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Database: UniProt
Entry: Q6N021
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Original site: Q6N021 
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   29-SEP-2021, entry version 144.
DE   RecName: Full=Methylcytosine dioxygenase TET2;
DE            EC=1.14.11.n2 {ECO:0000269|PubMed:24315485};
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).
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   -!- 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   -!- 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   -!- 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   SMR; Q6N021; -.
DR   BioGRID; 120151; 100.
DR   IntAct; Q6N021; 19.
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; 457 antibodies.
DR   DNASU; 54790; -.
DR   Ensembl; ENST00000265149; ENSP00000265149; ENSG00000168769. [Q6N021-3]
DR   Ensembl; ENST00000305737; ENSP00000306705; ENSG00000168769. [Q6N021-2]
DR   Ensembl; ENST00000380013; ENSP00000369351; ENSG00000168769. [Q6N021-1]
DR   Ensembl; ENST00000540549; ENSP00000442788; ENSG00000168769. [Q6N021-1]
DR   GeneID; 54790; -.
DR   KEGG; hsa:54790; -.
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   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; 86839; Refractory anemia with excess blasts.
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; NMQGDAF; -.
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   SIGNOR; Q6N021; -.
DR   BioGRID-ORCS; 54790; 6 hits in 1024 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 blood and 209 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:0080111; P:DNA demethylation; IDA:UniProtKB.
DR   GO; GO:0080182; P:histone H3-K4 trimethylation; 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: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; DNA-binding; Glycoprotein; Iron; Metal-binding; Methylation;
KW   Oxidoreductase; Phosphoprotein; 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          1896..1898
FT                   /note="2-oxoglutarate binding"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   REGION          1902..1904
FT                   /note="Substrate binding"
FT                   /evidence="ECO:0000269|PubMed:24315485"
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   METAL           1133
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1135
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1193
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1219
FT                   /note="Zinc 1; via pros nitrogen"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1221
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1271
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1273
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1289
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1298
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1358
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1380
FT                   /note="Zinc 2; via tele nitrogen"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1382
FT                   /note="Iron; catalytic"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1384
FT                   /note="Iron; catalytic"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1881
FT                   /note="Iron; catalytic"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   METAL           1912
FT                   /note="Zinc 3; via pros nitrogen"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   BINDING         1261
FT                   /note="2-oxoglutarate"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   BINDING         1374
FT                   /note="2-oxoglutarate"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   BINDING         1387
FT                   /note="Substrate"
FT                   /evidence="ECO:0000269|PubMed:24315485"
FT   BINDING         1416
FT                   /note="2-oxoglutarate"
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         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         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"
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
//
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