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Database: UniProt/SWISS-PROT
Entry: SETD2_HUMAN
LinkDB: SETD2_HUMAN
Original site: SETD2_HUMAN 
ID   SETD2_HUMAN             Reviewed;        2564 AA.
AC   Q9BYW2; O75397; O75405; Q17RW8; Q5BKS9; Q5QGN2; Q69YI5; Q6IN64; Q6ZN53;
AC   Q6ZS25; Q8N3R0; Q8TCN0; Q9C0D1; Q9H696; Q9NZW9;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   24-JAN-2024, entry version 191.
DE   RecName: Full=Histone-lysine N-methyltransferase SETD2 {ECO:0000305};
DE            EC=2.1.1.359 {ECO:0000269|PubMed:19332550, 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}, SET2 {ECO:0000303|PubMed:19332550,
GN   ECO:0000303|Ref.7}; ORFNames=HSPC069;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., 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., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., 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., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 284-2564 (ISOFORM 3), NUCLEOTIDE
RP   SEQUENCE [LARGE SCALE MRNA] OF 927-1482 (ISOFORMS 1/2/3), AND NUCLEOTIDE
RP   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., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 368-2564 (ISOFORM 1), FUNCTION (MICROBIAL
RP   INFECTION), DNA-BINDING, TISSUE SPECIFICITY, AND INTERACTION WITH HTT.
RX   PubMed=11461154; DOI=10.1006/mcne.2001.1004;
RA   Rega S., Stiewe T., Chang D.-I., Pollmeier B., Esche H., Bardenheuer W.,
RA   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 VARIANT
RP   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 project:
RT   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 lysine 36
RT   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 that
RT   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 VARIANT
RP   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. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   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 300
RT   previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT   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 brain
RT   fulfill genetic criteria for direct involvement in Huntington's disease
RT   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., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   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 selectively
RT   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 biosynthesis and
RT   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 BY
RP   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., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   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 BY
RP   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., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [19]
RP   FUNCTION, CATALYTIC ACTIVITY, AND 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 KMT3a/Set2
RT   complex required for H3 Lys-36 trimethylation activity in 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., McBride D.J.,
RA   Maddison M., Maguire S., McLay K., Menzies A., Mironenko T., Mulderrig L.,
RA   Mudie L., O'Meara S., Pleasance E., Rajasingham A., Shepherd R., Smith R.,
RA   Stebbings L., Stephens P., Tang G., Tarpey P.S., Turrell K., Dykema K.J.,
RA   Khoo S.K., Petillo D., Wondergem B., Anema J., Kahnoski R.J., Teh B.T.,
RA   Stratton M.R., Futreal P.A.;
RT   "Systematic sequencing of renal carcinoma reveals inactivation of histone
RT   modifying genes.";
RL   Nature 463:360-363(2010).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-323; SER-624 AND
RP   THR-1872, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   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., Andrade J.,
RA   Levezinho H., Gut M., Eick D., Gut I., Andrau J.C., Ferrier P.,
RA   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 and
RT   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 SCALE
RP   ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   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., Phelps I.G.,
RA   Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B.,
RA   Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K.,
RA   Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M.,
RA   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 its
RT   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; SER-1228;
RP   SER-1696; THR-1853; THR-1872; SER-1888; SER-1952; SER-2080 AND SER-2082,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [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., Signoretti S.,
RA   Vandin Hsin-Ta Wu F., Raphael B.J., Verhaak R.G., Tamboli P.,
RA   Torres-Garcia W., Akbani R., Weinstein J.N., Reuter V., Hsieh J.J.,
RA   Rose Brannon A., Ari Hakimi A., Jacobsen A., Ciriello G., Reva B.,
RA   Ricketts C.J., Marston Linehan W., Stuart J.M., Kimryn Rathmell W.,
RA   Shen H., Laird P.W., Muzny D., Davis C., Morgan M., Xi L., Chang K.,
RA   Kakkar N., Trevino L.R., Benton S., Reid J.G., Morton D., Doddapaneni H.,
RA   Han Y., Lewis L., Dinh H., Kovar C., Zhu Y., Santibanez J., Wang M.,
RA   Hale W., Kalra D., Creighton C.J., Wheeler D.A., Gibbs R.A., Getz G.,
RA   Cibulskis K., Lawrence M.S., Sougnez C., Carter S.L., Sivachenko A.,
RA   Lichtenstein L., Stewart C., Voet D., Fisher S., Gabriel S.B., Lander E.,
RA   Beroukhim R., Schumacher S.E., Tabak B., Saksena G., Onofrio R.C.,
RA   Carter S.L., Cherniack A.D., Gentry J., Ardlie K., Sougnez C., Getz G.,
