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Database: UniProt
Entry: Q9BYW2
LinkDB: Q9BYW2
Original site: Q9BYW2 
ID   SETD2_HUMAN             Reviewed;        2564 AA.
AC   Q9BYW2; O75397; O75405; Q17RW8; Q5BKS9; Q5QGN2; Q69YI5; Q6IN64;
AC   Q6ZN53; Q6ZS25; Q8N3R0; Q8TCN0; Q9C0D1; Q9H696; Q9NZW9;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   13-FEB-2019, entry version 164.
DE   RecName: Full=Histone-lysine N-methyltransferase SETD2 {ECO:0000305};
DE            EC=2.1.1.43 {ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:27474439};
DE   AltName: Full=HIF-1;
DE   AltName: Full=Huntingtin yeast partner B {ECO:0000303|PubMed:16118227};
DE   AltName: Full=Huntingtin-interacting protein 1;
DE            Short=HIP-1;
DE   AltName: Full=Huntingtin-interacting protein B {ECO:0000303|PubMed:16118227};
DE   AltName: Full=Lysine N-methyltransferase 3A {ECO:0000303|PubMed:19332550};
DE   AltName: Full=Protein-lysine N-methyltransferase SETD2 {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426};
DE   AltName: Full=SET domain-containing protein 2 {ECO:0000303|PubMed:19332550};
DE            Short=hSET2 {ECO:0000303|PubMed:19332550};
DE   AltName: Full=p231HBP {ECO:0000303|PubMed:11461154};
GN   Name=SETD2;
GN   Synonyms=HIF1, HYPB {ECO:0000303|PubMed:16118227},
GN   KIAA1732 {ECO:0000303|PubMed:11214970},
GN   KMT3A {ECO:0000303|PubMed:19332550},
GN   SET2 {ECO:0000303|PubMed:19332550, ECO:0000303|Ref.7};
GN   ORFNames=HSPC069;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA   Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA   Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA   Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA   Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA   Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA   Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA   Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA   Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA   Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA   Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA   Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA   Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA   Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA   Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA   Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1390.
RC   TISSUE=Brain, and Cerebellum;
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 284-2564 (ISOFORM 3),
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 927-1482 (ISOFORMS 1/2/3),
RP   AND NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2228-2564 (ISOFORM 1).
RC   TISSUE=Adipose tissue;
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.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 368-2564 (ISOFORM 1), FUNCTION
RP   (MICROBIAL INFECTION), DNA-BINDING, TISSUE SPECIFICITY, AND
RP   INTERACTION WITH HTT.
RX   PubMed=11461154; DOI=10.1006/mcne.2001.1004;
RA   Rega S., Stiewe T., Chang D.-I., Pollmeier B., Esche H.,
RA   Bardenheuer W., Marquitan G., Puetzer B.M.;
RT   "Identification of the full-length huntingtin-interacting protein
RT   p231HBP/HYPB as a DNA-binding factor.";
RL   Mol. Cell. Neurosci. 18:68-79(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 388-2564 (ISOFORM 1), AND
RP   VARIANT LEU-1962.
RC   TISSUE=Cerebellum, Duodenum, and Testis;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 481-2564 (ISOFORM 1), FUNCTION,
RP   AUTOMETHYLATION, MUTAGENESIS OF ARG-1625, AND INTERACTION WITH POLR2A.
RX   PubMed=16118227; DOI=10.1074/jbc.M504012200;
RA   Sun X.-J., Wei J., Wu X.-Y., Hu M., Wang L., Wang H.-H., Zhang Q.-H.,
RA   Chen S.-J., Huang Q.-H., Chen Z.;
RT   "Identification and characterization of a novel human histone H3
RT   lysine 36 specific methyltransferase.";
RL   J. Biol. Chem. 280:35261-35271(2005).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 481-2564 (ISOFORM 2).
RA   Sun X.J., Wei J., Wu X.Y., Hu M., Wang H.H., Zhang Q.H., Huang Q.H.,
RA   Chen Z.;
RT   "Identification of a human histone H3-K36-specific methyltransferase
RT   that is orthologous to Saccharomyces cerevisiae SET2 protein.";
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 650-2564 (ISOFORM 1), AND
RP   VARIANT LEU-1962.
RC   TISSUE=Brain;
RX   PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA   Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIX.
RT   The complete sequences of 100 new cDNA clones from brain which code
RT   for large proteins in vitro.";
RL   DNA Res. 7:347-355(2000).
RN   [9]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1402-2069.
RC   TISSUE=Umbilical cord blood;
RX   PubMed=11042152; DOI=10.1101/gr.140200;
RA   Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA   Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA   Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT   "Cloning and functional analysis of cDNAs with open reading frames for
RT   300 previously undefined genes expressed in CD34+ hematopoietic
RT   stem/progenitor cells.";
RL   Genome Res. 10:1546-1560(2000).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 2378-2564, AND INTERACTION WITH HTT.
RC   TISSUE=Frontal cortex;
RX   PubMed=9700202; DOI=10.1093/hmg/7.9.1463;
RA   Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F.,
RA   MacDonald M.E.;
RT   "Huntingtin interacts with a family of WW domain proteins.";
RL   Hum. Mol. Genet. 7:1463-1474(1998).
RN   [12]
RP   INTERACTION WITH HTT.
RX   PubMed=10958656; DOI=10.1093/hmg/9.14.2175;
RA   Passani L.A., Bedford M.T., Faber P.W., McGinnis K.M., Sharp A.H.,
RA   Gusella J.F., Vonsattel J.-P., MacDonald M.E.;
RT   "Huntingtin's WW domain partners in Huntington's disease post-mortem
RT   brain fulfill genetic criteria for direct involvement in Huntington's
RT   disease pathogenesis.";
RL   Hum. Mol. Genet. 9:2175-2182(2000).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [14]
RP   INTERACTION WITH TP53.
RX   PubMed=18585004; DOI=10.1016/j.cellsig.2008.05.012;
RA   Xie P., Tian C., An L., Nie J., Lu K., Xing G., Zhang L., He F.;
RT   "Histone methyltransferase protein SETD2 interacts with p53 and
RT   selectively regulates its downstream genes.";
RL   Cell. Signal. 20:1671-1678(2008).
RN   [15]
RP   FUNCTION, AND INTERACTION WITH IWS1.
RX   PubMed=19141475; DOI=10.1101/gad.1720008;
RA   Yoh S.M., Lucas J.S., Jones K.A.;
RT   "The Iws1:Spt6:CTD complex controls cotranscriptional mRNA
RT   biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation.";
RL   Genes Dev. 22:3422-3434(2008).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1228, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA   Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT   efficient phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-323; SER-624;
RP   SER-754; SER-1228; THR-1872; SER-2080 AND SER-2082, AND IDENTIFICATION
RP   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   [18]
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.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [19]
RP   INTERACTION WITH HNRNPL.
RX   PubMed=19332550; DOI=10.1074/jbc.M808431200;
RA   Yuan W., Xie J., Long C., Erdjument-Bromage H., Ding X., Zheng Y.,
RA   Tempst P., Chen S., Zhu B., Reinberg D.;
RT   "Heterogeneous nuclear ribonucleoprotein L is a subunit of human
RT   KMT3a/Set2 complex required for H3 Lys-36 trimethylation activity in
RT   vivo.";
RL   J. Biol. Chem. 284:15701-15707(2009).
RN   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131; SER-321; SER-323;
RP   SER-708; SER-744 AND SER-754, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [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   [21]
RP   INVOLVEMENT IN RCC.
RX   PubMed=20054297; DOI=10.1038/nature08672;
RA   Dalgliesh G.L., Furge K., Greenman C., Chen L., Bignell G., Butler A.,
RA   Davies H., Edkins S., Hardy C., Latimer C., Teague J., Andrews J.,
RA   Barthorpe S., Beare D., Buck G., Campbell P.J., Forbes S., Jia M.,
RA   Jones D., Knott H., Kok C.Y., Lau K.W., Leroy C., Lin M.L.,
RA   McBride D.J., Maddison M., Maguire S., McLay K., Menzies A.,
RA   Mironenko T., Mulderrig L., Mudie L., O'Meara S., Pleasance E.,
RA   Rajasingham A., Shepherd R., Smith R., Stebbings L., Stephens P.,
RA   Tang G., Tarpey P.S., Turrell K., Dykema K.J., Khoo S.K., Petillo D.,
RA   Wondergem B., Anema J., Kahnoski R.J., Teh B.T., Stratton M.R.,
RA   Futreal P.A.;
RT   "Systematic sequencing of renal carcinoma reveals inactivation of
RT   histone modifying genes.";
RL   Nature 463:360-363(2010).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-323; SER-624
RP   AND THR-1872, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [23]
RP   FUNCTION.
RX   PubMed=21792193; DOI=10.1038/nsmb.2123;
RA   de Almeida S.F., Grosso A.R., Koch F., Fenouil R., Carvalho S.,
RA   Andrade J., Levezinho H., Gut M., Eick D., Gut I., Andrau J.C.,
RA   Ferrier P., Carmo-Fonseca M.;
RT   "Splicing enhances recruitment of methyltransferase HYPB/Setd2 and
RT   methylation of histone H3 Lys36.";
RL   Nat. Struct. Mol. Biol. 18:977-983(2011).
