GENTAUR Molecular Products.

 SETB1_HUMAN             Reviewed;        1291 AA.
 Q15047; A6NEW2; Q5SZD8; Q5SZD9; Q5SZE0; Q5SZE7; Q96GM9;
 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
 01-NOV-1996, sequence version 1.
 28-MAR-2018, entry version 196.
 RecName: Full=Histone-lysine N-methyltransferase SETDB1;
          EC=2.1.1.43;
 AltName: Full=ERG-associated protein with SET domain;
          Short=ESET;
 AltName: Full=Histone H3-K9 methyltransferase 4;
          Short=H3-K9-HMTase 4;
 AltName: Full=Lysine N-methyltransferase 1E;
 AltName: Full=SET domain bifurcated 1;
 Name=SETDB1; Synonyms=KIAA0067, KMT1E;
 Homo sapiens (Human).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
 Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
 Catarrhini; Hominidae; Homo.
 NCBI_TaxID=9606;
 [1]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
 TISSUE=Bone marrow;
 PubMed=7584044; DOI=10.1093/dnares/1.5.223;
 Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S.,
 Seki N., Kawarabayasi Y., Ishikawa K., Tabata S.;
 "Prediction of the coding sequences of unidentified human genes. II.
 The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by
 analysis of cDNA clones from human cell line KG-1.";
 DNA Res. 1:223-229(1994).
 [2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 PubMed=16710414; DOI=10.1038/nature04727;
 Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
 Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
 Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
 McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
 Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
 Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
 Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
 Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
 Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
 Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
 Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
 Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
 Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
 Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
 Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
 Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
 Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
 Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
 Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
 Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
 Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
 Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
 Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
 Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
 Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
 Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
 Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
 Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
 Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
 Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
 Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
 Beck S., Rogers J., Bentley D.R.;
 "The DNA sequence and biological annotation of human chromosome 1.";
 Nature 441:315-321(2006).
 [3]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
 Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
 Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
 Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
 Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
 Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
 Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
 Venter J.C.;
 Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
 [4]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND
 VARIANT SER-506.
 TISSUE=Muscle, and Uterus;
 PubMed=15489334; DOI=10.1101/gr.2596504;
 The MGC Project Team;
 "The status, quality, and expansion of the NIH full-length cDNA
 project: the Mammalian Gene Collection (MGC).";
 Genome Res. 14:2121-2127(2004).
 [5]
 CHARACTERIZATION, MUTAGENESIS OF 729-CYS--CYS-731; HIS-1224; CYS-1226
 AND CYS-1279, AND INTERACTION WITH TRIM28.
 PubMed=11959841; DOI=10.1101/gad.973302;
 Schultz D.C., Ayyanathan K., Negorev D., Maul G.G., Rauscher F.J. III;
 "SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific
 methyltransferase that contributes to HP1-mediated silencing of
 euchromatic genes by KRAB zinc-finger proteins.";
 Genes Dev. 16:919-932(2002).
 [6]
 FUNCTION.
 PubMed=12869583; DOI=10.1101/gad.1102803;
 Ayyanathan K., Lechner M.S., Bell P., Maul G.G., Schultz D.C.,
 Yamada Y., Tanaka K., Torigoe K., Rauscher F.J. III;
 "Regulated recruitment of HP1 to a euchromatic gene induces
 mitotically heritable, epigenetic gene silencing: a mammalian cell
 culture model of gene variegation.";
 Genes Dev. 17:1855-1869(2003).
 [7]
 IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH
 ATF7IP.
 PubMed=14536086; DOI=10.1016/j.molcel.2003.08.007;
 Wang H., An W., Cao R., Xia L., Erdjument-Bromage H., Chatton B.,
 Tempst P., Roeder R.G., Zhang Y.;
 "mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9
 of histone H3 to cause transcriptional repression.";
 Mol. Cell 12:475-487(2003).
 [8]
 FUNCTION, AND INTERACTION WITH MBD1 AND CHAF1A.
 PubMed=15327775; DOI=10.1016/j.molcel.2004.06.043;
 Sarraf S.A., Stancheva I.;
 "Methyl-CpG binding protein MBD1 couples histone H3 methylation at
 lysine 9 by SETDB1 to DNA replication and chromatin assembly.";
 Mol. Cell 15:595-605(2004).
 [9]
 INTERACTION WITH CBX1 AND CBX5.
 PubMed=15899859; DOI=10.1128/MCB.25.11.4552-4564.2005;
 Verschure P.J., van der Kraan I., de Leeuw W., van der Vlag J.,
 Carpenter A.E., Belmont A.S., van Driel R.;
 "In vivo HP1 targeting causes large-scale chromatin condensation and
 enhanced histone lysine methylation.";
 Mol. Cell. Biol. 25:4552-4564(2005).
 [10]
 INTERACTION WITH MBD1.
 PubMed=17066076; DOI=10.1038/sj.emboj.7601404;
 Lyst M.J., Nan X., Stancheva I.;
 "Regulation of MBD1-mediated transcriptional repression by SUMO and
 PIAS proteins.";
 EMBO J. 25:5317-5328(2006).