RA   Gabriel S.B., Meyerson M., Gordon Robertson A., Chu A., Chun H.J.,
RA   Mungall A.J., Sipahimalani P., Stoll D., Ally A., Balasundaram M.,
RA   Butterfield Y.S., Carlsen R., Carter C., Chuah E., Coope R.J., Dhalla N.,
RA   Gorski S., Guin R., Hirst C., Hirst M., Holt R.A., Lebovitz C., Lee D.,
RA   Li H.I., Mayo M., Moore R.A., Pleasance E., Plettner P., Schein J.E.,
RA   Shafiei A., Slobodan J.R., Tam A., Thiessen N., Varhol R.J., Wye N.,
RA   Zhao Y., Birol I., Jones S.J., Marra M.A., Auman J.T., Tan D., Jones C.D.,
RA   Hoadley K.A., Mieczkowski P.A., Mose L.E., Jefferys S.R., Topal M.D.,
RA   Liquori C., 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., Shen H.,
RA   Triche T. Jr., Weisenberger D.J., Lai P.H., Bootwalla M.S., Maglinte D.T.,
RA   Mahurkar S., Berman B.P., Van Den Berg D.J., Cope L., Baylin S.B.,
RA   Laird P.W., Creighton C.J., Wheeler D.A., Getz G., Noble M.S., Dicara D.,
RA   Zhang H., Cho J., Heiman D.I., Gehlenborg N., Voet D., Mallard W., Lin P.,
RA   Frazer S., Stojanov P., Liu Y., Zhou L., Kim J., Lawrence M.S., Chin L.,
RA   Vandin F., Wu H.T., Raphael B.J., Benz C., Yau C., Reynolds S.M.,
RA   Shmulevich I., Verhaak R.G., Torres-Garcia W., Vegesna R., Kim H.,
RA   Zhang W., Cogdell D., Jonasch E., Ding Z., Lu Y., Akbani R., Zhang N.,
RA   Unruh A.K., Casasent T.D., Wakefield C., Tsavachidou D., Chin L.,
RA   Mills G.B., Weinstein J.N., Jacobsen A., Rose Brannon A., Ciriello G.,
RA   Schultz N., Ari Hakimi A., Reva B., Antipin Y., Gao J., Cerami E.,
RA   Gross B., Arman Aksoy B., Sinha R., Weinhold N., Onur Sumer S.,
RA   Taylor B.S., 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., Paulauskis J.,
RA   Burnett K., Shelton T., Signoretti S., Kaelin W.G., Choueiri T.,
RA   Atkins M.B., Penny R., Burnett K., Mallery D., Curley E., Tickoo S.,
RA   Reuter V., Kimryn Rathmell W., Thorne L., Boice L., Huang M., Fisher J.C.,
RA   Marston Linehan W., Vocke C.D., Peterson J., Worrell R., Merino M.J.,
RA   Schmidt L.S., Tamboli P., Czerniak B.A., Aldape K.D., Wood C.G., Boyd J.,
RA   Weaver J., Iacocca M.V., Petrelli N., Witkin G., Brown J., Czerwinski C.,
RA   Huelsenbeck-Dill L., Rabeno B., Myers J., Morrison C., Bergsten J.,
RA   Eckman J., Harr J., Smith C., Tucker K., Anne Zach L., Bshara W.,
RA   Gaudioso C., Morrison C., Dhir R., Maranchie J., Nelson J., Parwani A.,
RA   Potapova O., Fedosenko K., Cheville J.C., Houston Thompson R.,
RA   Signoretti S., Kaelin W.G., Atkins M.B., Tickoo S., Reuter V.,
RA   Marston Linehan W., Vocke C.D., Peterson J., Merino M.J., Schmidt L.S.,
RA   Tamboli P., Mosquera J.M., Rubin M.A., Blute M.L., Kimryn Rathmell W.,
RA   Pihl T., Jensen M., Sfeir R., Kahn A., Chu A., Kothiyal P., Snyder E.,
RA   Pontius J., Ayala B., Backus M., Walton J., Baboud J., Berton D.,
RA   Nicholls M., Srinivasan D., Raman R., Girshik S., Kigonya P., Alonso S.,
RA   Sanbhadti R., Barletta S., Pot D., Sheth M., Demchok J.A., Davidsen T.,
RA   Wang Z., Yang L., Tarnuzzer R.W., Zhang J., Eley G., Ferguson M.L.,
RA   Mills Shaw K.R., Guyer M.S., Ozenberger B.A., 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 of the
RT   p53-mediated checkpoint.";
RL   Elife 3:E02482-E02482(2014).
RN   [32]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-614 AND THR-1853,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [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; GLY-1351;
RP   GLU-1365; 1416-GLU--GLU-2564 DEL; ASN-1453; PRO-1609; MET-1663; PRO-1821;
RP   ALA-1915; VAL-1920; SER-2361 AND 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 DEL;
RP   ASN-800; GLY-1397; SER-1804; TRP-2122; 2325-GLN--GLU-2564 DEL AND LEU-2505,
RP   AND VARIANTS ALL SER-226; ILE-761; ASN-1493; 1496-ARG--GLU-2564 DEL;
RP   GLN-1654; 2077-ARG--GLU-2564 DEL; ALA-2214 AND 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., Pang Y.,
RA   Cheng H., Hua C., Zhang Y., Yang X., Lu X., Cao L., Hao L., Dong L.,
RA   Zou W., Wu J., Li X., Zheng S., Yan J., Zhou J., Zhang L., Mi S., Wang X.,
RA   Zhang L., Zou Y., Chen Y., Geng Z., Wang J., Zhou J., Liu X., Wang J.,
RA   Yuan W., Huang G., Cheng T., Wang Q.F.;
RT   "Identification of functional cooperative mutations of SETD2 in human acute
RT   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 MASS
RP   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 replication
RT   stress reveals novel small ubiquitin-like modified target proteins and
RT   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., Bartkova J.,
RA   Maya-Mendoza A., Mistrik M., Rowan A.J., Patel H., Rabinowitz A., East P.,
RA   Wilson G., Santos C.R., McGranahan N., Gulati S., Gerlinger M.,
RA   Birkbak N.J., Joshi T., Alexandrov L.B., Stratton M.R., Powles T.,
RA   Matthews N., Bates P.A., Stewart A., Szallasi Z., Larkin J., Bartek J.,
RA   Swanton C.;
RT   "SETD2 loss-of-function promotes renal cancer branched evolution through
RT   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., Pasche J.,
RA   Sigaudy S., Buffet A., Violle-Poirsier C., Briand-Suleau A., Laurendeau I.,
RA   Chin M., Saugier-Veber P., Vidaud D., Cormier-Daire V., Vidaud M.,
RA   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 OF
RP   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, AND
RP   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-modification
RT   with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
RN   [42]
RP   INTERACTION WITH HNRNPL.