RN   [24]
RP   FUNCTION.
RX   PubMed=21526191; DOI=10.1371/journal.pone.0018844;
RA   Hahn M.A., Wu X., Li A.X., Hahn T., Pfeifer G.P.;
RT   "Relationship between gene body DNA methylation and intragenic H3K9me3
RT   and H3K36me3 chromatin marks.";
RL   PLoS ONE 6:E18844-E18844(2011).
RN   [25]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-323; SER-624;
RP   SER-754 AND SER-2082, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP   SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [26]
RP   INVOLVEMENT IN LLS.
RX   PubMed=23160955; DOI=10.1126/science.1227764;
RA   O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B.,
RA   Phelps I.G., Carvill G., Kumar A., Lee C., Ankenman K., Munson J.,
RA   Hiatt J.B., Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P.,
RA   Martin B.K., Borenstein E., Nickerson D.A., Mefford H.C., Doherty D.,
RA   Akey J.M., Bernier R., Eichler E.E., Shendure J.;
RT   "Multiplex targeted sequencing identifies recurrently mutated genes in
RT   autism spectrum disorders.";
RL   Science 338:1619-1622(2012).
RN   [27]
RP   FUNCTION, INVOLVEMENT IN RCC, VARIANTS RCC ASP-1733 AND PRO-1769, AND
RP   CHARACTERIZATION OF VARIANTS RCC ASP-1733 AND PRO-1769.
RX   PubMed=23622243; DOI=10.1016/j.cell.2013.03.025;
RA   Li F., Mao G., Tong D., Huang J., Gu L., Yang W., Li G.M.;
RT   "The histone mark H3K36me3 regulates human DNA mismatch repair through
RT   its interaction with MutSalpha.";
RL   Cell 153:590-600(2013).
RN   [28]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131; SER-344; SER-422;
RP   SER-532; SER-614; SER-624; THR-626; SER-744; SER-754; SER-1098;
RP   SER-1228; SER-1696; THR-1853; THR-1872; SER-1888; SER-1952; SER-2080
RP   AND SER-2082, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   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   [29]
RP   INVOLVEMENT IN RCC.
RX   PubMed=23792563; DOI=10.1038/nature12222;
RA   Creighton C.J., Morgan M., Gunaratne P.H., Wheeler D.A., Gibbs R.A.,
RA   Gordon Robertson A., Chu A., Beroukhim R., Cibulskis K.,
RA   Signoretti S., Vandin Hsin-Ta Wu F., Raphael B.J., Verhaak R.G.,
RA   Tamboli P., Torres-Garcia W., Akbani R., Weinstein J.N., Reuter V.,
RA   Hsieh J.J., Rose Brannon A., Ari Hakimi A., Jacobsen A., Ciriello G.,
RA   Reva B., Ricketts C.J., Marston Linehan W., Stuart J.M.,
RA   Kimryn Rathmell W., Shen H., Laird P.W., Muzny D., Davis C.,
RA   Morgan M., Xi L., Chang K., Kakkar N., Trevino L.R., Benton S.,
RA   Reid J.G., Morton D., Doddapaneni H., Han Y., Lewis L., Dinh H.,
RA   Kovar C., Zhu Y., Santibanez J., Wang M., Hale W., Kalra D.,
RA   Creighton C.J., Wheeler D.A., Gibbs R.A., Getz G., Cibulskis K.,
RA   Lawrence M.S., Sougnez C., Carter S.L., Sivachenko A.,
RA   Lichtenstein L., Stewart C., Voet D., Fisher S., Gabriel S.B.,
RA   Lander E., Beroukhim R., Schumacher S.E., Tabak B., Saksena G.,
RA   Onofrio R.C., Carter S.L., Cherniack A.D., Gentry J., Ardlie K.,
RA   Sougnez C., Getz G., Gabriel S.B., Meyerson M., Gordon Robertson A.,
RA   Chu A., Chun H.J., Mungall A.J., Sipahimalani P., Stoll D., Ally A.,
RA   Balasundaram M., Butterfield Y.S., Carlsen R., Carter C., Chuah E.,
RA   Coope R.J., Dhalla N., Gorski S., Guin R., Hirst C., Hirst M.,
RA   Holt R.A., Lebovitz C., Lee D., Li H.I., Mayo M., Moore R.A.,
RA   Pleasance E., Plettner P., Schein J.E., Shafiei A., Slobodan J.R.,
RA   Tam A., Thiessen N., Varhol R.J., Wye N., Zhao Y., Birol I.,
RA   Jones S.J., Marra M.A., Auman J.T., Tan D., Jones C.D., Hoadley K.A.,
RA   Mieczkowski P.A., Mose L.E., Jefferys S.R., Topal M.D., Liquori C.,
RA   Turman Y.J., Shi Y., Waring S., Buda E., Walsh J., Wu J.,
RA   Bodenheimer T., Hoyle A.P., Simons J.V., Soloway M.G., Balu S.,
RA   Parker J.S., Neil Hayes D., Perou C.M., Kucherlapati R., Park P.,
RA   Shen H., Triche T. Jr., Weisenberger D.J., Lai P.H., Bootwalla M.S.,
RA   Maglinte D.T., Mahurkar S., Berman B.P., Van Den Berg D.J., Cope L.,
RA   Baylin S.B., Laird P.W., Creighton C.J., Wheeler D.A., Getz G.,
RA   Noble M.S., Dicara D., Zhang H., Cho J., Heiman D.I., Gehlenborg N.,
RA   Voet D., Mallard W., Lin P., Frazer S., Stojanov P., Liu Y., Zhou L.,
RA   Kim J., Lawrence M.S., Chin L., Vandin F., Wu H.T., Raphael B.J.,
RA   Benz C., Yau C., Reynolds S.M., Shmulevich I., Verhaak R.G.,
RA   Torres-Garcia W., Vegesna R., Kim H., Zhang W., Cogdell D.,
RA   Jonasch E., Ding Z., Lu Y., Akbani R., Zhang N., Unruh A.K.,
RA   Casasent T.D., Wakefield C., Tsavachidou D., Chin L., Mills G.B.,
RA   Weinstein J.N., Jacobsen A., Rose Brannon A., Ciriello G., Schultz N.,
RA   Ari Hakimi A., Reva B., Antipin Y., Gao J., Cerami E., Gross B.,
RA   Arman Aksoy B., Sinha R., Weinhold N., Onur Sumer S., Taylor B.S.,
RA   Shen R., Ostrovnaya I., Hsieh J.J., Berger M.F., Ladanyi M.,
RA   Sander C., Fei S.S., Stout A., Spellman P.T., Rubin D.L., Liu T.T.,
RA   Stuart J.M., Ng S., Paull E.O., Carlin D., Goldstein T., Waltman P.,
RA   Ellrott K., Zhu J., Haussler D., Gunaratne P.H., Xiao W., Shelton C.,
RA   Gardner J., Penny R., Sherman M., Mallery D., Morris S.,
RA   Paulauskis J., Burnett K., Shelton T., Signoretti S., Kaelin W.G.,
RA   Choueiri T., Atkins M.B., Penny R., Burnett K., Mallery D., Curley E.,
RA   Tickoo S., Reuter V., Kimryn Rathmell W., Thorne L., Boice L.,
RA   Huang M., Fisher J.C., Marston Linehan W., Vocke C.D., Peterson J.,
RA   Worrell R., Merino M.J., Schmidt L.S., Tamboli P., Czerniak B.A.,
RA   Aldape K.D., Wood C.G., Boyd J., Weaver J., Iacocca M.V., Petrelli N.,
RA   Witkin G., Brown J., Czerwinski C., Huelsenbeck-Dill L., Rabeno B.,
RA   Myers J., Morrison C., Bergsten J., Eckman J., Harr J., Smith C.,
RA   Tucker K., Anne Zach L., Bshara W., Gaudioso C., Morrison C., Dhir R.,
RA   Maranchie J., Nelson J., Parwani A., Potapova O., Fedosenko K.,
RA   Cheville J.C., Houston Thompson R., Signoretti S., Kaelin W.G.,
RA   Atkins M.B., Tickoo S., Reuter V., Marston Linehan W., Vocke C.D.,
RA   Peterson J., Merino M.J., Schmidt L.S., Tamboli P., Mosquera J.M.,
RA   Rubin M.A., Blute M.L., Kimryn Rathmell W., Pihl T., Jensen M.,
RA   Sfeir R., Kahn A., Chu A., Kothiyal P., Snyder E., Pontius J.,
RA   Ayala B., Backus M., Walton J., Baboud J., Berton D., Nicholls M.,
RA   Srinivasan D., Raman R., Girshik S., Kigonya P., Alonso S.,
RA   Sanbhadti R., Barletta S., Pot D., Sheth M., Demchok J.A.,
RA   Davidsen T., Wang Z., Yang L., Tarnuzzer R.W., Zhang J., Eley G.,
RA   Ferguson M.L., Mills Shaw K.R., Guyer M.S., Ozenberger B.A.,
RA   Sofia H.J.;
RT   "Comprehensive molecular characterization of clear cell renal cell
RT   carcinoma.";
RL   Nature 499:43-49(2013).