 [11]
 INTERACTION WITH ATF7IP AND ATF7IP2.
 PubMed=15691849; DOI=10.1074/jbc.M413654200;
 Ichimura T., Watanabe S., Sakamoto Y., Aoto T., Fujita N., Nakao M.;
 "Transcriptional repression and heterochromatin formation by MBD1 and
 MCAF/AM family proteins.";
 J. Biol. Chem. 280:13928-13935(2005).
 [12]
 INTERACTION WITH DNMT3A AND DNMT3B.
 PubMed=16682412; DOI=10.1074/jbc.M513249200;
 Li H., Rauch T., Chen Z.-X., Szabo P.E., Riggs A.D., Pfeifer G.P.;
 "The histone methyltransferase SETDB1 and the DNA methyltransferase
 DNMT3A interact directly and localize to promoters silenced in cancer
 cells.";
 J. Biol. Chem. 281:19489-19500(2006).
 [13]
 INTERACTION WITH SUMO2.
 PubMed=16567619; DOI=10.1073/pnas.0601066103;
 Rosendorff A., Sakakibara S., Lu S., Kieff E., Xuan Y., DiBacco A.,
 Shi Y., Shi Y., Gill G.;
 "NXP-2 association with SUMO-2 depends on lysines required for
 transcriptional repression.";
 Proc. Natl. Acad. Sci. U.S.A. 103:5308-5313(2006).
 [14]
 EXPRESSION IN HUNTINGTON DISEASE.
 PubMed=17142323; DOI=10.1073/pnas.0606373103;
 Ryu H., Lee J., Hagerty S.W., Soh B.Y., McAlpin S.E., Cormier K.A.,
 Smith K.M., Ferrante R.J.;
 "ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in
 Huntington's disease.";
 Proc. Natl. Acad. Sci. U.S.A. 103:19176-19181(2006).
 [15]
 FUNCTION, INTERACTION WITH CHD7; NLK1 AND PPARG, PHOSPHORYLATION AT
 THR-976, AND MUTAGENESIS OF THR-976.
 PubMed=17952062; DOI=10.1038/ncb1647;
 Takada I., Mihara M., Suzawa M., Ohtake F., Kobayashi S., Igarashi M.,
 Youn M.Y., Takeyama K., Nakamura T., Mezaki Y., Takezawa S.,
 Yogiashi Y., Kitagawa H., Yamada G., Takada S., Minami Y., Shibuya H.,
 Matsumoto K., Kato S.;
 "A histone lysine methyltransferase activated by non-canonical Wnt
 signalling suppresses PPAR-gamma transactivation.";
 Nat. Cell Biol. 9:1273-1285(2007).
 [16]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1066, AND IDENTIFICATION
 BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Cervix carcinoma;
 PubMed=18220336; DOI=10.1021/pr0705441;
 Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
 Yates J.R. III;
 "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
 efficient phosphoproteomic analysis.";
 J. Proteome Res. 7:1346-1351(2008).
 [17]
 IDENTIFICATION IN A COMPLEX WITH REST; CDYL; WIZ; EHMT1 AND EHMT2.
 PubMed=19061646; DOI=10.1016/j.molcel.2008.10.025;
 Mulligan P., Westbrook T.F., Ottinger M., Pavlova N., Chang B.,
 Macia E., Shi Y.J., Barretina J., Liu J., Howley P.M., Elledge S.J.,
 Shi Y.;
 "CDYL bridges REST and histone methyltransferases for gene repression
 and suppression of cellular transformation.";
 Mol. Cell 32:718-726(2008).
 [18]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1066, AND IDENTIFICATION
 BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Cervix carcinoma;
 PubMed=18669648; DOI=10.1073/pnas.0805139105;
 Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
 Elledge S.J., Gygi S.P.;
 "A quantitative atlas of mitotic phosphorylation.";
 Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
 [19]
 INTERACTION WITH MPHOSPH8.
 PubMed=20871592; DOI=10.1038/emboj.2010.239;
 Kokura K., Sun L., Bedford M.T., Fang J.;
 "Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing
 and promotes tumour cell motility and invasion.";
 EMBO J. 29:3673-3687(2010).
 [20]
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=21269460; DOI=10.1186/1752-0509-5-17;
 Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
 Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
 "Initial characterization of the human central proteome.";
 BMC Syst. Biol. 5:17-17(2011).
 [21]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1066, AND IDENTIFICATION
 BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=21406692; DOI=10.1126/scisignal.2001570;
 Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
 Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
 Blagoev B.;
 "System-wide temporal characterization of the proteome and
 phosphoproteome of human embryonic stem cell differentiation.";
 Sci. Signal. 4:RS3-RS3(2011).