RX   PubMed=36537238; DOI=10.1093/nar/gkac1134;
RA   Kerschbamer E., Arnoldi M., Tripathi T., Pellegrini M., Maturi S.,
RA   Erdin S., Salviato E., Di Leva F., Sebestyen E., Dassi E., Zarantonello G.,
RA   Benelli M., Campos E., Basson M.A., Gusella J.F., Gustincich S., Piazza S.,
RA   Demichelis F., Talkowski M.E., Ferrari F., Biagioli M.;
RT   "CHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters
RT   RNA alternative splicing.";
RL   Nucleic Acids Res. 50:12809-12828(2022).
RN   [43]
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 VARIANT
RP   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 and
RT   its interaction with the hyperphosphorylated C-terminal domain of Rpb1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:17636-17641(2005).
RN   [44] {ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12}
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 REGULATION, AND
RP   MUTAGENESIS OF PHE-1668; GLN-1669; ARG-1670 AND TYR-1671.
RX   PubMed=23043551; DOI=10.1021/ja307060p;
RA   Zheng W., Ibanez G., Wu H., Blum G., Zeng H., Dong A., Li F., Hajian T.,
RA   Allali-Hassani A., Amaya M.F., Siarheyeva A., Yu W., Brown P.J.,
RA   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   [45]
RP   X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 1434-1711 IN COMPLEX WITH
RP   S-ADENOSYL-L-HOMOCYSTEINE AND ZINC, FUNCTION, CATALYTIC ACTIVITY, DOMAIN,
RP   AND MUTAGENESIS OF PHE-1589; TYR-1604; GLU-1636; THR-1637; PHE-1668 AND
RP   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   [46]
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 modulating
RT   H3K36 methylation.";
RL   Sci. Rep. 7:43906-43906(2017).
RN   [47]
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., Giuliano F.,
RA   Lacombe D., Touraine R., Vidaud M., Pasmant E., Cormier-Daire V.;
RT   "Mutations in SETD2 cause a novel overgrowth condition.";
RL   J. Med. Genet. 51:512-517(2014).
RN   [48]
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 Implicates
RT   Multiple Genetic Mechanisms.";
RL   Neuron 88:910-917(2015).
RN   [49]
RP   VARIANT RAPAS TRP-1740, VARIANT MRD70 GLN-1740, AND INVOLVEMENT IN RAPAS
RP   AND MRD70.
RX   PubMed=32710489; DOI=10.1002/ajmg.a.61724;
RA   Rabin R., Radmanesh A., Glass I.A., Dobyns W.B., Aldinger K.A., Shieh J.T.,
RA   Romoser S., Bombei H., Dowsett L., Trapane P., Bernat J.A., Baker J.,
RA   Mendelsohn N.J., Popp B., Siekmeyer M., Sorge I., Sansbury F.H., Watts P.,
RA   Foulds N.C., Burton J., Hoganson G., Hurst J.A., Menzies L., Osio D.,
RA   Kerecuk L., Cobben J.M., Jizi K., Jacquemont S., Belanger S.A., Loehner K.,
RA   Veenstra-Knol H.E., Lemmink H.H., Keller-Ramey J., Wentzensen I.M.,
RA   Punj S., McWalter K., Lenberg J., Ellsworth K.A., Radtke K., Akbarian S.,
RA   Pappas J.;
RT   "Genotype-phenotype correlation at codon 1740 of SETD2.";
RL   Am. J. Med. Genet. A 182:2037-2048(2020).
CC   -!- FUNCTION: Histone methyltransferase that specifically trimethylates
CC       'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36'
CC       (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475,
CC       PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It
CC       is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro
CC       (PubMed:19332550). Represents the main enzyme generating H3K36me3, a
CC       specific tag for epigenetic transcriptional activation (By similarity).
CC       Plays a role in chromatin structure modulation during elongation by
CC       coordinating recruitment of the FACT complex and by interacting with
CC       hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator
CC       of DNA mismatch repair in G1 and early S phase by generating H3K36me3,
CC       a mark required to recruit MSH6 subunit of the MutS alpha complex:
CC       early recruitment of the MutS alpha complex to chromatin to be
CC       replicated allows a quick identification of mismatch DNA to initiate
CC       the mismatch repair reaction (PubMed:23622243). Required for DNA
CC       double-strand break repair in response to DNA damage: acts by mediating
CC       formation of H3K36me3, promoting recruitment of RAD51 and DNA repair
CC       via homologous recombination (HR) (PubMed:24843002). Acts as a tumor
CC       suppressor (PubMed:24509477). H3K36me3 also plays an essential role in
CC       the maintenance of a heterochromatic state, by recruiting DNA
CC       methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced
CC       in intron-containing genes, suggesting that SETD2 recruitment is
CC       enhanced by splicing and that splicing is coupled to recruitment of
CC       elongating RNA polymerase (PubMed:21792193). Required during
CC       angiogenesis (By similarity). Required for endoderm development by
CC       promoting embryonic stem cell differentiation toward endoderm: acts by
CC       mediating formation of H3K36me3 in distal promoter regions of FGFR3,
CC       leading to regulate transcription initiation of FGFR3 (By similarity).
CC       In addition to histones, also mediates methylation of other proteins,
CC       such as 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' and
CC       catalyzing H3K36me3 on promoters of some interferon-stimulated genes
CC       (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(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC         + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:60324, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC         COMP:15536, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.359;
CC         Evidence={ECO:0000269|PubMed:19332550, ECO:0000269|PubMed:23043551,
CC         ECO:0000269|PubMed:27474439};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-
CC         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:23043551, 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, Rhea:RHEA-
CC         COMP:13826, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC         Evidence={ECO:0000269|PubMed:27518565};
CC   -!- ACTIVITY REGULATION: Specifically inhibited by sinefungin derivatives.
CC       N-propyl sinefungin (Pr-SNF) interacts preferentially with SETD2.