RN   [30]
RP   FUNCTION.
RX   PubMed=23325844; DOI=10.1093/nar/gks1472;
RA   Carvalho S., Raposo A.C., Martins F.B., Grosso A.R., Sridhara S.C.,
RA   Rino J., Carmo-Fonseca M., de Almeida S.F.;
RT   "Histone methyltransferase SETD2 coordinates FACT recruitment with
RT   nucleosome dynamics during transcription.";
RL   Nucleic Acids Res. 41:2881-2893(2013).
RN   [31]
RP   FUNCTION.
RX   PubMed=24843002; DOI=10.7554/eLife.02482;
RA   Carvalho S., Vitor A.C., Sridhara S.C., Martins F.B., Raposo A.C.,
RA   Desterro J.M., Ferreira J., de Almeida S.F.;
RT   "SETD2 is required for DNA double-strand break repair and activation
RT   of the p53-mediated checkpoint.";
RL   Elife 3:E02482-E02482(2014).
RN   [32]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-614 AND
RP   THR-1853, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [33]
RP   INVOLVEMENT IN ALL, AND VARIANTS ALL ARG-2; GLY-19; ILE-267; PRO-470;
RP   ALA-499; 794-TYR--GLU-2564 DEL; PRO-1076; GLY-1093; ALA-1171;
RP   GLY-1351; GLU-1365; 1416-GLU--GLU-2564 DEL; ASN-1453; PRO-1609;
RP   MET-1663; PRO-1821; ALA-1915; VAL-1920; SER-2361 AND
RP   2546-LYS--GLU-2564 DEL.
RX   PubMed=24662245; DOI=10.1038/ncomms4469;
RA   Mar B.G., Bullinger L.B., McLean K.M., Grauman P.V., Harris M.H.,
RA   Stevenson K., Neuberg D.S., Sinha A.U., Sallan S.E., Silverman L.B.,
RA   Kung A.L., Lo Nigro L., Ebert B.L., Armstrong S.A.;
RT   "Mutations in epigenetic regulators including SETD2 are gained during
RT   relapse in paediatric acute lymphoblastic leukaemia.";
RL   Nat. Commun. 5:3469-3469(2014).
RN   [34]
RP   INVOLVEMENT IN AML, INVOLVEMENT IN ALL, VARIANTS AML 70-ARG--GLU-2564
RP   DEL; ASN-800; GLY-1397; SER-1804; TRP-2122; 2325-GLN--GLU-2564 DEL AND
RP   LEU-2505, AND VARIANTS ALL SER-226; ILE-761; ASN-1493;
RP   1496-ARG--GLU-2564 DEL; GLN-1654; 2077-ARG--GLU-2564 DEL; ALA-2214 AND
RP   2524-CYS--GLU-2564 DEL.
RX   PubMed=24509477; DOI=10.1038/ng.2894;
RA   Zhu X., He F., Zeng H., Ling S., Chen A., Wang Y., Yan X., Wei W.,
RA   Pang Y., Cheng H., Hua C., Zhang Y., Yang X., Lu X., Cao L., Hao L.,
RA   Dong L., Zou W., Wu J., Li X., Zheng S., Yan J., Zhou J., Zhang L.,
RA   Mi S., Wang X., Zhang L., Zou Y., Chen Y., Geng Z., Wang J., Zhou J.,
RA   Liu X., Wang J., Yuan W., Huang G., Cheng T., Wang Q.F.;
RT   "Identification of functional cooperative mutations of SETD2 in human
RT   acute leukemia.";
RL   Nat. Genet. 46:287-293(2014).
RN   [35]
RP   INVOLVEMENT IN LLS.
RX   PubMed=26084711; DOI=10.1007/s10803-015-2484-8;
RA   Lumish H.S., Wynn J., Devinsky O., Chung W.K.;
RT   "SETD2 mutation in a child with autism, intellectual disabilities and
RT   epilepsy.";
RL   J. Autism Dev. Disord. 45:3764-3770(2015).
RN   [36]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-637, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25755297; DOI=10.1074/mcp.O114.044792;
RA   Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA   Vertegaal A.C.;
RT   "System-wide analysis of SUMOylation dynamics in response to
RT   replication stress reveals novel small ubiquitin-like modified target
RT   proteins and acceptor lysines relevant for genome stability.";
RL   Mol. Cell. Proteomics 14:1419-1434(2015).
RN   [37]
RP   INVOLVEMENT IN RCC.
RX   PubMed=25728682; DOI=10.1038/onc.2015.24;
RA   Kanu N., Groenroos E., Martinez P., Burrell R.A., Yi Goh X.,
RA   Bartkova J., Maya-Mendoza A., Mistrik M., Rowan A.J., Patel H.,
RA   Rabinowitz A., East P., Wilson G., Santos C.R., McGranahan N.,
RA   Gulati S., Gerlinger M., Birkbak N.J., Joshi T., Alexandrov L.B.,
RA   Stratton M.R., Powles T., Matthews N., Bates P.A., Stewart A.,
RA   Szallasi Z., Larkin J., Bartek J., Swanton C.;
RT   "SETD2 loss-of-function promotes renal cancer branched evolution
RT   through replication stress and impaired DNA repair.";
RL   Oncogene 34:5699-5708(2015).
RN   [38]
RP   FUNCTION AS ALPHA-TUBULIN METHYLTRANSFERASE, CATALYTIC ACTIVITY, AND
RP   INTERACTION WITH TUBA1A.
RX   PubMed=27518565; DOI=10.1016/j.cell.2016.07.005;
RA   Park I.Y., Powell R.T., Tripathi D.N., Dere R., Ho T.H., Blasius T.L.,
RA   Chiang Y.C., Davis I.J., Fahey C.C., Hacker K.E., Verhey K.J.,
RA   Bedford M.T., Jonasch E., Rathmell W.K., Walker C.L.;
RT   "Dual chromatin and cytoskeletal remodeling by SETD2.";
RL   Cell 166:950-962(2016).
RN   [39]
RP   POSSIBLE INVOLVEMENT IN LLS, AND FUNCTION.
RX   PubMed=27317772; DOI=10.1136/jmedgenet-2015-103638;
RA   Tlemsani C., Luscan A., Leulliot N., Bieth E., Afenjar A., Baujat G.,
RA   Doco-Fenzy M., Goldenberg A., Lacombe D., Lambert L., Odent S.,
RA   Pasche J., Sigaudy S., Buffet A., Violle-Poirsier C.,
RA   Briand-Suleau A., Laurendeau I., Chin M., Saugier-Veber P., Vidaud D.,
RA   Cormier-Daire V., Vidaud M., Pasmant E., Burglen L.;
RT   "SETD2 and DNMT3A screen in the Sotos-like syndrome French cohort.";
RL   J. Med. Genet. 53:743-751(2016).
RN   [40]
RP   FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH STAT1, AND MUTAGENESIS
RP   OF ARG-1625 AND CYS-1631.
RX   PubMed=28753426; DOI=10.1016/j.cell.2017.06.042;
RA   Chen K., Liu J., Liu S., Xia M., Zhang X., Han D., Jiang Y., Wang C.,
RA   Cao X.;
RT   "Methyltransferase SETD2-mediated methylation of STAT1 is critical for
RT   interferon antiviral activity.";
RL   Cell 170:492-506(2017).
RN   [41]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-359; LYS-637 AND LYS-776,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=28112733; DOI=10.1038/nsmb.3366;
RA   Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA   Nielsen M.L.;
RT   "Site-specific mapping of the human SUMO proteome reveals co-
RT   modification with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
RN   [42]
RP   STRUCTURE BY NMR OF 2457-2564, INTERACTION WITH POLR2A, MUTAGENESIS OF
RP   ARG-2475; LYS-2476; GLN-2480; PHE-2481; VAL-2483; LYS-2506; ARG-2510;
RP   HIS-2514; GLY-2515; GLU-2528 AND GLU-2531, AND CHARACTERIZATION OF
RP   VARIANT AML LEU-2505.
RX   PubMed=16314571; DOI=10.1073/pnas.0506350102;
RA   Li M., Phatnani H.P., Guan Z., Sage H., Greenleaf A.L., Zhou P.;
RT   "Solution structure of the Set2-Rpb1 interacting domain of human Set2
RT   and its interaction with the hyperphosphorylated C-terminal domain of
RT   Rpb1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:17636-17641(2005).
RN   [43]
RP   X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 1434-1711 IN COMPLEX WITH
RP   S-ADENOSYL-L-METHIONINE OR N-PROPYL SINEFUNGIN AND ZINC, FUNCTION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, AND MUTAGENESIS OF PHE-1668; GLN-1669; ARG-1670 AND
RP   TYR-1671.