 [22]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1025 AND SER-1066, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Cervix carcinoma, and Erythroleukemia;
 PubMed=23186163; DOI=10.1021/pr300630k;
 Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
 Mohammed S.;
 "Toward a comprehensive characterization of a human cancer cell
 phosphoproteome.";
 J. Proteome Res. 12:260-271(2013).
 [23]
 FUNCTION, POSSIBLE IDENTIFICATION IN A COREPRESSOR COMPLEX, AND
 CHROMATIN-BINDING.
 PubMed=24623306; DOI=10.7554/eLife.02313;
 Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
 "A KRAS-directed transcriptional silencing pathway that mediates the
 CpG island methylator phenotype.";
 Elife 3:E02313-E02313(2014).
 [24]
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Liver;
 PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
 Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
 Wang L., Ye M., Zou H.;
 "An enzyme assisted RP-RPLC approach for in-depth analysis of human
 liver phosphoproteome.";
 J. Proteomics 96:253-262(2014).
 [25]
 METHYLATION [LARGE SCALE ANALYSIS] AT LYS-1170 AND LYS-1178, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Colon carcinoma;
 PubMed=24129315; DOI=10.1074/mcp.O113.027870;
 Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V.,
 Aguiar M., Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C.,
 Vemulapalli V., Bedford M.T., Comb M.J.;
 "Immunoaffinity enrichment and mass spectrometry analysis of protein
 methylation.";
 Mol. Cell. Proteomics 13:372-387(2014).
 [26]
 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032 AND LYS-1069, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=25218447; DOI=10.1038/nsmb.2890;
 Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
 Vertegaal A.C.;
 "Uncovering global SUMOylation signaling networks in a site-specific
 manner.";
 Nat. Struct. Mol. Biol. 21:927-936(2014).
 [27]
 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032, AND IDENTIFICATION BY
 MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=25114211; DOI=10.1073/pnas.1413825111;
 Impens F., Radoshevich L., Cossart P., Ribet D.;
 "Mapping of SUMO sites and analysis of SUMOylation changes induced by
 external stimuli.";
 Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
 [28]
 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032 AND LYS-1069, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
 Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
 Vertegaal A.C.;
 "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
 Cell Rep. 10:1778-1791(2015).
 [29]
 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032 AND LYS-1069, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=25755297; DOI=10.1074/mcp.O114.044792;
 Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
 Vertegaal A.C.;
 "System-wide analysis of SUMOylation dynamics in response to
 replication stress reveals novel small ubiquitin-like modified target
 proteins and acceptor lysines relevant for genome stability.";
 Mol. Cell. Proteomics 14:1419-1434(2015).
 [30]
 FUNCTION, INTERACTION WITH ATRX, AND FORMATION OF A COMPLEX WITH ATRX;
 TRIM28 AND ZNF274.
 PubMed=27029610; DOI=10.1080/15592294.2016.1169351;
 Valle-Garcia D., Qadeer Z.A., McHugh D.S., Ghiraldini F.G.,
 Chowdhury A.H., Hasson D., Dyer M.A., Recillas-Targa F., Bernstein E.;
 "ATRX binds to atypical chromatin domains at the 3' exons of zinc
 finger genes to preserve H3K9me3 enrichment.";
 Epigenetics 11:398-414(2016).
 [31]
 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-182; LYS-1032; LYS-1038;
 LYS-1069 AND LYS-1149, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
 SCALE ANALYSIS].
 PubMed=28112733; DOI=10.1038/nsmb.3366;
 Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
 Nielsen M.L.;
 "Site-specific mapping of the human SUMO proteome reveals co-
 modification with phosphorylation.";
 Nat. Struct. Mol. Biol. 24:325-336(2017).
 [32]
 X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 196-402.
 Structural genomics consortium (SGC);
 "The crystal structure of Tudor domain of human histone-lysine N-
 methyltransferase SETDB1.";
 Submitted (FEB-2009) to the PDB data bank.
 -!- FUNCTION: Histone methyltransferase that specifically
     trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation
     represents a specific tag for epigenetic transcriptional
     repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to
     methylated histones. Mainly functions in euchromatin regions,
     thereby playing a central role in the silencing of euchromatic
     genes. H3 'Lys-9' trimethylation is coordinated with DNA
     methylation. Probably forms a complex with MBD1 and ATF7IP that
     represses transcription and couples DNA methylation and histone
     'Lys-9' trimethylation. Its activity is dependent on MBD1 and is
     heritably maintained through DNA replication by being recruited by
     CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor
     recruited by KRAB zinc-finger proteins. Probably forms a
     corepressor complex required for activated KRAS-mediated promoter
     hypermethylation and transcriptional silencing of tumor suppressor
     genes (TSGs) or other tumor-related genes in colorectal cancer
     (CRC) cells (PubMed:24623306). Also required to maintain a
     transcriptionally repressive state of genes in undifferentiated
     embryonic stem cells (ESCs) (PubMed:24623306). Associates at
     promoter regions of tumor suppressor genes (TSGs) leading to their
     gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex
     may play a role in recruiting ATRX to the 3'-exons of zinc-finger
     coding genes with atypical chromatin signatures to establish or
     maintain/protect H3K9me3 at these transcriptionally active regions
     (PubMed:27029610). {ECO:0000269|PubMed:12869583,
     ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:15327775,
     ECO:0000269|PubMed:17952062, ECO:0000269|PubMed:24623306,
     ECO:0000269|PubMed:27029610}.
