ID SETB1_MOUSE Reviewed; 1307 AA. AC O88974; Q6AXH8; Q78N64; Q78N65; Q80U84; Q8BTV6; Q8CIX7; Q922K1; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 24-JAN-2024, entry version 184. DE RecName: Full=Histone-lysine N-methyltransferase SETDB1 {ECO:0000305}; DE EC=2.1.1.366 {ECO:0000269|PubMed:11791185, ECO:0000269|PubMed:22939622}; DE AltName: Full=ERG-associated protein with SET domain; DE Short=ESET {ECO:0000303|PubMed:20164836}; DE AltName: Full=SET domain bifurcated 1; GN Name=Setdb1 {ECO:0000312|MGI:MGI:1934229}; GN Synonyms=Eset {ECO:0000303|PubMed:20164836}, Kiaa0067; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ENZYME ACTIVITY, INTERACTION RP WITH ERG, MUTAGENESIS OF CYS-798 AND CYS-1242, AND FUNCTION. RC STRAIN=BDF1; TISSUE=Blood; RX PubMed=11791185; DOI=10.1038/sj.onc.1204998; RA Yang L., Xia L., Wu D.Y., Wang H., Chansky H.A., Schubach W.H., RA Hickstein D.D., Zhang Y.; RT "Molecular cloning of ESET, a novel histone H3-specific methyltransferase RT that interacts with ERG transcription factor."; RL Oncogene 21:148-152(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), NUCLEOTIDE SEQUENCE [GENOMIC DNA], RP ALTERNATIVE SPLICING (ISOFORM 6), AND TISSUE SPECIFICITY. RC STRAIN=BDF1, and C57BL/6J X DBA/2; RX PubMed=14522075; DOI=10.1016/s0167-4781(03)00155-6; RA Blackburn M.L., Chansky H.A., Zielinska-Kwiatkowska A., Matsui Y., Yang L.; RT "Genomic structure and expression of the mouse ESET gene encoding an ERG- RT associated histone methyltransferase with a SET domain."; RL Biochim. Biophys. Acta 1629:8-14(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 7). RC STRAIN=C57BL/6J; TISSUE=Brain; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 145-1307 (ISOFORM 4). RC TISSUE=Brain; RX PubMed=12693553; DOI=10.1093/dnares/10.1.35; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., RA Nakajima D., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II. RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:35-48(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 289-1307 (ISOFORM 4). RC STRAIN=NOD; TISSUE=Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [6] RP INTERACTION WITH HDAC1; HDAC2; SIN3A AND SIN3B. RX PubMed=12398767; DOI=10.1042/bj20020854; RA Yang L., Mei Q., Zielinska-Kwiatkowska A., Matsui Y., Blackburn M.L., RA Benedetti D., Krumm A.A., Taborsky G.J. Jr., Chansky H.A.; RT "An ERG (ets-related gene)-associated histone methyltransferase interacts RT with histone deacetylases 1/2 and transcription co-repressors mSin3A/B."; RL Biochem. J. 369:651-657(2003). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112; SER-117 AND THR-120, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung, Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP FUNCTION, AND MUTAGENESIS OF CYS-1242. RX PubMed=20164836; DOI=10.1038/nature08858; RA Matsui T., Leung D., Miyashita H., Maksakova I.A., Miyachi H., Kimura H., RA Tachibana M., Lorincz M.C., Shinkai Y.; RT "Proviral silencing in embryonic stem cells requires the histone RT methyltransferase ESET."; RL Nature 464:927-931(2010). RN [9] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22939622; DOI=10.1016/j.cell.2012.06.048; RA Pinheiro I., Margueron R., Shukeir N., Eisold M., Fritzsch C., RA Richter F.M., Mittler G., Genoud C., Goyama S., Kurokawa M., Son J., RA Reinberg D., Lachner M., Jenuwein T.; RT "Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian RT heterochromatin integrity."; RL Cell 150:948-960(2012). RN [10] RP FUNCTION, INTERACTION WITH RESF1, AND SUBCELLULAR LOCATION. RX PubMed=29728365; DOI=10.1101/gr.227280.117; RA