RX   PubMed=23043551; DOI=10.1021/ja307060p;
RA   Zheng W., Ibanez G., Wu H., Blum G., Zeng H., Dong A., Li F.,
RA   Hajian T., Allali-Hassani A., Amaya M.F., Siarheyeva A., Yu W.,
RA   Brown P.J., Schapira M., Vedadi M., Min J., Luo M.;
RT   "Sinefungin derivatives as inhibitors and structure probes of protein
RT   lysine methyltransferase SETD2.";
RL   J. Am. Chem. Soc. 134:18004-18014(2012).
RN   [44]
RP   X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 1434-1711 IN COMPLEX WITH
RP   S-ADENOSYL-L-HOMOCYSTEINE AND ZINC, FUNCTION, CATALYTIC ACTIVITY,
RP   DOMAIN, AND MUTAGENESIS OF PHE-1589; TYR-1604; GLU-1636; THR-1637;
RP   PHE-1668 AND TYR-1671.
RX   PubMed=27474439; DOI=10.1101/gad.284323.116;
RA   Yang S., Zheng X., Lu C., Li G.M., Allis C.D., Li H.;
RT   "Molecular basis for oncohistone H3 recognition by SETD2
RT   methyltransferase.";
RL   Genes Dev. 30:1611-1616(2016).
RN   [45]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1435-1711 IN COMPLEX WITH
RP   S-ADENOSYL-L-HOMOCYSTEINE AND ZINC, AND DOMAIN.
RX   PubMed=28256625; DOI=10.1038/srep43906;
RA   Zhang Y., Shan C.M., Wang J., Bao K., Tong L., Jia S.;
RT   "Molecular basis for the role of oncogenic histone mutations in
RT   modulating H3K36 methylation.";
RL   Sci. Rep. 7:43906-43906(2017).
RN   [46]
RP   VARIANT LLS TRP-1815.
RX   PubMed=24852293; DOI=10.1136/jmedgenet-2014-102402;
RA   Luscan A., Laurendeau I., Malan V., Francannet C., Odent S.,
RA   Giuliano F., Lacombe D., Touraine R., Vidaud M., Pasmant E.,
RA   Cormier-Daire V.;
RT   "Mutations in SETD2 cause a novel overgrowth condition.";
RL   J. Med. Genet. 51:512-517(2014).
RN   [47]
RP   VARIANT CYS-488.
RX   PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA   D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA   Sestan N., Walsh C.A.;
RT   "Targeted DNA Sequencing from Autism Spectrum Disorder Brains
RT   Implicates Multiple Genetic Mechanisms.";
RL   Neuron 88:910-917(2015).
CC   -!- FUNCTION: Histone methyltransferase that specifically
CC       trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated
CC       'Lys-36' (H3K36me2) as substrate (PubMed:16118227,
CC       PubMed:19141475, PubMed:21526191, PubMed:21792193,
CC       PubMed:23043551, PubMed:27474439). Represents the main enzyme
CC       generating H3K36me3, a specific tag for epigenetic transcriptional
CC       activation (By similarity). Plays a role in chromatin structure
CC       modulation during elongation by coordinating recruitment of the
CC       FACT complex and by interacting with hyperphosphorylated POLR2A
CC       (PubMed:23325844). Acts as a key regulator of DNA mismatch repair
CC       in G1 and early S phase by generating H3K36me3, a mark required to
CC       recruit MSH6 subunit of the MutS alpha complex: early recruitment
CC       of the MutS alpha complex to chromatin to be replicated allows a
CC       quick identification of mismatch DNA to initiate the mismatch
CC       repair reaction (PubMed:23622243). Required for DNA double-strand
CC       break repair in response to DNA damage: acts by mediating
CC       formation of H3K36me3, promoting recruitment of RAD51 and DNA
CC       repair via homologous recombination (HR) (PubMed:24843002). Acts
CC       as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an
CC       essential role in the maintenance of a heterochromatic state, by
CC       recruiting DNA methyltransferase DNMT3A (PubMed:27317772).
CC       H3K36me3 is also enhanced in intron-containing genes, suggesting
CC       that SETD2 recruitment is enhanced by splicing and that splicing
CC       is coupled to recruitment of elongating RNA polymerase
CC       (PubMed:21792193). Required during angiogenesis (By similarity).
CC       Required for endoderm development by promoting embryonic stem cell
CC       differentiation toward endoderm: acts by mediating formation of
CC       H3K36me3 in distal promoter regions of FGFR3, leading to regulate
CC       transcription initiation of FGFR3 (By similarity). In addition to
CC       histones, also mediates methylation of other proteins, such as
CC       tubulins and STAT1 (PubMed:27518565, PubMed:28753426).
CC       Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-
CC       TubK40me3); alpha-TubK40me3 is required for normal mitosis and
CC       cytokinesis and may be a specific tag in cytoskeletal remodeling
CC       (PubMed:27518565). Involved in interferon-alpha-induced antiviral
CC       defense by mediating both monomethylation of STAT1 at 'Lys-525'
CC       and catalyzing H3K36me3 on promoters of some interferon-stimulated
CC       genes (ISGs) to activate gene transcription (PubMed:28753426).
CC       {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227,
CC       ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191,
CC       ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551,
CC       ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243,
CC       ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002,
CC       ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439,
CC       ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.
CC   -!- FUNCTION: (Microbial infection) Recruited to the promoters of
CC       adenovirus 12 E1A gene in case of infection, possibly leading to
CC       regulate its expression. {ECO:0000269|PubMed:11461154}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000269|PubMed:23043551,
CC         ECO:0000269|PubMed:27474439};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC         Evidence={ECO:0000269|PubMed:28753426};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[protein] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC         N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:54192, Rhea:RHEA-COMP:9752,
CC         Rhea:RHEA-COMP:13826, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC         Evidence={ECO:0000269|PubMed:27518565};
CC   -!- ACTIVITY REGULATION: Specifically inhibited by sinefungin
CC       derivatives. N-propyl sinefungin (Pr-SNF) interacts preferentially
CC       with SETD2. {ECO:0000269|PubMed:23043551}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.21 uM for S-adenosyl-L-methionine
CC         {ECO:0000269|PubMed:23043551};
CC         KM=0.42 uM for histone H3 {ECO:0000269|PubMed:23043551};
CC         Note=Kcat is 0.14 min(-1). {ECO:0000269|PubMed:23043551};
CC   -!- SUBUNIT: Specifically interacts with hyperphosphorylated C-
CC       terminal domain (CTD) of RNA polymerase II large subunit (POLR2A):
CC       binds to CTD heptad repeats doubly phosphorylated on 'Ser-2' and
CC       'Ser-5' of each heptad (PubMed:16118227, PubMed:16314571).
CC       Interacts with HTT (PubMed:11461154, PubMed:9700202,
CC       PubMed:10958656). Interacts with IWS1 (PubMed:19141475). Interacts
CC       with p53/TP53; leading to regulate p53/TP53 target genes
CC       (PubMed:18585004). Component of a complex with HNRNPL
CC       (PubMed:19332550). Interacts with TUBA1A; the interaction is
CC       independent on alpha-tubulin acetylation on 'Lys-40'
CC       (PubMed:27518565). Interacts with STAT1 (PubMed:28753426).
CC       {ECO:0000269|PubMed:10958656, ECO:0000269|PubMed:11461154,
CC       ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:16314571,
CC       ECO:0000269|PubMed:18585004, ECO:0000269|PubMed:19141475,
CC       ECO:0000269|PubMed:19332550, ECO:0000269|PubMed:27518565,
CC       ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:9700202}.
CC   -!- INTERACTION:
CC       P42858:HTT; NbExp=4; IntAct=EBI-945869, EBI-466029;
CC       P84022:SMAD3; NbExp=2; IntAct=EBI-945869, EBI-347161;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:E9Q5F9}.
CC       Chromosome {ECO:0000250|UniProtKB:E9Q5F9}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9BYW2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9BYW2-2; Sequence=VSP_020915;
CC         Note=No experimental confirmation available.;
CC       Name=3;
CC         IsoId=Q9BYW2-3; Sequence=VSP_020914;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC       {ECO:0000269|PubMed:11461154}.
CC   -!- DOMAIN: The low charge region mediates the transcriptional
CC       activation activity. {ECO:0000269|PubMed:16118227}.
CC   -!- DOMAIN: The catalytic SET domain binds histone H3
CC       (PubMed:27474439, PubMed:28256625). It is also able to bind
CC       oncogenic histone H3 K36M/I found in a number of cancer types, in
CC       which histone H3 'Lys-36' is replaced by a Met or an Ile residue.
CC       When binding the oncogenic variant histone H3 K36M/I, the SET
CC       domain undergoes dramatic conformational change to accommodate the
CC       histone H3 peptide, leading to sequester and inhibit SETD2
CC       activity and block global H3K36 methylation (PubMed:27474439,
CC       PubMed:28256625). {ECO:0000269|PubMed:27474439,
CC       ECO:0000269|PubMed:28256625}.