 -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] =
     S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
     {ECO:0000255|PROSITE-ProRule:PRU00906}.
 -!- SUBUNIT: Part of a complex containing at least CDYL, REST, WIZ,
     SETB1, EHMT1 and EHMT2 (PubMed:19061646). During DNA replication,
     it is recruited by SETDB1 to form a S phase-specific complex that
     facilitates methylation of H3 'Lys-9' during replication-coupled
     chromatin assembly and is at least composed of the CAF-1 subunit
     CHAF1A, MBD1 and SETDB1 (PubMed:15327775). Probably part of a
     corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1
     (PubMed:24623306). Interacts with TRIM28/TIF1B (PubMed:11959841).
     Interacts with ATF7IP and ATF7IP2; the interaction with ATF7IP is
     required to stimulate histone methyltransferase activity and
     facilitate the conversion of dimethylated to trimethylated H3
     'Lys-9' (PubMed:14536086, PubMed:15691849). Interacts with MBD1;
     interaction is abolished when MBD1 is sumoylated (PubMed:15327775,
     PubMed:17066076). Interacts with CBX1 and CBX5 (PubMed:15899859).
     Interacts with DNMT3A and DNMT3B (PubMed:16682412). Interacts with
     SUMO2. Interacts with CHD7, NLK1 and PPARG (PubMed:17952062).
     Interacts with MPHOSPH8 (PubMed:20871592). Interacts with ERG (By
     similarity). Interacts with HDAC1, HDAC2, SIN3A and SIN3B (By
     similarity). Interacts with ATRX. Forms a complex with ATRX,
     TRIM28 and ZNF274 (PubMed:27029610).
     {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:11959841,
     ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:15327775,
     ECO:0000269|PubMed:15691849, ECO:0000269|PubMed:15899859,
     ECO:0000269|PubMed:16567619, ECO:0000269|PubMed:16682412,
     ECO:0000269|PubMed:17066076, ECO:0000269|PubMed:17952062,
     ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:20871592,
     ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610}.
 -!- INTERACTION:
     P31749:AKT1; NbExp=9; IntAct=EBI-79691, EBI-296087;
     Q9Y6K1:DNMT3A; NbExp=7; IntAct=EBI-79691, EBI-923653;
     O75031:HSF2BP; NbExp=4; IntAct=EBI-11149962, EBI-7116203;
     Q9UIS9:MBD1; NbExp=3; IntAct=EBI-79691, EBI-867196;
     Q99549:MPHOSPH8; NbExp=3; IntAct=EBI-79691, EBI-2653928;
     Q8IUH5:ZDHHC17; NbExp=3; IntAct=EBI-9090795, EBI-524753;
 -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Associated with
     non-pericentromeric regions of chromatin. Excluded from nucleoli
     and islands of condensed chromatin.
 -!- ALTERNATIVE PRODUCTS:
     Event=Alternative splicing; Named isoforms=3;
     Name=1;
       IsoId=Q15047-1; Sequence=Displayed;
     Name=2;
       IsoId=Q15047-2; Sequence=VSP_002217, VSP_002218;
       Note=No experimental confirmation available.;
     Name=3;
       IsoId=Q15047-3; Sequence=VSP_034600;
       Note=No experimental confirmation available.;
 -!- TISSUE SPECIFICITY: Widely expressed. High expression in testis.
 -!- DOMAIN: The pre-SET, SET and post-SET domains are all required for
     methyltransferase activity. The 347-amino-acid insertion in the
     SET domain has no effect on the catalytic activity.
 -!- DOMAIN: Isoform 2 lacks all domains required for histone
     methyltransferase activity.
 -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that
     are arranged in a triangular cluster; some of these Cys residues
     contribute to the binding of two zinc ions within the cluster.
     {ECO:0000250}.
 -!- MISCELLANEOUS: Highly up-regulated in Huntington disease patients,
     suggesting that participates in the altered chromatin modulation
     and transcription dysfunction observed in Huntington disease. Its
     down-regulation has salubrious effects on patients, suggesting
     that it may be a promising treatment in Huntington disease
     patients.
 -!- SIMILARITY: Belongs to the class V-like SAM-binding
     methyltransferase superfamily. Histone-lysine methyltransferase
     family. Suvar3-9 subfamily. {ECO:0000255|PROSITE-
     ProRule:PRU00906}.
 -!- SEQUENCE CAUTION:
     Sequence=BAA06689.2; Type=Erroneous initiation; Evidence={ECO:0000305};
     Sequence=CAI13325.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
     Sequence=CAI13326.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
 -----------------------------------------------------------------------
 Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
 Distributed under the Creative Commons Attribution-NoDerivs License
 -----------------------------------------------------------------------
 EMBL; D31891; BAA06689.2; ALT_INIT; mRNA.
