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 03-AUG-2022, entry version 183.
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 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 [43] {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 [44]
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 [45]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1435-1711 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND ZINC, AND DOMAIN.
RX PubMed=28256625; DOI=10.1038/srep43906;
RA Zhang Y., Shan C.M., Wang J., Bao K., Tong L., Jia S.;
RT "Molecular basis for the role of oncogenic histone mutations in modulating
RT H3K36 methylation.";
RL Sci. Rep. 7:43906-43906(2017).
RN [46]
RP VARIANT LLS TRP-1815.
RX PubMed=24852293; DOI=10.1136/jmedgenet-2014-102402;
RA Luscan A., Laurendeau I., Malan V., Francannet C., Odent S., 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 [47]
RP VARIANT CYS-488.
RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA Sestan N., Walsh C.A.;
RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates
RT Multiple Genetic Mechanisms.";
RL Neuron 88:910-917(2015).
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). Interacts with TUBA1A; the interaction is
CC independent on alpha-tubulin acetylation on 'Lys-40' (PubMed:27518565).
CC Interacts with STAT1 (PubMed:28753426). {ECO:0000269|PubMed:10958656,
CC ECO:0000269|PubMed:11461154, ECO:0000269|PubMed:16118227,
CC ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:18585004,
CC ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:19332550,
CC ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426,
CC 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 -!- 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};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; 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 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 AlphaFoldDB; Q9BYW2; -.
DR BMRB; Q9BYW2; -.
DR SMR; Q9BYW2; -.
DR BioGRID; 118845; 108.
DR IntAct; Q9BYW2; 37.
DR MINT; Q9BYW2; -.
DR STRING; 9606.ENSP00000386759; -.
DR BindingDB; Q9BYW2; -.
DR ChEMBL; CHEMBL3108647; -.
DR GlyGen; Q9BYW2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BYW2; -.
DR PhosphoSitePlus; Q9BYW2; -.
DR BioMuta; SETD2; -.
DR DMDM; 296452963; -.
DR OGP; Q9BYW2; -.
DR EPD; Q9BYW2; -.
DR jPOST; Q9BYW2; -.
DR MassIVE; Q9BYW2; -.
DR MaxQB; Q9BYW2; -.
DR PaxDb; Q9BYW2; -.
DR PeptideAtlas; Q9BYW2; -.
DR PRIDE; Q9BYW2; -.
DR ProteomicsDB; 79730; -. [Q9BYW2-1]
DR ProteomicsDB; 79731; -. [Q9BYW2-2]
DR ProteomicsDB; 79732; -. [Q9BYW2-3]
DR ABCD; Q9BYW2; 1 sequenced antibody.
DR Antibodypedia; 29842; 352 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 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 neXtProt; NX_Q9BYW2; -.
DR OpenTargets; ENSG00000181555; -.
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; TCMQHSK; -.
DR OrthoDB; 507784at2759; -.
DR PhylomeDB; Q9BYW2; -.
DR TreeFam; TF106477; -.
DR BioCyc; MetaCyc:HS17695-MON; -.
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; 283 hits in 1095 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 209 other tissues.
DR ExpressionAtlas; Q9BYW2; baseline and differential.
DR Genevisible; Q9BYW2; HS.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0035441; P:cell migration involved in vasculogenesis; IEA:Ensembl.
DR GO; GO:0060977; P:coronary vasculature morphogenesis; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0060669; P:embryonic placenta morphogenesis; IEA:Ensembl.
DR GO; GO:0035987; P:endodermal cell differentiation; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0097676; P:histone H3-K36 dimethylation; IDA:HGNC.
DR GO; GO:0097198; P:histone H3-K36 trimethylation; IDA:UniProtKB.
DR GO; GO:0048332; P:mesoderm morphogenesis; IEA:Ensembl.
DR GO; GO:1902850; P:microtubule cytoskeleton organization involved in mitosis; IDA:UniProtKB.
DR GO; GO:0006298; P:mismatch repair; IMP:UniProtKB.