CC   -!- PTM: May be automethylated. {ECO:0000269|PubMed:16118227}.
CC   -!- DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell
CC       carcinoma is a heterogeneous group of sporadic or hereditary
CC       carcinoma derived from cells of the proximal renal tubular
CC       epithelium. It is subclassified into clear cell renal carcinoma
CC       (non-papillary carcinoma), papillary renal cell carcinoma,
CC       chromophobe renal cell carcinoma, collecting duct carcinoma with
CC       medullary carcinoma of the kidney, and unclassified renal cell
CC       carcinoma. Clear cell renal cell carcinoma is the most common
CC       subtype. {ECO:0000269|PubMed:20054297,
CC       ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:23792563,
CC       ECO:0000269|PubMed:25728682}. Note=The disease may be caused by
CC       mutations affecting the gene represented in this entry. Defects of
CC       SETD2 are associated with loss of DNA methylation at non-promoter
CC       regions (PubMed:23792563). SETD2 defects lead to aberrant and
CC       reduced nucleosome compaction and chromatin association of key
CC       replication proteins, such as MCM7 and DNA polymerase delta,
CC       leading to hinder replication fork progression and prevent loading
CC       of RAD51 homologous recombination repair factor at DNA breaks
CC       (PubMed:25728682). {ECO:0000269|PubMed:23792563,
CC       ECO:0000269|PubMed:25728682}.
CC   -!- DISEASE: Luscan-Lumish syndrome (LLS) [MIM:616831]: An autosomal
CC       dominant syndrome with a variable phenotype. Clinical features
CC       include macrocephaly, distinctive facial appearance, postnatal
CC       overgrowth, various degrees of learning difficulties, autism
CC       spectrum disorder, and intellectual disability.
CC       {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24852293,
CC       ECO:0000269|PubMed:26084711, ECO:0000269|PubMed:27317772}.
CC       Note=The disease may be caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A
CC       subtype of acute leukemia, a cancer of the white blood cells. ALL
CC       is a malignant disease of bone marrow and the most common
CC       malignancy diagnosed in children. The malignant cells are lymphoid
CC       precursor cells (lymphoblasts) that are arrested in an early stage
CC       of development. The lymphoblasts replace the normal marrow
CC       elements, resulting in a marked decrease in the production of
CC       normal blood cells. Consequently, anemia, thrombocytopenia, and
CC       neutropenia occur to varying degrees. The lymphoblasts also
CC       proliferate in organs other than the marrow, particularly the
CC       liver, spleen, and lymphnodes. {ECO:0000269|PubMed:24509477,
CC       ECO:0000269|PubMed:24662245}. Note=The disease may be caused by
CC       mutations affecting distinct genetic loci, including the gene
CC       represented in this entry.
CC   -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype
CC       of acute leukemia, a cancer of the white blood cells. AML is a
CC       malignant disease of bone marrow characterized by maturational
CC       arrest of hematopoietic precursors at an early stage of
CC       development. Clonal expansion of myeloid blasts occurs in bone
CC       marrow, blood, and other tissue. Myelogenous leukemias develop
CC       from changes in cells that normally produce neutrophils,
CC       basophils, eosinophils and monocytes.
CC       {ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:24509477}.
CC       Note=The disease may be caused by mutations affecting distinct
CC       genetic loci, including the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. SET2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF29041.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};
CC       Sequence=AAH72440.1; Type=Erroneous termination; Positions=463; Note=Translated as Glu.; Evidence={ECO:0000305};
CC       Sequence=AAI17163.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAI17165.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAT77612.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAT77613.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAB15367.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAB15367.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC       Sequence=BAC87131.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=CAC28349.1; Type=Erroneous termination; Positions=385; Note=Translated as Arg.; Evidence={ECO:0000305};
CC       Sequence=CAD38601.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
DR   EMBL; AC094020; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC127430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK026125; BAB15367.1; ALT_SEQ; mRNA.
DR   EMBL; AK127782; BAC87131.1; ALT_INIT; mRNA.
DR   EMBL; AK131371; BAD18522.1; -; mRNA.
DR   EMBL; AL713692; CAD28492.1; -; mRNA.
DR   EMBL; AL831959; CAD38601.2; ALT_INIT; mRNA.
DR   EMBL; AL833394; CAH10589.1; -; mRNA.
DR   EMBL; AJ238403; CAC28349.1; ALT_SEQ; mRNA.
DR   EMBL; BC072440; AAH72440.1; ALT_SEQ; mRNA.
DR   EMBL; BC090954; AAH90954.1; -; mRNA.
DR   EMBL; BC117162; AAI17163.1; ALT_INIT; mRNA.
DR   EMBL; BC117164; AAI17165.1; ALT_INIT; mRNA.
DR   EMBL; AY576987; AAT77612.1; ALT_INIT; mRNA.
DR   EMBL; AY576988; AAT77613.1; ALT_INIT; mRNA.
DR   EMBL; AB051519; BAB21823.2; -; mRNA.
DR   EMBL; AF161554; AAF29041.1; ALT_FRAME; mRNA.
DR   EMBL; AF049103; AAC26194.1; -; mRNA.
DR   EMBL; AF049610; AAC26846.1; -; mRNA.
DR   CCDS; CCDS2749.2; -. [Q9BYW2-1]
DR   RefSeq; NP_054878.5; NM_014159.6. [Q9BYW2-1]
DR   UniGene; Hs.517941; -.
DR   PDB; 2A7O; NMR; -; A=2457-2564.
DR   PDB; 2MDC; NMR; -; A=2385-2430.
DR   PDB; 2MDI; NMR; -; A=2377-2430.
DR   PDB; 2MDJ; NMR; -; A=2377-2430.
DR   PDB; 4FMU; X-ray; 2.10 A; A=1434-1711.
DR   PDB; 4H12; X-ray; 1.99 A; A=1434-1711.
DR   PDB; 5JJY; X-ray; 2.05 A; A=1434-1711.
DR   PDB; 5JLB; X-ray; 1.50 A; A=1434-1711.
DR   PDB; 5JLE; X-ray; 2.40 A; A=1434-1711.
DR   PDB; 5LSS; X-ray; 1.79 A; A=1433-1711.
DR   PDB; 5LSX; X-ray; 2.90 A; A=1433-1711.
DR   PDB; 5LSY; X-ray; 1.62 A; A=1433-1711.
DR   PDB; 5LSZ; X-ray; 1.62 A; A=1433-1711.
DR   PDB; 5LT6; X-ray; 2.05 A; A/B=1433-1711.
DR   PDB; 5LT7; X-ray; 1.51 A; A=1433-1711.
DR   PDB; 5LT8; X-ray; 1.57 A; A=1433-1711.
DR   PDB; 5V21; X-ray; 2.42 A; A=1435-1711.
DR   PDB; 5V22; X-ray; 2.40 A; A=1435-1711.
DR   PDBsum; 2A7O; -.
DR   PDBsum; 2MDC; -.
DR   PDBsum; 2MDI; -.
DR   PDBsum; 2MDJ; -.
DR   PDBsum; 4FMU; -.
DR   PDBsum; 4H12; -.
DR   PDBsum; 5JJY; -.
DR   PDBsum; 5JLB; -.
DR   PDBsum; 5JLE; -.
DR   PDBsum; 5LSS; -.
DR   PDBsum; 5LSX; -.
DR   PDBsum; 5LSY; -.
DR   PDBsum; 5LSZ; -.
DR   PDBsum; 5LT6; -.
DR   PDBsum; 5LT7; -.
DR   PDBsum; 5LT8; -.
DR   PDBsum; 5V21; -.
DR   PDBsum; 5V22; -.
DR   ProteinModelPortal; Q9BYW2; -.
DR   SMR; Q9BYW2; -.
DR   BioGrid; 118845; 51.
DR   IntAct; Q9BYW2; 18.
DR   STRING; 9606.ENSP00000386759; -.
DR   BindingDB; Q9BYW2; -.
DR   ChEMBL; CHEMBL3108647; -.
DR   iPTMnet; Q9BYW2; -.
DR   PhosphoSitePlus; Q9BYW2; -.
DR   BioMuta; SETD2; -.
DR   DMDM; 296452963; -.
DR   OGP; Q9BYW2; -.
DR   EPD; Q9BYW2; -.
DR   jPOST; Q9BYW2; -.
DR   MaxQB; Q9BYW2; -.
DR   PaxDb; Q9BYW2; -.
DR   PeptideAtlas; Q9BYW2; -.
DR   PRIDE; Q9BYW2; -.
DR   ProteomicsDB; 79730; -.
DR   ProteomicsDB; 79731; -. [Q9BYW2-2]
DR   ProteomicsDB; 79732; -. [Q9BYW2-3]
DR   Ensembl; ENST00000409792; ENSP00000386759; ENSG00000181555. [Q9BYW2-1]
DR   GeneID; 29072; -.