 EMBL; AL590133; CAI13325.1; ALT_SEQ; Genomic_DNA.
 EMBL; AL590133; CAI13326.1; ALT_SEQ; Genomic_DNA.
 EMBL; AL590133; CAI13327.1; -; Genomic_DNA.
 EMBL; AL590133; CAI13328.1; -; Genomic_DNA.
 EMBL; CH471121; EAW53506.1; -; Genomic_DNA.
 EMBL; BC009362; AAH09362.1; -; mRNA.
 EMBL; BC028671; AAH28671.1; -; mRNA.
 CCDS; CCDS44217.1; -. [Q15047-1]
 CCDS; CCDS58026.1; -. [Q15047-2]
 CCDS; CCDS972.1; -. [Q15047-3]
 RefSeq; NP_001138887.1; NM_001145415.1. [Q15047-1]
 RefSeq; NP_001230420.1; NM_001243491.1. [Q15047-2]
 RefSeq; NP_036564.3; NM_012432.3. [Q15047-3]
 RefSeq; XP_016858444.1; XM_017002955.1. [Q15047-2]
 UniGene; Hs.643565; -.
 PDB; 3DLM; X-ray; 1.77 A; A=196-402.
 PDB; 4X3S; X-ray; 1.60 A; C/D=1165-1174.
 PDB; 5KCH; X-ray; 1.70 A; A=196-403.
 PDB; 5KCO; X-ray; 1.47 A; A=196-403.
 PDB; 5KE2; X-ray; 1.56 A; A=196-402.
 PDB; 5KE3; X-ray; 1.70 A; A=196-402.
 PDB; 5KH6; X-ray; 2.05 A; A=196-400.
 PDB; 6AU2; X-ray; 1.63 A; A=196-402.
 PDB; 6AU3; X-ray; 1.80 A; A=196-402.
 PDB; 6BHD; X-ray; 1.25 A; A=190-410.
 PDB; 6BHE; X-ray; 1.35 A; A=190-410.
 PDB; 6BHG; X-ray; 1.45 A; A=190-410.
 PDB; 6BHH; X-ray; 1.85 A; A=190-410.
 PDB; 6BHI; X-ray; 1.40 A; A=190-410.
 PDB; 6BPI; X-ray; 1.64 A; A=196-402.
 PDBsum; 3DLM; -.
 PDBsum; 4X3S; -.
 PDBsum; 5KCH; -.
 PDBsum; 5KCO; -.
 PDBsum; 5KE2; -.
 PDBsum; 5KE3; -.
 PDBsum; 5KH6; -.
 PDBsum; 6AU2; -.
 PDBsum; 6AU3; -.
 PDBsum; 6BHD; -.
 PDBsum; 6BHE; -.
 PDBsum; 6BHG; -.
 PDBsum; 6BHH; -.
 PDBsum; 6BHI; -.
 PDBsum; 6BPI; -.
 ProteinModelPortal; Q15047; -.
 SMR; Q15047; -.
 BioGrid; 115202; 140.
 CORUM; Q15047; -.
 DIP; DIP-31029N; -.
 IntAct; Q15047; 122.
 MINT; Q15047; -.
 STRING; 9606.ENSP00000271640; -.
 BindingDB; Q15047; -.
 ChEMBL; CHEMBL2321646; -.
 iPTMnet; Q15047; -.
 PhosphoSitePlus; Q15047; -.
 BioMuta; SETDB1; -.
 DMDM; 25091210; -.
 EPD; Q15047; -.
 MaxQB; Q15047; -.
 PaxDb; Q15047; -.
 PeptideAtlas; Q15047; -.
 PRIDE; Q15047; -.
 Ensembl; ENST00000271640; ENSP00000271640; ENSG00000143379. [Q15047-1]
 Ensembl; ENST00000368962; ENSP00000357958; ENSG00000143379. [Q15047-2]
 Ensembl; ENST00000368969; ENSP00000357965; ENSG00000143379. [Q15047-3]
 GeneID; 9869; -.
 KEGG; hsa:9869; -.
 UCSC; uc001evu.3; human. [Q15047-1]
 CTD; 9869; -.
 DisGeNET; 9869; -.
 EuPathDB; HostDB:ENSG00000143379.12; -.
 GeneCards; SETDB1; -.
 HGNC; HGNC:10761; SETDB1.
 HPA; HPA018142; -.
 HPA; HPA058484; -.
 MIM; 604396; gene.
 neXtProt; NX_Q15047; -.
 OpenTargets; ENSG00000143379; -.
 PharmGKB; PA35679; -.
 eggNOG; KOG1141; Eukaryota.
 eggNOG; COG2940; LUCA.
 GeneTree; ENSGT00780000121845; -.
 HOVERGEN; HBG061013; -.
 InParanoid; Q15047; -.
 KO; K11421; -.
 OMA; TSMHQSR; -.
 OrthoDB; EOG091G014F; -.