Fukuda K., Okuda A., Yusa K., Shinkai Y.; RT "A CRISPR knockout screen identifies SETDB1-target retroelement silencing RT factors in embryonic stem cells."; RL Genome Res. 28:846-858(2018). RN [11] RP INTERACTION WITH TASOR, AND TISSUE SPECIFICITY. RX PubMed=31112734; DOI=10.1016/j.yexcr.2019.05.018; RA Gresakova V., Novosadova V., Prochazkova M., Bhargava S., Jenickova I., RA Prochazka J., Sedlacek R.; RT "Fam208a orchestrates interaction protein network essential for early RT embryonic development and cell division."; RL Exp. Cell Res. 382:111437-111437(2019). CC -!- FUNCTION: Histone methyltransferase that specifically trimethylates CC 'Lys-9' of histone H3 (PubMed:11791185, PubMed:22939622). H3 'Lys-9' CC trimethylation represents a specific tag for epigenetic transcriptional CC repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to CC methylated histones. Mainly functions in euchromatin regions, thereby CC playing a central role in the silencing of euchromatic genes. H3 'Lys- CC 9' trimethylation is coordinated with DNA methylation. Probably forms a CC complex with MBD1 and ATF7IP that represses transcription and couples CC DNA methylation and histone 'Lys-9' trimethylation. Its activity is CC dependent on MBD1 and is heritably maintained through DNA replication CC by being recruited by CAF-1. SETDB1 is targeted to histone H3 by CC TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably CC forms a corepressor complex required for activated KRAS-mediated CC promoter hypermethylation and transcriptional silencing of tumor CC suppressor genes (TSGs) or other tumor-related genes in colorectal CC cancer (CRC) cells (By similarity). Required to maintain a CC transcriptionally repressive state of genes in undifferentiated CC embryonic stem cells (ESCs) (By similarity). In ESCs, in collaboration CC with TRIM28, is also required for H3K9me3 and silencing of endogenous CC and introduced retroviruses in a DNA-methylation independent-pathway CC (PubMed:20164836, PubMed:29728365). Associates at promoter regions of CC tumor suppressor genes (TSGs) leading to their gene silencing. The CC SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the CC 3'-exons of zinc-finger coding genes with atypical chromatin signatures CC to establish or maintain/protect H3K9me3 at these transcriptionally CC active regions (By similarity). {ECO:0000250|UniProtKB:Q15047, CC ECO:0000269|PubMed:11791185, ECO:0000269|PubMed:20164836, CC ECO:0000269|PubMed:22939622, ECO:0000269|PubMed:29728365}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L- CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA- CC COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, CC ChEBI:CHEBI:61976; EC=2.1.1.366; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00906, ECO:0000269|PubMed:11791185, CC ECO:0000269|PubMed:22939622}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60289; CC Evidence={ECO:0000269|PubMed:11791185, ECO:0000269|PubMed:22939622}; CC -!- SUBUNIT: Part of a complex containing at least CDYL, REST, WIZ, SETDB1, CC EHMT1 and EHMT2. Forms a complex with ATRX, TRIM28 and ZNF274 (By CC similarity). Probably part of a corepressor complex containing ZNF304, CC TRIM28, SETDB1 and DNMT1. Interacts with TRIM28/TIF1B. Interacts with CC ATF7IP and ATF7IP2; the interaction with ATF7IP is required to CC stimulate histone methyltransferase activity and facilitate the CC conversion of dimethylated to trimethylated H3 'Lys-9'. Interacts with CC MBD1; interaction is abolished when MBD1 is sumoylated. Interacts with CC