CC       {ECO:0000269|PubMed:23043551}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.21 uM for S-adenosyl-L-methionine {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-terminal
CC       domain (CTD) of RNA polymerase II large subunit (POLR2A): binds to CTD
CC       heptad repeats doubly phosphorylated on 'Ser-2' and 'Ser-5' of each
CC       heptad (PubMed:16118227, PubMed:16314571). Interacts with HTT
CC       (PubMed:11461154, PubMed:9700202, PubMed:10958656). Interacts with IWS1
CC       (PubMed:19141475). Interacts with p53/TP53; leading to regulate
CC       p53/TP53 target genes (PubMed:18585004). Component of a complex with
CC       HNRNPL (PubMed:19332550, PubMed:36537238). Interacts with TUBA1A; the
CC       interaction is 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       Q9BYW2; P42858: HTT; NbExp=4; IntAct=EBI-945869, EBI-466029;
CC       Q9BYW2; 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       Name=3;
CC         IsoId=Q9BYW2-3; Sequence=VSP_020914;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC       {ECO:0000269|PubMed:11461154}.
CC   -!- DOMAIN: The low charge region mediates the transcriptional activation
CC       activity. {ECO:0000269|PubMed:16118227}.
CC   -!- DOMAIN: The catalytic SET domain binds histone H3 (PubMed:27474439,
CC       PubMed:28256625). It is also able to bind oncogenic histone H3 K36M/I
CC       found in a number of cancer types, in which histone H3 'Lys-36' is
CC       replaced by a Met or an Ile residue. When binding the oncogenic variant
CC       histone H3 K36M/I, the SET domain undergoes dramatic conformational
CC       change to accommodate the histone H3 peptide, leading to sequester and
CC       inhibit SETD2 activity and block global H3K36 methylation
CC       (PubMed:27474439, 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 carcinoma
CC       is a heterogeneous group of sporadic or hereditary carcinoma derived
CC       from cells of the proximal renal tubular epithelium. It is
CC       subclassified into clear cell renal carcinoma (non-papillary
CC       carcinoma), papillary renal cell carcinoma, chromophobe renal cell
CC       carcinoma, collecting duct carcinoma with medullary carcinoma of the
CC       kidney, and unclassified renal cell carcinoma. Clear cell renal cell
CC       carcinoma is the most common 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       variants affecting the gene represented in this entry. Defects of SETD2
CC       are associated with loss of DNA methylation at non-promoter regions
CC       (PubMed:23792563). SETD2 defects lead to aberrant and reduced
CC       nucleosome compaction and chromatin association of key replication
CC       proteins, such as MCM7 and DNA polymerase delta, leading to hinder
CC       replication fork progression and prevent loading of RAD51 homologous
CC       recombination repair factor at DNA breaks (PubMed:25728682).
CC       {ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}.
CC   -!- DISEASE: Luscan-Lumish syndrome (LLS) [MIM:616831]: An autosomal
CC       dominant syndrome with a variable phenotype. Clinical features include
CC       macrocephaly, distinctive facial appearance, postnatal overgrowth,
CC       various degrees of learning difficulties, autism spectrum disorder, and
CC       intellectual disability. {ECO:0000269|PubMed:23160955,
CC       ECO:0000269|PubMed:24852293, ECO:0000269|PubMed:26084711,
CC       ECO:0000269|PubMed:27317772}. Note=The disease may be caused by
CC       variants affecting the gene represented in this entry.
CC   -!- DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of
CC       acute leukemia, a cancer of the white blood cells. ALL is a malignant
CC       disease of bone marrow and the most common malignancy diagnosed in
CC       children. The malignant cells are lymphoid precursor cells
CC       (lymphoblasts) that are arrested in an early stage of development. The
CC       lymphoblasts replace the normal marrow elements, resulting in a marked
CC       decrease in the production of normal blood cells. Consequently, anemia,
CC       thrombocytopenia, and neutropenia occur to varying degrees. The
CC       lymphoblasts also proliferate in organs other than the marrow,
CC       particularly the liver, spleen, and lymphnodes.
CC       {ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24662245}. Note=The
CC       disease may be caused by variants affecting distinct genetic loci,
CC       including the gene represented in this entry.
CC   -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of
CC       acute leukemia, a cancer of the white blood cells. AML is a malignant
CC       disease of bone marrow characterized by maturational arrest of
CC       hematopoietic precursors at an early stage of development. Clonal
CC       expansion of myeloid blasts occurs in bone marrow, blood, and other
CC       tissue. Myelogenous leukemias develop from changes in cells that
CC       normally produce neutrophils, basophils, eosinophils and monocytes.
CC       {ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:24509477}. Note=The
CC       disease may be caused by variants affecting distinct genetic loci,
CC       including the gene represented in this entry.
CC   -!- DISEASE: Intellectual developmental disorder, autosomal dominant 70
CC       (MRD70) [MIM:620157]: An autosomal dominant disorder characterized by
CC       mild global developmental delay, moderately impaired intellectual
CC       disability with speech difficulties, and behavioral abnormalities.
CC       {ECO:0000269|PubMed:32710489}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Rabin-Pappas syndrome (RAPAS) [MIM:620155]: An autosomal
CC       dominant neurodevelopmental disorder characterized by severely impaired
CC       global development, intellectual disability, microcephaly, facial
CC       dysmorphism, and variable congenital anomalies affecting the skeletal,
CC       genitourinary, cardiac, and other organ systems.
CC       {ECO:0000269|PubMed:32710489}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC       superfamily. Histone-lysine methyltransferase family. SET2 subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF29041.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAH72440.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI17163.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI17165.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAT77612.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAT77613.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAB15367.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAC28349.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAD38601.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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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   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   PDB; 6J9J; X-ray; 1.78 A; A=1447-1703.
DR   PDB; 6VDB; X-ray; 2.30 A; A=1433-1711.