DR   KEGG; hsa:29072; -.
DR   UCSC; uc003cqs.4; human. [Q9BYW2-1]
DR   CTD; 29072; -.
DR   DisGeNET; 29072; -.
DR   EuPathDB; HostDB:ENSG00000181555.19; -.
DR   GeneCards; SETD2; -.
DR   H-InvDB; HIX0021942; -.
DR   H-InvDB; HIX0163343; -.
DR   HGNC; HGNC:18420; SETD2.
DR   HPA; HPA042451; -.
DR   MalaCards; SETD2; -.
DR   MIM; 144700; phenotype.
DR   MIM; 601626; phenotype.
DR   MIM; 612778; gene.
DR   MIM; 613065; phenotype.
DR   MIM; 616831; phenotype.
DR   neXtProt; NX_Q9BYW2; -.
DR   OpenTargets; ENSG00000181555; -.
DR   Orphanet; 821; Sotos syndrome.
DR   PharmGKB; PA143485612; -.
DR   eggNOG; KOG4442; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000160086; -.
DR   HOVERGEN; HBG093939; -.
DR   InParanoid; Q9BYW2; -.
DR   KO; K11423; -.
DR   OMA; FIGHDSH; -.
DR   OrthoDB; 507784at2759; -.
DR   PhylomeDB; Q9BYW2; -.
DR   TreeFam; TF106477; -.
DR   BRENDA; 2.1.1.43; 2681.
DR   Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR   SignaLink; Q9BYW2; -.
DR   SIGNOR; Q9BYW2; -.
DR   ChiTaRS; SETD2; human.
DR   EvolutionaryTrace; Q9BYW2; -.
DR   GeneWiki; SETD2; -.
DR   GenomeRNAi; 29072; -.
DR   PRO; PR:Q9BYW2; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000181555; Expressed in 229 organ(s), highest expression level in oviduct epithelium.
DR   ExpressionAtlas; Q9BYW2; baseline and differential.
DR   Genevisible; Q9BYW2; HS.
DR   GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR   GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:UniProtKB.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR   GO; GO:0035441; P:cell migration involved in vasculogenesis; IEA:Ensembl.
DR   GO; GO:0060977; P:coronary vasculature morphogenesis; IEA:Ensembl.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR   GO; GO:0060669; P:embryonic placenta morphogenesis; IEA:Ensembl.
DR   GO; GO:0035987; P:endodermal cell differentiation; ISS:UniProtKB.
DR   GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR   GO; GO:0097676; P:histone H3-K36 dimethylation; IDA:HGNC.
DR   GO; GO:0097198; P:histone H3-K36 trimethylation; IDA:UniProtKB.
DR   GO; GO:0048332; P:mesoderm morphogenesis; IEA:Ensembl.
DR   GO; GO:1902850; P:microtubule cytoskeleton organization involved in mitosis; IDA:UniProtKB.
DR   GO; GO:0006298; P:mismatch repair; IMP:UniProtKB.
DR   GO; GO:0001763; P:morphogenesis of a branching structure; IEA:Ensembl.
DR   GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR   GO; GO:0034728; P:nucleosome organization; IMP:UniProtKB.
DR   GO; GO:0018026; P:peptidyl-lysine monomethylation; IDA:UniProtKB.
DR   GO; GO:0018023; P:peptidyl-lysine trimethylation; IDA:UniProtKB.
DR   GO; GO:0060039; P:pericardium development; IEA:Ensembl.
DR   GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR   GO; GO:0032465; P:regulation of cytokinesis; IDA:UniProtKB.
DR   GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR   GO; GO:0010793; P:regulation of mRNA export from nucleus; IMP:UniProtKB.
DR   GO; GO:1905634; P:regulation of protein localization to chromatin; IDA:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR   GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB.
DR   GO; GO:0048864; P:stem cell development; IEA:Ensembl.
DR   GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB.
DR   GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
DR   CDD; cd00201; WW; 1.
DR   Gene3D; 1.10.1740.100; -; 1.
DR   Gene3D; 1.20.930.10; -; 1.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR013257; SRI.
DR   InterPro; IPR038190; SRI_sf.
DR   InterPro; IPR035441; TFIIS/LEDGF_dom_sf.
DR   InterPro; IPR001202; WW_dom.
DR   InterPro; IPR036020; WW_dom_sf.
DR   Pfam; PF17907; AWS; 1.
DR   Pfam; PF00856; SET; 1.
DR   Pfam; PF08236; SRI; 1.
DR   Pfam; PF00397; WW; 1.
DR   SMART; SM00570; AWS; 1.
DR   SMART; SM00508; PostSET; 1.
DR   SMART; SM00317; SET; 1.
DR   SMART; SM00456; WW; 1.
DR   SUPFAM; SSF51045; SSF51045; 1.
DR   PROSITE; PS51215; AWS; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50280; SET; 1.
DR   PROSITE; PS01159; WW_DOMAIN_1; 1.
DR   PROSITE; PS50020; WW_DOMAIN_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Alternative splicing; Antiviral defense;
KW   Autism spectrum disorder; Chromatin regulator; Chromosome;
KW   Coiled coil; Complete proteome; Developmental protein;
KW   Differentiation; Disease mutation; DNA damage; DNA repair; Immunity;
KW   Innate immunity; Isopeptide bond; Mental retardation; Metal-binding;
KW   Methyltransferase; Nucleus; Phosphoprotein; Polymorphism;
KW   Reference proteome; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase; Tumor suppressor;
KW   Ubl conjugation; Zinc.
FT   CHAIN         1   2564       Histone-lysine N-methyltransferase SETD2.
FT                                /FTId=PRO_0000252367.
FT   DOMAIN     1494   1548       AWS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00562}.
FT   DOMAIN     1550   1667       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     1674   1690       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   DOMAIN     2389   2422       WW. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00224}.
FT   REGION     1418   1714       Interaction with TUBA1A.
FT                                {ECO:0000269|PubMed:27518565}.
FT   REGION     1560   1562       Inhibitor binding.
FT                                {ECO:0000269|PubMed:23043551}.
FT   REGION     1560   1562       S-adenosyl-L-methionine binding.
FT                                {ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   REGION     1603   1605       Inhibitor binding.
FT                                {ECO:0000269|PubMed:23043551}.
FT   REGION     1603   1605       S-adenosyl-L-methionine binding.
FT                                {ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   REGION     1628   1629       Inhibitor binding.
FT                                {ECO:0000269|PubMed:23043551}.
FT   REGION     1628   1629       S-adenosyl-L-methionine binding.
FT                                {ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   REGION     2137   2366       Low charge region.
FT                                {ECO:0000269|PubMed:16118227}.
FT   REGION     2457   2564       Interaction with POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   COILED     2117   2146       {ECO:0000255}.
FT   COMPBIAS    166    247       Pro-rich.
FT   COMPBIAS    385    456       Arg-rich.
FT   COMPBIAS   2149   2232       Pro-rich.
FT   COMPBIAS   2266   2365       Gln-rich.
FT   METAL      1499   1499       Zinc 1. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1501   1501       Zinc 1. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1516   1516       Zinc 1. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1516   1516       Zinc 2. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1520   1520       Zinc 1. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1529   1529       Zinc 2. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1533   1533       Zinc 2. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1539   1539       Zinc 2. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1631   1631       Zinc 3. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1678   1678       Zinc 3. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1680   1680       Zinc 3. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   METAL      1685   1685       Zinc 3. {ECO:0000244|PDB:4FMU,
FT                                ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V21,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   BINDING    1625   1625       Inhibitor. {ECO:0000269|PubMed:23043551}.
FT   BINDING    1676   1676       Inhibitor; alternate.
FT                                {ECO:0000269|PubMed:23043551}.
FT   BINDING    1676   1676       S-adenosyl-L-methionine; alternate.
FT                                {ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   BINDING    1679   1679       Inhibitor; via amide nitrogen; alternate.
FT                                {ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:28256625}.
FT   BINDING    1679   1679       S-adenosyl-L-methionine; via amide
FT                                nitrogen; alternate.
FT                                {ECO:0000244|PDB:4H12,
FT                                ECO:0000244|PDB:5JJY,
FT                                ECO:0000244|PDB:5JLB,
FT                                ECO:0000244|PDB:5JLE,
FT                                ECO:0000244|PDB:5V22,
FT                                ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439,
FT                                ECO:0000269|PubMed:28256625}.
FT   MOD_RES     131    131       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     321    321       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     323    323       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692}.
FT   MOD_RES     344    344       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     422    422       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     532    532       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     614    614       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     624    624       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     626    626       Phosphothreonine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     698    698       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES     708    708       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332}.
FT   MOD_RES     744    744       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     754    754       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1098   1098       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1228   1228       Phosphoserine.
FT                                {ECO:0000244|PubMed:18220336,
FT                                ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1413   1413       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1415   1415       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1417   1417       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1696   1696       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1844   1844       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1845   1845       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1853   1853       Phosphothreonine.