DR GO; GO:0001763; P:morphogenesis of a branching structure; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0034728; P:nucleosome organization; IMP:UniProtKB.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IDA:UniProtKB.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; IDA:UniProtKB.
DR GO; GO:0060039; P:pericardium development; IEA:Ensembl.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; IDA:UniProtKB.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO: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:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB.
DR GO; GO:0048864; P:stem cell development; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
DR CDD; cd19172; SET_SETD2; 1.
DR CDD; cd00201; WW; 1.
DR Gene3D; 1.10.1740.100; -; 1.
DR Gene3D; 1.20.930.10; -; 1.
DR Gene3D; 2.170.270.10; -; 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; PTHR46711; 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; SSF51045; SSF51045; 1.
DR SUPFAM; SSF82199; SSF82199; 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; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079054"
FT VARIANT 19
FT /note="E -> G (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079055"
FT VARIANT 70..2564
FT /note="Missing (in AML; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079056"
FT VARIANT 226
FT /note="P -> S (in ALL; unknown pathological significance;
FT somatic mutation; dbSNP:rs780963440)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079057"
FT VARIANT 267
FT /note="V -> I (in ALL; unknown pathological significance;
FT somatic mutation; dbSNP:rs186148199)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079058"
FT VARIANT 470
FT /note="S -> P (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079059"
FT VARIANT 488
FT /note="Y -> C (found in a patient with autism; unknown
FT pathological significance; dbSNP:rs757781388)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078707"
FT VARIANT 499
FT /note="T -> A (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079060"
FT VARIANT 761
FT /note="M -> I (in ALL; unknown pathological significance;
FT somatic 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; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079062"
FT VARIANT 800
FT /note="S -> N (in AML; unknown pathological significance;
FT somatic 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; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079064"
FT VARIANT 1093
FT /note="S -> G (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079065"
FT VARIANT 1171
FT /note="T -> A (in ALL; unknown pathological significance;
FT somatic mutation; dbSNP:rs540476365)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079066"
FT VARIANT 1351
FT /note="D -> G (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079067"
FT VARIANT 1365
FT /note="G -> E (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079068"
FT VARIANT 1397
FT /note="D -> G (in AML; unknown pathological significance;
FT somatic mutation; dbSNP:rs754921650)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079069"
FT VARIANT 1416..2564
FT /note="Missing (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079070"
FT VARIANT 1453
FT /note="D -> N (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079071"
FT VARIANT 1493
FT /note="D -> N (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079072"
FT VARIANT 1496..2564
FT /note="Missing (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079073"
FT VARIANT 1609
FT /note="L -> P (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079074"
FT VARIANT 1654
FT /note="K -> Q (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079075"
FT VARIANT 1663
FT /note="T -> M (in ALL; unknown pathological significance;
FT somatic 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 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; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079077"
FT VARIANT 1815
FT /note="L -> W (in LLS; unknown pathological significance;
FT dbSNP:rs869025570)"
FT /evidence="ECO:0000269|PubMed:24852293"
FT /id="VAR_076536"
FT VARIANT 1821
FT /note="L -> P (in ALL; unknown pathological significance;
FT somatic 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; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079079"
FT VARIANT 1920
FT /note="E -> V (in ALL; unknown pathological significance;
FT somatic 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; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079081"
FT VARIANT 2122
FT /note="R -> W (in AML; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079082"
FT VARIANT 2214
FT /note="T -> A (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079083"
FT VARIANT 2325..2564
FT /note="Missing (in AML; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079084"
FT VARIANT 2361
FT /note="P -> S (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24662245"
FT /id="VAR_079085"
FT VARIANT 2505
FT /note="F -> L (in AML; Impairs interaction with
FT hyperphosphorylated POLR2A; unknown pathological
FT significance; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:16314571,
FT ECO:0000269|PubMed:24509477"
FT /id="VAR_079086"
FT VARIANT 2524..2564
FT /note="Missing (in ALL; unknown pathological significance;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:24509477"
FT /id="VAR_079087"
FT VARIANT 2546..2564
FT /note="Missing (in ALL; unknown pathological significance;
FT somatic 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