DR   PDB; 7EA8; EM; 3.10 A; L=1452-1696.
DR   PDB; 7EVR; X-ray; 1.80 A; B/D=2167-2192.
DR   PDB; 7EVS; X-ray; 1.60 A; C/D=2180-2192.
DR   PDB; 7LZB; X-ray; 2.28 A; A=1434-1711.
DR   PDB; 7LZD; X-ray; 1.80 A; A=1434-1711.
DR   PDB; 7LZF; X-ray; 2.47 A; A=1434-1711.
DR   PDB; 7TY2; X-ray; 2.44 A; A=1434-1711.
DR   PDB; 7TY3; X-ray; 2.30 A; A=1434-1711.
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   PDBsum; 6J9J; -.
DR   PDBsum; 6VDB; -.
DR   PDBsum; 7EA8; -.
DR   PDBsum; 7EVR; -.
DR   PDBsum; 7EVS; -.
DR   PDBsum; 7LZB; -.
DR   PDBsum; 7LZD; -.
DR   PDBsum; 7LZF; -.
DR   PDBsum; 7TY2; -.
DR   PDBsum; 7TY3; -.
DR   AlphaFoldDB; Q9BYW2; -.
DR   BMRB; Q9BYW2; -.
DR   EMDB; EMD-31040; -.
DR   SMR; Q9BYW2; -.
DR   BioGRID; 118845; 127.
DR   IntAct; Q9BYW2; 57.
DR   MINT; Q9BYW2; -.
DR   STRING; 9606.ENSP00000386759; -.
DR   BindingDB; Q9BYW2; -.
DR   ChEMBL; CHEMBL3108647; -.
DR   GlyGen; Q9BYW2; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q9BYW2; -.
DR   PhosphoSitePlus; Q9BYW2; -.
DR   SwissPalm; Q9BYW2; -.
DR   BioMuta; SETD2; -.
DR   DMDM; 296452963; -.
DR   OGP; Q9BYW2; -.
DR   EPD; Q9BYW2; -.
DR   jPOST; Q9BYW2; -.
DR   MassIVE; Q9BYW2; -.
DR   MaxQB; Q9BYW2; -.
DR   PaxDb; 9606-ENSP00000386759; -.
DR   PeptideAtlas; Q9BYW2; -.
DR   ProteomicsDB; 79730; -. [Q9BYW2-1]
DR   ProteomicsDB; 79731; -. [Q9BYW2-2]
DR   ProteomicsDB; 79732; -. [Q9BYW2-3]
DR   Pumba; Q9BYW2; -.
DR   ABCD; Q9BYW2; 1 sequenced antibody.
DR   Antibodypedia; 29842; 401 antibodies from 34 providers.
DR   DNASU; 29072; -.
DR   Ensembl; ENST00000409792.4; ENSP00000386759.3; ENSG00000181555.22. [Q9BYW2-1]
DR   GeneID; 29072; -.
DR   KEGG; hsa:29072; -.
DR   MANE-Select; ENST00000409792.4; ENSP00000386759.3; NM_014159.7; NP_054878.5.
DR   UCSC; uc003cqs.4; human. [Q9BYW2-1]
DR   AGR; HGNC:18420; -.
DR   CTD; 29072; -.
DR   DisGeNET; 29072; -.
DR   GeneCards; SETD2; -.
DR   GeneReviews; SETD2; -.
DR   HGNC; HGNC:18420; SETD2.
DR   HPA; ENSG00000181555; Low tissue specificity.
DR   MalaCards; SETD2; -.
DR   MIM; 144700; phenotype.
DR   MIM; 601626; phenotype.
DR   MIM; 612778; gene.
DR   MIM; 613065; phenotype.
DR   MIM; 616831; phenotype.
DR   MIM; 620155; phenotype.
DR   MIM; 620157; phenotype.
DR   neXtProt; NX_Q9BYW2; -.
DR   OpenTargets; ENSG00000181555; -.
DR   Orphanet; 597738; Luscan-Lumish syndrome.
DR   Orphanet; 597743; SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome.
DR   Orphanet; 821; Sotos syndrome.
DR   PharmGKB; PA143485612; -.
DR   VEuPathDB; HostDB:ENSG00000181555; -.
DR   eggNOG; KOG4442; Eukaryota.
DR   GeneTree; ENSGT00940000160086; -.
DR   HOGENOM; CLU_000810_1_0_1; -.
DR   InParanoid; Q9BYW2; -.
DR   OMA; VAYDRIQ; -.
DR   OrthoDB; 950362at2759; -.
DR   PhylomeDB; Q9BYW2; -.
DR   TreeFam; TF106477; -.
DR   BioCyc; MetaCyc:HS17695-MONOMER; -.
DR   BRENDA; 2.1.1.359; 2681.
DR   PathwayCommons; Q9BYW2; -.
DR   Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR   SignaLink; Q9BYW2; -.
DR   SIGNOR; Q9BYW2; -.
DR   BioGRID-ORCS; 29072; 309 hits in 1183 CRISPR screens.
DR   ChiTaRS; SETD2; human.
DR   EvolutionaryTrace; Q9BYW2; -.
DR   GeneWiki; SETD2; -.
DR   GenomeRNAi; 29072; -.
DR   Pharos; Q9BYW2; Tchem.
DR   PRO; PR:Q9BYW2; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q9BYW2; Protein.
DR   Bgee; ENSG00000181555; Expressed in tendon of biceps brachii and 210 other cell types or tissues.
DR   ExpressionAtlas; Q9BYW2; baseline and differential.
DR   Genevisible; Q9BYW2; HS.
DR   GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IC:UniProt.
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:0140938; F:histone H3 methyltransferase activity; TAS:Reactome.
DR   GO; GO:0046975; F:histone H3K36 methyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0140955; F:histone H3K36 trimethyltransferase activity; IEA:UniProtKB-EC.
