACDADD ADNASKLAAM LNTCSFQKPE QLQQQKSVFE ICPSPAENNI QGTTKLASGE EFCSGSSSNL QAPGGSSERY LKQNEMNGAY FKQSSVFTKD SFSATTTPPP PSQLLLSPPP PLPQVPQLPS EGKSTLNGGV LEEHHHYPNQ SNTTLLREVK IEGKPEAPPS QSPNPSTHVC SPSPMLSERP QNNCVNRNDI QTAGTMTVPL CSEKTRPMSE HLKHNPPIFG SSGELQDNCQ QLMRNKEQEI LKGRDKEQTR DLVPPTQHYL KPGWIELKAP RFHQAESHLK RNEASLPSIL QYQPNLSNQM TSKQYTGNSN MPGGLPRQAY TQKTTQLEHK SQMYQVEMNQ GQSQGTVDQH LQFQKPSHQV HFSKTDHLPK AHVQSLCGTR FHFQQRADSQ TEKLMSPVLK QHLNQQASET EPFSNSHLLQ HKPHKQAAQT QPSQSSHLPQ NQQQQQKLQI KNKEEILQTF PHPQSNNDQQ REGSFFGQTK VEECFHGENQ YSKSSEFETH NVQMGLEEVQ NINRRNSPYS QTMKSSACKI QVSCSNNTHL VSENKEQTTH PELFAGNKTQ NLHHMQYFPN NVIPKQDLLH RCFQEQEQKS QQASVLQGYK NRNQDMSGQQ AAQLAQQRYL IHNHANVFPV PDQGGSHTQT PPQKDTQKHA ALRWHLLQKQ EQQQTQQPQT ESCHSQMHRP IKVEPGCKPH ACMHTAPPEN KTWKKVTKQE NPPASCDNVQ QKSIIETMEQ HLKQFHAKSL FDHKALTLKS QKQVKVEMSG PVTVLTRQTT AAELDSHTPA LEQQTTSSEK TPTKRTAASV LNNFIESPSK LLDTPIKNLL DTPVKTQYDF PSCRCVEQII EKDEGPFYTH LGAGPNVAAI REIMEERFGQ KGKAIRIERV IYTGKEGKSS QGCPIAKWVV RRSSSEEKLL CLVRERAGHT CEAAVIVILI LVWEGIPLSL ADKLYSELTE TLRKYGTLTN RRCALNEERT CACQGLDPET CGASFSFGCS WSMYYNGCKF ARSKIPRKFK LLGDDPKEEE KLESHLQNLS TLMAPTYKKL APDAYNNQIE YEHRAPECRL GLKEGRPFSG VTACLDFCAH AHRDLHNMQN GSTLVCTLTR EDNREFGGKP EDEQLHVLPL YKVSDVDEFG SVEAQEEKKR SGAIQVLSSF RRKVRMLAEP VKTCRQRKLE AKKAAAEKLS SLENSSNKNE KEKSAPSRTK QTENASQAKQ LAELLRLSGP VMQQSQQPQP LQKQPPQPQQ QQRPQQQQPH HPQTESVNSY SASGSTNPYM RRPNPVSPYP NSSHTSDIYG STSPMNFYST SSQAAGSYLN SSNPMNPYPG LLNQNTQYPS YQCNGNLSVD NCSPYLGSYS PQSQPMDLYR YPSQDPLSKL SLPPIHTLYQ PRFGNSQSFT SKYLGYGNQN MQGDGFSSCT IRPNVHHVGK LPPYPTHEMD GHFMGATSRL PPNLSNPNMD YKNGEHHSPS HIIHNYSAAP GMFNSSLHAL HLQNKENDML SHTANGLSKM LPALNHDRTA CVQGGLHKLS DANGQEKQPL ALVQGVASGA EDNDEVWSDS EQSFLDPDIG GVAVAPTHGS ILIECAKREL HATTPLKNPN RNHPTRISLV FYQHKSMNEP KHGLALWEAK MAEKAREKEE ECEKYGPDYV PQKSHGKKVK REPAEPHETS EPTYLRFIKS LAERTMSVTT DSTVTTSPYA FTRVTGPYNR YI //