FT                                {ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES    1872   1872       Phosphothreonine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1888   1888       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1952   1952       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1980   1980       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1988   1988       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    1995   1995       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:E9Q5F9}.
FT   MOD_RES    2080   2080       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES    2082   2082       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   CROSSLNK    359    359       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   CROSSLNK    637    637       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:25755297,
FT                                ECO:0000244|PubMed:28112733}.
FT   CROSSLNK    776    776       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   VAR_SEQ    1573   2564       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_020914.
FT   VAR_SEQ    1715   2564       Missing (in isoform 2).
FT                                {ECO:0000303|Ref.7}.
FT                                /FTId=VSP_020915.
FT   VARIANT       2      2       K -> R (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079054.
FT   VARIANT      19     19       E -> G (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079055.
FT   VARIANT      70   2564       Missing (in AML; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079056.
FT   VARIANT     226    226       P -> S (in ALL; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs780963440).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079057.
FT   VARIANT     267    267       V -> I (in ALL; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs186148199).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079058.
FT   VARIANT     470    470       S -> P (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079059.
FT   VARIANT     488    488       Y -> C (found in a patient with autism;
FT                                unknown pathological significance;
FT                                dbSNP:rs757781388).
FT                                {ECO:0000269|PubMed:26637798}.
FT                                /FTId=VAR_078707.
FT   VARIANT     499    499       T -> A (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079060.
FT   VARIANT     761    761       M -> I (in ALL; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs188887061).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079061.
FT   VARIANT     768    768       V -> L (in dbSNP:rs9311404).
FT                                /FTId=VAR_027839.
FT   VARIANT     794   2564       Missing (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079062.
FT   VARIANT     800    800       S -> N (in AML; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs1169288572).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079063.
FT   VARIANT     902    902       E -> Q (in dbSNP:rs58906143).
FT                                /FTId=VAR_061216.
FT   VARIANT    1076   1076       S -> P (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079064.
FT   VARIANT    1093   1093       S -> G (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079065.
FT   VARIANT    1171   1171       T -> A (in ALL; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs540476365).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079066.
FT   VARIANT    1351   1351       D -> G (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079067.
FT   VARIANT    1365   1365       G -> E (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079068.
FT   VARIANT    1397   1397       D -> G (in AML; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs754921650).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079069.
FT   VARIANT    1416   2564       Missing (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079070.
FT   VARIANT    1453   1453       D -> N (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079071.
FT   VARIANT    1493   1493       D -> N (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079072.
FT   VARIANT    1496   2564       Missing (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079073.
FT   VARIANT    1609   1609       L -> P (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079074.
FT   VARIANT    1654   1654       K -> Q (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079075.
FT   VARIANT    1663   1663       T -> M (in ALL; unknown pathological
FT                                significance; somatic mutation;
FT                                dbSNP:rs1478147351).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079076.
FT   VARIANT    1733   1733       N -> D (in RCC; defects in recruitment of
FT                                the MutS alpha complex).
FT                                {ECO:0000269|PubMed:23622243}.
FT                                /FTId=VAR_069812.
FT   VARIANT    1769   1769       S -> P (in RCC; defects in recruitment of
FT                                the MutS alpha complex).
FT                                {ECO:0000269|PubMed:23622243}.
FT                                /FTId=VAR_069813.
FT   VARIANT    1804   1804       L -> S (in AML; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079077.
FT   VARIANT    1815   1815       L -> W (in LLS; unknown pathological
FT                                significance; dbSNP:rs869025570).
FT                                {ECO:0000269|PubMed:24852293}.
FT                                /FTId=VAR_076536.
FT   VARIANT    1821   1821       L -> P (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079078.
FT   VARIANT    1868   1868       A -> D (in dbSNP:rs11721074).
FT                                /FTId=VAR_027840.
FT   VARIANT    1915   1915       V -> A (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079079.
FT   VARIANT    1920   1920       E -> V (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079080.
FT   VARIANT    1962   1962       P -> L (in dbSNP:rs4082155).
FT                                {ECO:0000269|PubMed:11214970,
FT                                ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_027841.
FT   VARIANT    2077   2564       Missing (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079081.
FT   VARIANT    2122   2122       R -> W (in AML; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079082.
FT   VARIANT    2214   2214       T -> A (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079083.
FT   VARIANT    2325   2564       Missing (in AML; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079084.
FT   VARIANT    2361   2361       P -> S (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079085.
FT   VARIANT    2505   2505       F -> L (in AML; Impairs interaction with
FT                                hyperphosphorylated POLR2A; unknown
FT                                pathological significance; somatic
FT                                mutation). {ECO:0000269|PubMed:16314571,
FT                                ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079086.
FT   VARIANT    2524   2564       Missing (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24509477}.
FT                                /FTId=VAR_079087.
FT   VARIANT    2546   2564       Missing (in ALL; unknown pathological
FT                                significance; somatic mutation).
FT                                {ECO:0000269|PubMed:24662245}.
FT                                /FTId=VAR_079088.
FT   MUTAGEN    1589   1589       F->A: Strongly reduced methyltransferase
FT                                activity. {ECO:0000269|PubMed:27474439}.
FT   MUTAGEN    1604   1604       Y->A: Increased methyltransferase
FT                                activity. {ECO:0000269|PubMed:27474439}.
FT   MUTAGEN    1625   1625       R->H,G: Loss of methyltransferase
FT                                activity. Abolishes ability to
FT                                monomethylate STAT1.
FT                                {ECO:0000269|PubMed:16118227,
FT                                ECO:0000269|PubMed:28753426}.
FT   MUTAGEN    1631   1631       C->A: Does not affect methyltransferase
FT                                activity. {ECO:0000269|PubMed:28753426}.
FT   MUTAGEN    1636   1636       E->A: Increased methyltransferase
FT                                activity. {ECO:0000269|PubMed:27474439}.
FT   MUTAGEN    1637   1637       T->A: Increased methyltransferase
FT                                activity. {ECO:0000269|PubMed:27474439}.
FT   MUTAGEN    1668   1668       F->A: Strongly reduced methyltransferase
FT                                activity. {ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439}.
FT   MUTAGEN    1669   1669       Q->A: Loss of methyltransferase activity.
FT                                {ECO:0000269|PubMed:23043551}.
FT   MUTAGEN    1670   1670       R->A,V,L,I,F: Impaired methyltransferase
FT                                activity. {ECO:0000269|PubMed:23043551}.
FT   MUTAGEN    1670   1670       R->P,W,K,Q: Loss of methyltransferase
FT                                activity. {ECO:0000269|PubMed:23043551}.
FT   MUTAGEN    1671   1671       Y->A: Strongly reduced methyltransferase
FT                                activity. {ECO:0000269|PubMed:23043551,
FT                                ECO:0000269|PubMed:27474439}.
FT   MUTAGEN    2475   2475       R->A: Does not affect interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2476   2476       K->A: Does not affect interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2480   2480       Q->A: Does not affect interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2481   2481       F->A: Does not affect interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2483   2483       V->A: Impairs interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2506   2506       K->A: Impairs interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2510   2510       R->A: Impairs interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2514   2514       H->A: Impairs interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2515   2515       G->A,T: Does not affect interaction with
FT                                hyperphosphorylated POLR2A.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2528   2528       E->A: Increases interaction with
FT                                hyperphosphorylated POLR2A; when
FT                                associated with A-2531.
FT                                {ECO:0000269|PubMed:16314571}.
FT   MUTAGEN    2531   2531       E->A: Increases interaction with
FT                                hyperphosphorylated POLR2A; when
FT                                associated with A-2528.
FT                                {ECO:0000269|PubMed:16314571}.
FT   CONFLICT    448    448       R -> Q (in Ref. 2; BAD18522).
FT                                {ECO:0000305}.
FT   CONFLICT    455    455       A -> V (in Ref. 3; CAD38601).
FT                                {ECO:0000305}.
FT   CONFLICT    912    912       L -> P (in Ref. 2; BAB15367).
FT                                {ECO:0000305}.
FT   CONFLICT    964    964       E -> K (in Ref. 4; CAC28349, 6; AAT77612
FT                                and 7; AAT77613). {ECO:0000305}.
FT   CONFLICT   1080   1080       M -> I (in Ref. 2; BAC87131).
FT                                {ECO:0000305}.
FT   CONFLICT   1080   1080       M -> T (in Ref. 3; CAD38601).
FT                                {ECO:0000305}.
FT   CONFLICT   1212   1212       V -> F (in Ref. 2; BAD18522).
FT                                {ECO:0000305}.
FT   CONFLICT   1269   1269       T -> A (in Ref. 4; CAC28349, 6; AAT77612
FT                                and 7; AAT77613). {ECO:0000305}.
FT   CONFLICT   1338   1338       E -> G (in Ref. 2; BAB15367).
FT                                {ECO:0000305}.
FT   CONFLICT   1498   1498       Q -> R (in Ref. 3; CAD38601).
FT                                {ECO:0000305}.
FT   CONFLICT   1706   1706       K -> N (in Ref. 10; AAF29041).