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: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:0018023; P:peptidyl-lysine trimethylation; IDA:UniProtKB.
DR   GO; GO:0060039; P:pericardium development; IEA:Ensembl.
DR   GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProt.
DR   GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR   GO; GO:0045778; P:positive regulation of ossification; IEA:Ensembl.
DR   GO; GO:0032465; P:regulation of cytokinesis; IDA:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
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:0043279; P:response to alkaloid; IEA:Ensembl.
DR   GO; GO:0010038; P:response to metal ion; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
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 by RNA polymerase II; IMP:UniProtKB.
DR   CDD; cd19172; SET_SETD2; 1.
DR   CDD; cd00201; WW; 1.
DR   Gene3D; 2.20.70.10; -; 1.
DR   Gene3D; 1.20.930.10; Conserved domain common to transcription factors TFIIS, elongin A, CRSP70; 1.
DR   Gene3D; 2.170.270.10; SET domain; 1.
DR   Gene3D; 1.10.1740.100; Set2, Rpb1 interacting domain; 1.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR046341; SET_dom_sf.
DR   InterPro; IPR044437; SETD2/Set2_SET.
DR   InterPro; IPR042294; SETD2_animal.
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   PANTHER; PTHR46711; HISTONE-LYSINE N-METHYLTRANSFERASE SETD2; 1.
DR   PANTHER; PTHR46711:SF1; HISTONE-LYSINE N-METHYLTRANSFERASE SETD2; 1.
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; SSF82199; SET domain; 1.
DR   SUPFAM; SSF51045; WW domain; 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; Coiled coil;
KW   Developmental protein; Differentiation; Disease variant; DNA damage;
KW   DNA repair; Host-virus interaction; Immunity; Innate immunity;
KW   Intellectual disability; Isopeptide bond; Metal-binding; Methyltransferase;
KW   Nucleus; Phosphoprotein; Reference proteome; S-adenosyl-L-methionine;
KW   Transcription; Transcription regulation; Transferase; Tumor suppressor;
KW   Ubl conjugation; Zinc.
FT   CHAIN           1..2564
FT                   /note="Histone-lysine N-methyltransferase SETD2"
FT                   /id="PRO_0000252367"
FT   DOMAIN          1494..1548
FT                   /note="AWS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00562"
FT   DOMAIN          1550..1667
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   DOMAIN          1674..1690
FT                   /note="Post-SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT   DOMAIN          2389..2422
FT                   /note="WW"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT   REGION          1..30
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          180..211
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          272..561
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          607..626
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          964..995
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1036..1101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1133..1233
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1264..1352
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1393..1443
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1418..1714
FT                   /note="Interaction with TUBA1A"
FT                   /evidence="ECO:0000269|PubMed:27518565"
FT   REGION          1831..1872
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1921..2142
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2137..2366
FT                   /note="Low charge region"
FT                   /evidence="ECO:0000269|PubMed:16118227"
FT   REGION          2439..2465
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2457..2564
FT                   /note="Interaction with POLR2A"
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   COILED          2117..2146
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        185..201
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        276..297
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        298..327
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        340..411
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        424..471
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        486..526
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        544..560
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        967..993
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1061..1094
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1140..1154
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1164..1179
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1211..1233
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1393..1432
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1831..1867
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1924..1949
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1952..1971
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2011..2046
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2055..2080
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2090..2130
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2449..2465
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         1499
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1501
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1516
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1516
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1520
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1529
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1533
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1539
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1560..1562
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4H12, ECO:0007744|PDB:5JJY,
FT                   ECO:0007744|PDB:5JLB, ECO:0007744|PDB:5JLE,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1603..1605
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4H12, ECO:0007744|PDB:5JJY,
FT                   ECO:0007744|PDB:5JLB, ECO:0007744|PDB:5JLE,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1628..1629
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4H12, ECO:0007744|PDB:5JJY,
FT                   ECO:0007744|PDB:5JLB, ECO:0007744|PDB:5JLE,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1631
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1676
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4H12, ECO:0007744|PDB:5JJY,
FT                   ECO:0007744|PDB:5JLB, ECO:0007744|PDB:5JLE,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1678
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1679
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4H12, ECO:0007744|PDB:5JJY,
FT                   ECO:0007744|PDB:5JLB, ECO:0007744|PDB:5JLE,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1680
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   BINDING         1685
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:28256625,
FT                   ECO:0007744|PDB:4FMU, ECO:0007744|PDB:4H12,
FT                   ECO:0007744|PDB:5JJY, ECO:0007744|PDB:5JLB,
FT                   ECO:0007744|PDB:5JLE, ECO:0007744|PDB:5V21,
FT                   ECO:0007744|PDB:5V22"
FT   MOD_RES         131
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         321
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT   MOD_RES         323
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:21406692"
FT   MOD_RES         344
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         422
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         532
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         614
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         624
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         626
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         698
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         708
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   MOD_RES         744
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         754
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1098
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1228
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18220336,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT   MOD_RES         1413
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1415
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1417
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1696
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1844
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1845
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1853