 PhylomeDB; Q15047; -.
 TreeFam; TF106411; -.
 Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
 SIGNOR; Q15047; -.
 ChiTaRS; SETDB1; human.
 EvolutionaryTrace; Q15047; -.
 GeneWiki; SETDB1; -.
 GenomeRNAi; 9869; -.
 PRO; PR:Q15047; -.
 Proteomes; UP000005640; Chromosome 1.
 Bgee; ENSG00000143379; -.
 CleanEx; HS_SETDB1; -.
 ExpressionAtlas; Q15047; baseline and differential.
 Genevisible; Q15047; HS.
 GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
 GO; GO:0005829; C:cytosol; IDA:HPA.
 GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
 GO; GO:0005654; C:nucleoplasm; IDA:HPA.
 GO; GO:0005634; C:nucleus; IDA:HPA.
 GO; GO:0005886; C:plasma membrane; IDA:HPA.
 GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO; GO:0003677; F:DNA binding; IEA:InterPro.
 GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IEA:UniProtKB-EC.
 GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
 GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO; GO:0090309; P:positive regulation of methylation-dependent chromatin silencing; IMP:UniProtKB.
 GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
 GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
 GO; GO:0033273; P:response to vitamin; IEA:Ensembl.
 GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
 InterPro; IPR016177; DNA-bd_dom_sf.
 InterPro; IPR025796; Hist-Lys_N-MeTrfase_SETDB1.
 InterPro; IPR001739; Methyl_CpG_DNA-bd.
 InterPro; IPR003616; Post-SET_dom.
 InterPro; IPR007728; Pre-SET_dom.
 InterPro; IPR001214; SET_dom.
 InterPro; IPR002999; Tudor.
 Pfam; PF01429; MBD; 1.
 Pfam; PF05033; Pre-SET; 1.
 Pfam; PF00856; SET; 1.
 SMART; SM00391; MBD; 1.
 SMART; SM00468; PreSET; 1.
 SMART; SM00317; SET; 1.
 SMART; SM00333; TUDOR; 2.
 SUPFAM; SSF54171; SSF54171; 1.
 PROSITE; PS50982; MBD; 1.
 PROSITE; PS50868; POST_SET; 1.
 PROSITE; PS50867; PRE_SET; 1.
 PROSITE; PS51573; SAM_MT43_SUVAR39_1; 1.
 PROSITE; PS50280; SET; 1.
 1: Evidence at protein level;
 3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
 Coiled coil; Complete proteome; Isopeptide bond; Metal-binding;
 Methylation; Methyltransferase; Nucleus; Phosphoprotein; Polymorphism;
 Reference proteome; Repeat; Repressor; S-adenosyl-L-methionine;
 Transcription; Transcription regulation; Transferase; Ubl conjugation;
 Zinc.
 CHAIN         1   1291       Histone-lysine N-methyltransferase
                              SETDB1.
                              /FTId=PRO_0000186064.
 DOMAIN      257    320       Tudor 1.
 DOMAIN      347    403       Tudor 2.
 DOMAIN      594    665       MBD. {ECO:0000255|PROSITE-
                              ProRule:PRU00338}.
 DOMAIN      727    800       Pre-SET. {ECO:0000255|PROSITE-
                              ProRule:PRU00157}.
 DOMAIN      803   1266       SET. {ECO:0000255|PROSITE-
                              ProRule:PRU00190}.
 DOMAIN     1275   1291       Post-SET. {ECO:0000255|PROSITE-
                              ProRule:PRU00155}.
 REGION      813    815       S-adenosyl-L-methionine binding.
                              {ECO:0000250}.
 REGION     1223   1224       S-adenosyl-L-methionine binding.
                              {ECO:0000250}.
 COILED       18     64       {ECO:0000255}.
 METAL       729    729       Zinc 1. {ECO:0000250}.
 METAL       729    729       Zinc 2. {ECO:0000250}.
 METAL       731    731       Zinc 1. {ECO:0000250}.
 METAL       735    735       Zinc 1. {ECO:0000250}.
 METAL       735    735       Zinc 3. {ECO:0000250}.
 METAL       741    741       Zinc 1. {ECO:0000250}.
 METAL       743    743       Zinc 2. {ECO:0000250}.
 METAL       781    781       Zinc 2. {ECO:0000250}.
 METAL       781    781       Zinc 3. {ECO:0000250}.
 METAL       785    785       Zinc 2. {ECO:0000250}.
 METAL       787    787       Zinc 3. {ECO:0000250}.
 METAL       792    792       Zinc 3. {ECO:0000250}.
 METAL      1226   1226       Zinc 4. {ECO:0000250}.
 METAL      1279   1279       Zinc 4. {ECO:0000250}.
 METAL      1281   1281       Zinc 4. {ECO:0000250}.
 METAL      1286   1286       Zinc 4. {ECO:0000250}.
 BINDING     851    851       S-adenosyl-L-methionine.
                              {ECO:0000255|PROSITE-ProRule:PRU00190}.
