TET2_HUMAN
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 03-AUG-2022, entry version 147.
DE RecName: Full=Methylcytosine dioxygenase TET2;
DE EC=1.14.11.n2 {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.
RX PubMed=15375572; DOI=10.3892/ijo.25.4.1193;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human CXXC10 gene in silico.";
RL Int. J. Oncol. 25:1193-1199(2004).
RN [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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=2-oxoglutarate + a 5-methyl-2'-deoxycytidine in DNA + O2 = a
CC 5-hydroxymethyl-2'-deoxycytidine in DNA + CO2 + succinate;
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.n2; 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 -!- 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 and OGT. {ECO:0000269|PubMed:23222540,
CC ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24315485}.
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; P19544: WT1; NbExp=9; IntAct=EBI-310727, EBI-2320534;
CC Q6N021-1; O15294: OGT; NbExp=5; IntAct=EBI-20717492, EBI-539828;
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 -!- 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 (IMD75) [MIM:619126]: An autosomal
CC recessive immunologic disorder characterized by recurrent infections,
CC mainly viral and affecting the respiratory tract, immunodeficieny,
CC immune dysregulation, and the development of lymphoproliferative
CC disorders, including lymphoma. {ECO:0000269|PubMed:32518946}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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 ---------------------------------------------------------------------------
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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_001127208.2. [Q6N021-1]
DR RefSeq; NP_060098.3; NM_017628.4. [Q6N021-2]
DR RefSeq; XP_005263139.1; XM_005263082.2. [Q6N021-1]
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 PDBsum; 4NM6; -.
DR PDBsum; 5D9Y; -.
DR PDBsum; 5DEU; -.
DR AlphaFoldDB; Q6N021; -.
DR SMR; Q6N021; -.
DR BioGRID; 120151; 118.
DR IntAct; Q6N021; 30.
DR MINT; Q6N021; -.
DR STRING; 9606.ENSP00000442788; -.
DR BindingDB; Q6N021; -.
DR ChEMBL; CHEMBL4523344; -.
DR GlyGen; Q6N021; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6N021; -.
DR PhosphoSitePlus; Q6N021; -.
DR BioMuta; TET2; -.
DR DMDM; 239938839; -.
DR EPD; Q6N021; -.
DR jPOST; Q6N021; -.
DR MassIVE; Q6N021; -.
DR MaxQB; Q6N021; -.
DR PaxDb; Q6N021; -.
DR PeptideAtlas; Q6N021; -.
DR PRIDE; Q6N021; -.
DR ProteomicsDB; 66598; -. [Q6N021-1]
DR ProteomicsDB; 66599; -. [Q6N021-2]
DR ProteomicsDB; 66600; -. [Q6N021-3]
DR Antibodypedia; 45118; 471 antibodies from 38 providers.
DR DNASU; 54790; -.
DR Ensembl; ENST00000265149.9; ENSP00000265149.5; ENSG00000168769.14. [Q6N021-3]
DR Ensembl; ENST00000305737.6; ENSP00000306705.2; ENSG00000168769.14. [Q6N021-2]
DR Ensembl; ENST00000380013.9; ENSP00000369351.4; ENSG00000168769.14. [Q6N021-1]
DR Ensembl; ENST00000540549.5; ENSP00000442788.1; ENSG00000168769.14. [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 CTD; 54790; -.
DR DisGeNET; 54790; -.
DR GeneCards; TET2; -.
DR HGNC; HGNC:25941; TET2.
DR HPA; ENSG00000168769; Low tissue specificity.
DR MalaCards; TET2; -.
DR MIM; 263300; phenotype.
DR MIM; 612839; gene.
DR MIM; 614286; phenotype.
DR MIM; 619126; phenotype.
DR neXtProt; NX_Q6N021; -.
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; 3318; Essential thrombocythemia.
DR Orphanet; 729; Polycythemia vera.
DR Orphanet; 824; Primary myelofibrosis.
DR Orphanet; 98826; Refractory anemia.
DR Orphanet; 100019; Refractory anemia with excess blasts type 1.
DR Orphanet; 100020; Refractory anemia with excess blasts type 2.
DR Orphanet; 98849; Systemic mastocytosis with associated hematologic neoplasm.
DR PharmGKB; PA162405634; -.
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; 29059at2759; -.
DR PhylomeDB; Q6N021; -.
DR TreeFam; TF337563; -.
DR PathwayCommons; Q6N021; -.
DR Reactome; R-HSA-5221030; TET1,2,3 and TDG demethylate DNA.
DR SignaLink; Q6N021; -.
DR SIGNOR; Q6N021; -.
DR BioGRID-ORCS; 54790; 8 hits in 1095 CRISPR screens.
DR ChiTaRS; TET2; human.
DR GenomeRNAi; 54790; -.
DR Pharos; Q6N021; Tbio.
DR PRO; PR:Q6N021; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q6N021; protein.
DR Bgee; ENSG00000168769; Expressed in palpebral conjunctiva and 182 other tissues.
DR ExpressionAtlas; Q6N021; baseline and differential.
DR Genevisible; Q6N021; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
DR GO; GO:0070579; F:methylcytosine dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006211; P:5-methylcytosine catabolic process; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; IMP:UniProtKB.
DR GO; GO:0002521; P:leukocyte differentiation; IMP:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:UniProtKB.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0035511; P:oxidative DNA demethylation; IMP:UniProtKB.
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 GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR InterPro; IPR024779; 2OGFeDO_noxygenase_dom.
DR InterPro; IPR040175; TET1/2/3.
DR PANTHER; PTHR23358; PTHR23358; 1.
DR Pfam; PF12851; Tet_JBP; 1.
DR SMART; SM01333; Tet_JBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Chromatin regulator;
KW Dioxygenase; Disease variant; DNA-binding; Glycoprotein; Iron;
KW Metal-binding; Methylation; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Tumor suppressor; 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 121..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..417
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..488
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 932..946
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1484..1498
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1538..1587
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1932..1959
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 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)"
FT /evidence="ECO:0000269|PubMed:19372255"
FT /id="VAR_058143"
FT VARIANT 1291
FT /note="W -> R (in a myelodysplastic syndrome; somatic
FT mutation; abolishes enzyme activity)"
FT /evidence="ECO:0000269|PubMed:19483684,
FT ECO:0000269|PubMed:24315485"
FT /id="VAR_058144"
FT VARIANT 1299
FT /note="K -> E (in a refractory anemia sample)"
FT /evidence="ECO:0000269|PubMed:19474426,
FT ECO:0000269|PubMed:24315485"
FT /id="VAR_058145"
FT VARIANT 1299
FT /note="K -> N (in chronic myelomonocytic leukemia samples)"
FT /evidence="ECO:0000269|PubMed:19372255"
FT /id="VAR_058146"
FT VARIANT 1302
FT /note="R -> G (in primary myelofibrosis and chronic
FT myelomonocytic leukemia samples)"
FT /evidence="ECO:0000269|PubMed:19372255,
FT ECO:0000269|PubMed:19474426"
FT /id="VAR_058147"
FT VARIANT 1318
FT /note="E -> G (in chronic myelomonocytic leukemia samples)"
FT /evidence="ECO:0000269|PubMed:19372255"
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 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 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"
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