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         1872
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT   MOD_RES         1888
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1952
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1980
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1988
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         1995
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:E9Q5F9"
FT   MOD_RES         2080
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         2082
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT   CROSSLNK        359
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        637
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:25755297,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        776
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   VAR_SEQ         1573..2564
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_020914"
FT   VAR_SEQ         1715..2564
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.7"
FT                   /id="VSP_020915"
FT   VARIANT         2
FT                   /note="K -> R (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079054"
FT   VARIANT         19
FT                   /note="E -> G (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079055"
FT   VARIANT         70..2564
FT                   /note="Missing (in AML; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079056"
FT   VARIANT         226
FT                   /note="P -> S (in ALL; uncertain significance; somatic
FT                   mutation; dbSNP:rs780963440)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079057"
FT   VARIANT         267
FT                   /note="V -> I (in ALL; uncertain significance; somatic
FT                   mutation; dbSNP:rs186148199)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079058"
FT   VARIANT         470
FT                   /note="S -> P (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079059"
FT   VARIANT         488
FT                   /note="Y -> C (found in a patient with autism; uncertain
FT                   significance; dbSNP:rs757781388)"
FT                   /evidence="ECO:0000269|PubMed:26637798"
FT                   /id="VAR_078707"
FT   VARIANT         499
FT                   /note="T -> A (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079060"
FT   VARIANT         761
FT                   /note="M -> I (in ALL; uncertain significance; somatic
FT                   mutation; dbSNP:rs188887061)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079061"
FT   VARIANT         768
FT                   /note="V -> L (in dbSNP:rs9311404)"
FT                   /id="VAR_027839"
FT   VARIANT         794..2564
FT                   /note="Missing (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079062"
FT   VARIANT         800
FT                   /note="S -> N (in AML; uncertain significance; somatic
FT                   mutation; dbSNP:rs1169288572)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079063"
FT   VARIANT         902
FT                   /note="E -> Q (in dbSNP:rs58906143)"
FT                   /id="VAR_061216"
FT   VARIANT         1076
FT                   /note="S -> P (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079064"
FT   VARIANT         1093
FT                   /note="S -> G (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079065"
FT   VARIANT         1171
FT                   /note="T -> A (in ALL; uncertain significance; somatic
FT                   mutation; dbSNP:rs540476365)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079066"
FT   VARIANT         1351
FT                   /note="D -> G (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079067"
FT   VARIANT         1365
FT                   /note="G -> E (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079068"
FT   VARIANT         1397
FT                   /note="D -> G (in AML; uncertain significance; somatic
FT                   mutation; dbSNP:rs754921650)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079069"
FT   VARIANT         1416..2564
FT                   /note="Missing (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079070"
FT   VARIANT         1453
FT                   /note="D -> N (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079071"
FT   VARIANT         1493
FT                   /note="D -> N (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079072"
FT   VARIANT         1496..2564
FT                   /note="Missing (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079073"
FT   VARIANT         1609
FT                   /note="L -> P (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079074"
FT   VARIANT         1654
FT                   /note="K -> Q (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079075"
FT   VARIANT         1663
FT                   /note="T -> M (in ALL; uncertain significance; somatic
FT                   mutation; dbSNP:rs1478147351)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079076"
FT   VARIANT         1733
FT                   /note="N -> D (in RCC; defects in recruitment of the MutS
FT                   alpha complex)"
FT                   /evidence="ECO:0000269|PubMed:23622243"
FT                   /id="VAR_069812"
FT   VARIANT         1740
FT                   /note="R -> Q (in MRD70)"
FT                   /evidence="ECO:0000269|PubMed:32710489"
FT                   /id="VAR_087881"
FT   VARIANT         1740
FT                   /note="R -> W (in RAPAS)"
FT                   /evidence="ECO:0000269|PubMed:32710489"
FT                   /id="VAR_087882"
FT   VARIANT         1769
FT                   /note="S -> P (in RCC; defects in recruitment of the MutS
FT                   alpha complex)"
FT                   /evidence="ECO:0000269|PubMed:23622243"
FT                   /id="VAR_069813"
FT   VARIANT         1804
FT                   /note="L -> S (in AML; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079077"
FT   VARIANT         1815
FT                   /note="L -> W (in LLS; uncertain significance;
FT                   dbSNP:rs869025570)"
FT                   /evidence="ECO:0000269|PubMed:24852293"
FT                   /id="VAR_076536"
FT   VARIANT         1821
FT                   /note="L -> P (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079078"
FT   VARIANT         1868
FT                   /note="A -> D (in dbSNP:rs11721074)"
FT                   /id="VAR_027840"
FT   VARIANT         1915
FT                   /note="V -> A (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079079"
FT   VARIANT         1920
FT                   /note="E -> V (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079080"
FT   VARIANT         1962
FT                   /note="P -> L (in dbSNP:rs4082155)"
FT                   /evidence="ECO:0000269|PubMed:11214970,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_027841"
FT   VARIANT         2077..2564
FT                   /note="Missing (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079081"
FT   VARIANT         2122
FT                   /note="R -> W (in AML; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079082"
FT   VARIANT         2214
FT                   /note="T -> A (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079083"
FT   VARIANT         2325..2564
FT                   /note="Missing (in AML; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079084"
FT   VARIANT         2361
FT                   /note="P -> S (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079085"
FT   VARIANT         2505
FT                   /note="F -> L (in AML; uncertain significance; somatic
FT                   mutation; impairs interaction with hyperphosphorylated
FT                   POLR2A)"
FT                   /evidence="ECO:0000269|PubMed:16314571,
FT                   ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079086"
FT   VARIANT         2524..2564
FT                   /note="Missing (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24509477"
FT                   /id="VAR_079087"
FT   VARIANT         2546..2564
FT                   /note="Missing (in ALL; uncertain significance; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:24662245"
FT                   /id="VAR_079088"
FT   MUTAGEN         1589
FT                   /note="F->A: Strongly reduced methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:27474439"
FT   MUTAGEN         1604
FT                   /note="Y->A: Increased methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:27474439"
FT   MUTAGEN         1625
FT                   /note="R->H,G: Loss of methyltransferase activity.
FT                   Abolishes ability to monomethylate STAT1."