 BINDING     853    853       S-adenosyl-L-methionine.
                              {ECO:0000255|PROSITE-ProRule:PRU00190}.
 BINDING    1220   1220       S-adenosyl-L-methionine.
                              {ECO:0000255|PROSITE-ProRule:PRU00190}.
 MOD_RES     112    112       Phosphoserine.
                              {ECO:0000250|UniProtKB:O88974}.
 MOD_RES     117    117       Phosphoserine.
                              {ECO:0000250|UniProtKB:O88974}.
 MOD_RES     120    120       Phosphothreonine.
                              {ECO:0000250|UniProtKB:O88974}.
 MOD_RES     976    976       Phosphothreonine; by NLK.
                              {ECO:0000305|PubMed:17952062}.
 MOD_RES    1025   1025       Phosphoserine.
                              {ECO:0000244|PubMed:23186163}.
 MOD_RES    1066   1066       Phosphoserine.
                              {ECO:0000244|PubMed:18220336,
                              ECO:0000244|PubMed:18669648,
                              ECO:0000244|PubMed:21406692,
                              ECO:0000244|PubMed:23186163}.
 MOD_RES    1170   1170       N6,N6,N6-trimethyllysine; alternate.
                              {ECO:0000244|PubMed:24129315}.
 MOD_RES    1170   1170       N6,N6-dimethyllysine; alternate.
                              {ECO:0000244|PubMed:24129315}.
 MOD_RES    1178   1178       N6,N6,N6-trimethyllysine; alternate.
                              {ECO:0000244|PubMed:24129315}.
 MOD_RES    1178   1178       N6,N6-dimethyllysine; alternate.
                              {ECO:0000244|PubMed:24129315}.
 CROSSLNK    182    182       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in SUMO2);
                              alternate. {ECO:0000244|PubMed:28112733}.
 CROSSLNK    182    182       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in ubiquitin);
                              alternate.
 CROSSLNK   1032   1032       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in SUMO1);
                              alternate. {ECO:0000244|PubMed:25114211}.
 CROSSLNK   1032   1032       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in SUMO2);
                              alternate. {ECO:0000244|PubMed:25218447,
                              ECO:0000244|PubMed:25755297,
                              ECO:0000244|PubMed:25772364,
                              ECO:0000244|PubMed:28112733}.
 CROSSLNK   1038   1038       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in SUMO2).
                              {ECO:0000244|PubMed:28112733}.
 CROSSLNK   1069   1069       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in SUMO2).
                              {ECO:0000244|PubMed:25218447,
                              ECO:0000244|PubMed:25755297,
                              ECO:0000244|PubMed:25772364,
                              ECO:0000244|PubMed:28112733}.
 CROSSLNK   1149   1149       Glycyl lysine isopeptide (Lys-Gly)
                              (interchain with G-Cter in SUMO2).
                              {ECO:0000244|PubMed:28112733}.
 VAR_SEQ     381    397       DDKRCEWIYRGSTRLEP -> VLFFSTILEAEVGGGGT
                              (in isoform 2).
                              {ECO:0000303|PubMed:15489334}.
                              /FTId=VSP_002217.
 VAR_SEQ     398   1291       Missing (in isoform 2).
                              {ECO:0000303|PubMed:15489334}.
                              /FTId=VSP_002218.
 VAR_SEQ    1254   1254       Missing (in isoform 3).
                              {ECO:0000303|PubMed:15489334}.
                              /FTId=VSP_034600.
 VARIANT     236    236       N -> S (in dbSNP:rs2271075).
                              /FTId=VAR_014284.
 VARIANT     506    506       P -> S (in dbSNP:rs17852587).
                              {ECO:0000269|PubMed:15489334}.
                              /FTId=VAR_031281.
 VARIANT     824    824       A -> G (in dbSNP:rs2691551).
                              /FTId=VAR_014286.
 VARIANT     824    824       A -> P (in dbSNP:rs2814054).
                              /FTId=VAR_014285.
 MUTAGEN     729    731       CDC->LDP: Abolishes methyltransferase
                              activity. {ECO:0000269|PubMed:11959841}.
 MUTAGEN     976    976       T->A: Abrogates interaction with CHD7,
                              NLK and PPARG. Reduces phosphorylation by
                              NLK. Reduces transcriptional repression.
                              {ECO:0000269|PubMed:17952062}.
 MUTAGEN    1224   1224       H->K: Abolishes methyltransferase
                              activity. {ECO:0000269|PubMed:11959841}.
 MUTAGEN    1226   1226       C->A: Abolishes methyltransferase
                              activity. {ECO:0000269|PubMed:11959841}.
 MUTAGEN    1279   1279       C->Y: Abolishes methyltransferase
                              activity. {ECO:0000269|PubMed:11959841}.
 STRAND      191    195       {ECO:0000244|PDB:6BHD}.
 STRAND      203    207       {ECO:0000244|PDB:6BHD}.