FT                                {ECO:0000305}.
FT   CONFLICT   1736   1736       L -> P (in Ref. 4; CAC28349 and 6;
FT                                AAT77612). {ECO:0000305}.
FT   STRAND     1448   1450       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1451   1455       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1457   1465       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1480   1483       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1506   1511       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1521   1524       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1531   1533       {ECO:0000244|PDB:5LSX}.
FT   HELIX      1536   1538       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1539   1541       {ECO:0000244|PDB:5JLE}.
FT   TURN       1543   1547       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1552   1556       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1558   1560       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1562   1568       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1575   1578       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1582   1584       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1586   1598       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1606   1610       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1613   1616       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1618   1621       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1623   1626       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1634   1642       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1645   1654       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1661   1664       {ECO:0000244|PDB:5JLB}.
FT   HELIX      1667   1670       {ECO:0000244|PDB:5LT7}.
FT   STRAND     1672   1674       {ECO:0000244|PDB:5JLB}.
FT   STRAND     1675   1677       {ECO:0000244|PDB:5LT7}.
FT   STRAND     1687   1691       {ECO:0000244|PDB:5LT7}.
FT   HELIX      1697   1700       {ECO:0000244|PDB:5JLB}.
FT   STRAND     2377   2379       {ECO:0000244|PDB:2MDJ}.
FT   HELIX      2386   2388       {ECO:0000244|PDB:2MDI}.
FT   STRAND     2392   2399       {ECO:0000244|PDB:2MDC}.
FT   TURN       2401   2403       {ECO:0000244|PDB:2MDJ}.
FT   STRAND     2405   2409       {ECO:0000244|PDB:2MDC}.
FT   TURN       2410   2413       {ECO:0000244|PDB:2MDC}.
FT   STRAND     2414   2419       {ECO:0000244|PDB:2MDI}.
FT   STRAND     2424   2428       {ECO:0000244|PDB:2MDC}.
FT   HELIX      2463   2486       {ECO:0000244|PDB:2A7O}.
FT   TURN       2487   2489       {ECO:0000244|PDB:2A7O}.
FT   STRAND     2495   2498       {ECO:0000244|PDB:2A7O}.
FT   HELIX      2502   2524       {ECO:0000244|PDB:2A7O}.
FT   HELIX      2527   2529       {ECO:0000244|PDB:2A7O}.
FT   HELIX      2534   2548       {ECO:0000244|PDB:2A7O}.
FT   TURN       2549   2551       {ECO:0000244|PDB:2A7O}.
FT   HELIX      2557   2559       {ECO:0000244|PDB:2A7O}.
SQ   SEQUENCE   2564 AA;  287597 MW;  2B1BAE5867AB8EAB CRC64;
     MKQLQPQPPP KMGDFYDPEH PTPEEEENEA KIENVQKTGF IKGPMFKGVA SSRFLPKGTK
     TKVNLEEQGR QKVSFSFSLT KKTLQNRFLT ALGNEKQSDT PNPPAVPLQV DSTPKMKMEI
     GDTLSTAEES SPPKSRVELG KIHFKKHLLH VTSRPLLATT TAVASPPTHA APLPAVIAES
     TTVDSPPSSP PPPPPPAQAT TLSSPAPVTE PVALPHTPIT VLMAAPVPLP VDVAVRSLKE
     PPIIIVPESL EADTKQDTIS NSLEEHVTQI LNEQADISSK KEDSHIGKDE EIPDSSKISL
     SCKKTGSKKK SSQSEGIFLG SESDEDSVRT SSSQRSHDLK FSASIEKERD FKKSSAPLKS
     EDLGKPSRSK TDRDDKYFSY SKLERDTRYV SSRCRSERER RRSRSHSRSE RGSRTNLSYS
     RSERSHYYDS DRRYHRSSPY RERTRYSRPY TDNRARESSD SEEEYKKTYS RRTSSHSSSY
     RDLRTSSYSK SDRDCKTETS YLEMERRGKY SSKLERESKR TSENEAIKRC CSPPNELGFR
     RGSSYSKHDS SASRYKSTLS KPIPKSDKFK NSFCCTELNE EIKQSHSFSL QTPCSKGSEL
     RMINKNPERE KAGSPAPSNR LNDSPTLKKL DELPIFKSEF ITHDSHDSIK ELDSLSKVKN
     DQLRSFCPIE LNINGSPGAE SDLATFCTSK TDAVLMTSDD SVTGSELSPL VKACMLSSNG
     FQNISRCKEK DLDDTCMLHK KSESPFRETE PLVSPHQDKL MSMPVMTVDY SKTVVKEPVD
     TRVSCCKTKD SDIYCTLNDS NPSLCNSEAE NIEPSVMKIS SNSFMNVHLE SKPVICDSRN
     LTDHSKFACE EYKQSIGSTS SASVNHFDDL YQPIGSSGIA SSLQSLPPGI KVDSLTLLKC
     GENTSPVLDA VLKSKKSSEF LKHAGKETIV EVGSDLPDSG KGFASRENRR NNGLSGKCLQ
     EAQEEGNSIL PERRGRPEIS LDERGEGGHV HTSDDSEVVF SSCDLNLTME DSDGVTYALK
     CDSSGHAPEI VSTVHEDYSG SSESSNDESD SEDTDSDDSS IPRNRLQSVV VVPKNSTLPM
     EETSPCSSRS SQSYRHYSDH WEDERLESRR HLYEEKFESI ASKACPQTDK FFLHKGTEKN
     PEISFTQSSR KQIDNRLPEL SHPQSDGVDS TSHTDVKSDP LGHPNSEETV KAKIPSRQQE
     ELPIYSSDFE DVPNKSWQQT TFQNRPDSRL GKTELSFSSS CEIPHVDGLH SSEELRNLGW
     DFSQEKPSTT YQQPDSSYGA CGGHKYQQNA EQYGGTRDYW QGNGYWDPRS GRPPGTGVVY
     DRTQGQVPDS LTDDREEEEN WDQQDGSHFS DQSDKFLLSL QKDKGSVQAP EISSNSIKDT
     LAVNEKKDFS KNLEKNDIKD RGPLKKRRQE IESDSESDGE LQDRKKVRVE VEQGETSVPP
     GSALVGPSCV MDDFRDPQRW KECAKQGKMP CYFDLIEENV YLTERKKNKS HRDIKRMQCE
     CTPLSKDERA QGEIACGEDC LNRLLMIECS SRCPNGDYCS NRRFQRKQHA DVEVILTEKK
     GWGLRAAKDL PSNTFVLEYC GEVLDHKEFK ARVKEYARNK NIHYYFMALK NDEIIDATQK
     GNCSRFMNHS CEPNCETQKW TVNGQLRVGF FTTKLVPSGS ELTFDYQFQR YGKEAQKCFC
     GSANCRGYLG GENRVSIRAA GGKMKKERSR KKDSVDGELE ALMENGEGLS DKNQVLSLSR
     LMVRIETLEQ KLTCLELIQN THSQSCLKSF LERHGLSLLW IWMAELGDGR ESNQKLQEEI
     IKTLEHLPIP TKNMLEESKV LPIIQRWSQT KTAVPPLSEG DGYSSENTSR AHTPLNTPDP
     STKLSTEADT DTPKKLMFRR LKIISENSMD SAISDATSEL EGKDGKEDLD QLENVPVEEE
     EELQSQQLLP QQLPECKVDS ETNIEASKLP TSEPEADAEI EPKESNGTKL EEPINEETPS
     QDEEEGVSDV ESERSQEQPD KTVDISDLAT KLLDSWKDLK EVYRIPKKSQ TEKENTTTER
     GRDAVGFRDQ TPAPKTPNRS RERDPDKQTQ NKEKRKRRSS LSPPSSAYER GTKRPDDRYD
     TPTSKKKVRI KDRNKLSTEE RRKLFEQEVA QREAQKQQQQ MQNLGMTSPL PYDSLGYNAP
     HHPFAGYPPG YPMQAYVDPS NPNAGKVLLP TPSMDPVCSP APYDHAQPLV GHSTEPLSAP
     PPVPVVPHVA APVEVSSSQY VAQSDGVVHQ DSSVAVLPVP APGPVQGQNY SVWDSNQQSV
     SVQQQYSPAQ SQATIYYQGQ TCPTVYGVTS PYSQTTPPIV QSYAQPSLQY IQGQQIFTAH
     PQGVVVQPAA AVTTIVAPGQ PQPLQPSEMV VTNNLLDLPP PSPPKPKTIV LPPNWKTARD
     PEGKIYYYHV ITRQTQWDPP TWESPGDDAS LEHEAEMDLG TPTYDENPMK ASKKPKTAEA
     DTSSELAKKS KEVFRKEMSQ FIVQCLNPYR KPDCKVGRIT TTEDFKHLAR KLTHGVMNKE
     LKYCKNPEDL ECNENVKHKT KEYIKKYMQK FGAVYKPKED TELE
//
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