FT                   /evidence="ECO:0000269|PubMed:16118227,
FT                   ECO:0000269|PubMed:28753426"
FT   MUTAGEN         1631
FT                   /note="C->A: Does not affect methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:28753426"
FT   MUTAGEN         1636
FT                   /note="E->A: Increased methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:27474439"
FT   MUTAGEN         1637
FT                   /note="T->A: Increased methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:27474439"
FT   MUTAGEN         1668
FT                   /note="F->A: Strongly reduced methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439"
FT   MUTAGEN         1669
FT                   /note="Q->A: Loss of methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:23043551"
FT   MUTAGEN         1670
FT                   /note="R->A,V,L,I,F: Impaired methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:23043551"
FT   MUTAGEN         1670
FT                   /note="R->P,W,K,Q: Loss of methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:23043551"
FT   MUTAGEN         1671
FT                   /note="Y->A: Strongly reduced methyltransferase activity."
FT                   /evidence="ECO:0000269|PubMed:23043551,
FT                   ECO:0000269|PubMed:27474439"
FT   MUTAGEN         2475
FT                   /note="R->A: Does not affect interaction with
FT                   hyperphosphorylated POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2476
FT                   /note="K->A: Does not affect interaction with
FT                   hyperphosphorylated POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2480
FT                   /note="Q->A: Does not affect interaction with
FT                   hyperphosphorylated POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2481
FT                   /note="F->A: Does not affect interaction with
FT                   hyperphosphorylated POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2483
FT                   /note="V->A: Impairs interaction with hyperphosphorylated
FT                   POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2506
FT                   /note="K->A: Impairs interaction with hyperphosphorylated
FT                   POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2510
FT                   /note="R->A: Impairs interaction with hyperphosphorylated
FT                   POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2514
FT                   /note="H->A: Impairs interaction with hyperphosphorylated
FT                   POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2515
FT                   /note="G->A,T: Does not affect interaction with
FT                   hyperphosphorylated POLR2A."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2528
FT                   /note="E->A: Increases interaction with hyperphosphorylated
FT                   POLR2A; when associated with A-2531."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   MUTAGEN         2531
FT                   /note="E->A: Increases interaction with hyperphosphorylated
FT                   POLR2A; when associated with A-2528."
FT                   /evidence="ECO:0000269|PubMed:16314571"
FT   CONFLICT        448
FT                   /note="R -> Q (in Ref. 2; BAD18522)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        455
FT                   /note="A -> V (in Ref. 3; CAD38601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        912
FT                   /note="L -> P (in Ref. 2; BAB15367)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        964
FT                   /note="E -> K (in Ref. 4; CAC28349, 6; AAT77612 and 7;
FT                   AAT77613)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1080
FT                   /note="M -> I (in Ref. 2; BAC87131)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1080
FT                   /note="M -> T (in Ref. 3; CAD38601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1212
FT                   /note="V -> F (in Ref. 2; BAD18522)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1269
FT                   /note="T -> A (in Ref. 4; CAC28349, 6; AAT77612 and 7;
FT                   AAT77613)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1338
FT                   /note="E -> G (in Ref. 2; BAB15367)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1498
FT                   /note="Q -> R (in Ref. 3; CAD38601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1706
FT                   /note="K -> N (in Ref. 10; AAF29041)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1736
FT                   /note="L -> P (in Ref. 4; CAC28349 and 6; AAT77612)"
FT                   /evidence="ECO:0000305"
FT   STRAND          1448..1450
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   HELIX           1451..1455
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   HELIX           1457..1465
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1472..1474
FT                   /evidence="ECO:0007829|PDB:7EA8"
FT   STRAND          1480..1483
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   TURN            1490..1493
FT                   /evidence="ECO:0007829|PDB:7EA8"
FT   HELIX           1506..1511
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   HELIX           1521..1524
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1531..1533
FT                   /evidence="ECO:0007829|PDB:5LSX"
FT   HELIX           1536..1538
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1539..1541
FT                   /evidence="ECO:0007829|PDB:5JLE"
FT   TURN            1543..1547
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1552..1556
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1558..1560
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1562..1568
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1575..1578
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1582..1584
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   HELIX           1586..1598
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1606..1610
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1613..1616
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1618..1621
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   HELIX           1623..1626
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1634..1642
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1645..1654
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1661..1664
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   HELIX           1667..1670
FT                   /evidence="ECO:0007829|PDB:5LT7"
FT   STRAND          1672..1674
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          1675..1677
FT                   /evidence="ECO:0007829|PDB:5LT7"
FT   STRAND          1682..1684
FT                   /evidence="ECO:0007829|PDB:7EA8"
FT   STRAND          1687..1691
FT                   /evidence="ECO:0007829|PDB:5LT7"
FT   HELIX           1697..1700
FT                   /evidence="ECO:0007829|PDB:5JLB"
FT   STRAND          2172..2175
FT                   /evidence="ECO:0007829|PDB:7EVR"
FT   TURN            2182..2185
FT                   /evidence="ECO:0007829|PDB:7EVS"
FT   STRAND          2377..2379
FT                   /evidence="ECO:0007829|PDB:2MDJ"
FT   HELIX           2386..2388
FT                   /evidence="ECO:0007829|PDB:2MDI"
FT   STRAND          2392..2399
FT                   /evidence="ECO:0007829|PDB:2MDC"
FT   TURN            2401..2403
FT                   /evidence="ECO:0007829|PDB:2MDJ"
FT   STRAND          2405..2409
FT                   /evidence="ECO:0007829|PDB:2MDC"
FT   TURN            2410..2413
FT                   /evidence="ECO:0007829|PDB:2MDC"
FT   STRAND          2414..2419
FT                   /evidence="ECO:0007829|PDB:2MDI"
FT   STRAND          2424..2428
FT                   /evidence="ECO:0007829|PDB:2MDC"
FT   HELIX           2463..2486
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   TURN            2487..2489
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   STRAND          2495..2498
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   HELIX           2502..2524
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   HELIX           2527..2529
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   HELIX           2534..2548
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   TURN            2549..2551
FT                   /evidence="ECO:0007829|PDB:2A7O"
FT   HELIX           2557..2559
FT                   /evidence="ECO:0007829|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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