 STRAND      213    224       {ECO:0000244|PDB:6BHD}.
 STRAND      227    237       {ECO:0000244|PDB:6BHD}.
 STRAND      239    242       {ECO:0000244|PDB:6BHD}.
 HELIX       244    246       {ECO:0000244|PDB:6BHD}.
 STRAND      247    251       {ECO:0000244|PDB:6BHD}.
 HELIX       255    257       {ECO:0000244|PDB:6BHE}.
 STRAND      263    269       {ECO:0000244|PDB:6BHD}.
 STRAND      274    283       {ECO:0000244|PDB:6BHD}.
 TURN        287    290       {ECO:0000244|PDB:6BHD}.
 STRAND      293    297       {ECO:0000244|PDB:6BHD}.
 STRAND      302    305       {ECO:0000244|PDB:6BHD}.
 HELIX       307    309       {ECO:0000244|PDB:6BHD}.
 STRAND      310    315       {ECO:0000244|PDB:6BHD}.
 HELIX       320    323       {ECO:0000244|PDB:6BHD}.
 HELIX       327    339       {ECO:0000244|PDB:6BHD}.
 STRAND      353    358       {ECO:0000244|PDB:6BHD}.
 STRAND      361    371       {ECO:0000244|PDB:6BHD}.
 STRAND      374    379       {ECO:0000244|PDB:6BHD}.
 TURN        380    383       {ECO:0000244|PDB:6BHD}.
 STRAND      384    389       {ECO:0000244|PDB:6BHD}.
 HELIX       396    403       {ECO:0000244|PDB:6BHD}.
 STRAND     1167   1172       {ECO:0000244|PDB:4X3S}.
 SEQUENCE   1291 AA;  143157 MW;  D8841B4C41B911C5 CRC64;
 MSSLPGCIGL DAATATVESE EIAELQQAVV EELGISMEEL RHFIDEELEK MDCVQQRKKQ
 LAELETWVIQ KESEVAHVDQ LFDDASRAVT NCESLVKDFY SKLGLQYRDS SSEDESSRPT
 EIIEIPDEDD DVLSIDSGDA GSRTPKDQKL REAMAALRKS AQDVQKFMDA VNKKSSSQDL
 HKGTLSQMSG ELSKDGDLIV SMRILGKKRT KTWHKGTLIA IQTVGPGKKY KVKFDNKGKS
 LLSGNHIAYD YHPPADKLYV GSRVVAKYKD GNQVWLYAGI VAETPNVKNK LRFLIFFDDG
 YASYVTQSEL YPICRPLKKT WEDIEDISCR DFIEEYVTAY PNRPMVLLKS GQLIKTEWEG
 TWWKSRVEEV DGSLVRILFL DDKRCEWIYR GSTRLEPMFS MKTSSASALE KKQGQLRTRP
 NMGAVRSKGP VVQYTQDLTG TGTQFKPVEP PQPTAPPAPP FPPAPPLSPQ AGDSDLESQL
 AQSRKQVAKK STSFRPGSVG SGHSSPTSPA LSENVSGGKP GINQTYRSPL GSTASAPAPS
 ALPAPPAPPV FHGMLERAPA EPSYRAPMEK LFYLPHVCSY TCLSRVRPMR NEQYRGKNPL
 LVPLLYDFRR MTARRRVNRK MGFHVIYKTP CGLCLRTMQE IERYLFETGC DFLFLEMFCL
 DPYVLVDRKF QPYKPFYYIL DITYGKEDVP LSCVNEIDTT PPPQVAYSKE RIPGKGVFIN
 TGPEFLVGCD CKDGCRDKSK CACHQLTIQA TACTPGGQIN PNSGYQYKRL EECLPTGVYE
 CNKRCKCDPN MCTNRLVQHG LQVRLQLFKT QNKGWGIRCL DDIAKGSFVC IYAGKILTDD
 FADKEGLEMG DEYFANLDHI ESVENFKEGY ESDAPCSSDS SGVDLKDQED GNSGTEDPEE
 SNDDSSDDNF CKDEDFSTSS VWRSYATRRQ TRGQKENGLS ETTSKDSHPP DLGPPHIPVP
 PSIPVGGCNP PSSEETPKNK VASWLSCNSV SEGGFADSDS HSSFKTNEGG EGRAGGSRME
 AEKASTSGLG IKDEGDIKQA KKEDTDDRNK MSVVTESSRN YGYNPSPVKP EGLRRPPSKT
 SMHQSRRLMA SAQSNPDDVL TLSSSTESEG ESGTSRKPTA GQTSATAVDS DDIQTISSGS
 EGDDFEDKKN MTGPMKRQVA VKSTRGFALK STHGIAIKST NMASVDKGES APVRKNTRQF
 YDGEESCYII DAKLEGNLGR YLNHSCSPNL FVQNVFVDTH DLRFPWVAFF ASKRIRAGTE
 LTWDYNYEVG SVEGKELLCC CGAIECRGRL L

Related products :