CBX1 and CBX5. Interacts with DNMT3A and DNMT3B. Interacts with SUMO2. CC Interacts with MPHOSPH8 (By similarity). Interacts with ERG CC (PubMed:11791185). Interacts with HDAC1, HDAC2, SIN3A, SIN3B CC (PubMed:12398767). Interacts with ATRX. Interacts with RESF1 CC (PubMed:29728365). Interacts with ZNF638 (By similarity). Interacts CC with TASOR (PubMed:31112734). Interacts with ZNF263; recruited to the CC SIX3 promoter along with other proteins involved in chromatin CC modification and transcriptional corepression where it contributes to CC transcriptional repression (By similarity). Interacts with PHF13; the CC interaction probably enhances SETDB1 chromatin-associated levels and CC activity (By similarity). {ECO:0000250|UniProtKB:Q15047, CC ECO:0000269|PubMed:11791185, ECO:0000269|PubMed:12398767, CC ECO:0000269|PubMed:29728365, ECO:0000269|PubMed:31112734}. CC -!- INTERACTION: CC O88974; P81270: Erg; NbExp=3; IntAct=EBI-79658, EBI-79647; CC O88974; E9Q5K9: Ythdc1; NbExp=2; IntAct=EBI-79658, EBI-647644; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29728365}. Chromosome CC {ECO:0000269|PubMed:29728365}. Note=Associated with non-pericentromeric CC regions of chromatin. {ECO:0000250|UniProtKB:Q15047}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Comment=Experimental confirmation may be lacking for some isoforms.; CC Name=1; CC IsoId=O88974-1; Sequence=Displayed; CC Name=2; CC IsoId=O88974-2; Sequence=VSP_002219, VSP_002220; CC Name=3; CC IsoId=O88974-3; Sequence=VSP_002221; CC Name=4; CC IsoId=O88974-4; Sequence=VSP_024031; CC Name=5; CC IsoId=O88974-5; Sequence=VSP_024032; CC Name=6; CC IsoId=O88974-6; Sequence=VSP_024031, VSP_024032; CC Name=7; CC IsoId=O88974-7; Sequence=VSP_024033; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:14522075). Strong CC expression in liver and testis (PubMed:14522075, PubMed:31112734). CC Expressed in the brain, lungs, kidneys, uterus and seminal vesicles CC (PubMed:31112734). {ECO:0000269|PubMed:14522075, CC ECO:0000269|PubMed:31112734}. CC -!- DOMAIN: The pre-SET, SET and post-SET domains are all required for CC methyltransferase activity. The 347-amino-acid insertion in the SET CC domain has no effect on the catalytic activity. CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are CC arranged in a triangular cluster; some of these Cys residues contribute CC to the binding of two zinc ions within the cluster. {ECO:0000250}. CC -!- PTM: Degraded by the proteasome, shielded by interaction with ATF7IP. CC {ECO:0000250|UniProtKB:Q15047}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. Histone-lysine methyltransferase family. Suvar3-9 CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00906}. 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; AF091628; AAC43039.1; -; mRNA. DR EMBL; AY091600; AAM13922.1; -; mRNA. DR EMBL; AF546078; AAN52358.1; -; mRNA. DR EMBL; AY226577; AAO73535.2; -; Genomic_DNA. DR EMBL; AY226577; AAO73536.2; -; Genomic_DNA. DR EMBL; BC007176; AAH07176.1; -; mRNA. DR EMBL; BC079537; AAH79537.1; -; mRNA. DR EMBL; AK122198; BAC65480.3; -; Transcribed_RNA. DR EMBL; AK088590; BAC40439.1; -; mRNA. DR CCDS; CCDS17613.1; -. [O88974-4] DR CCDS; CCDS50991.1; -. [O88974-1] DR PIR; T17453; T17453. DR AlphaFoldDB; O88974; -. DR SMR; O88974; -. DR IntAct; O88974; 10. DR STRING; 10090.ENSMUSP00000015841; -. DR GlyGen; O88974; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O88974; -. DR PhosphoSitePlus; O88974; -. DR EPD; O88974; -. DR MaxQB; O88974; -. DR PaxDb; 10090-ENSMUSP00000015841; -. DR PeptideAtlas; O88974; -. DR ProteomicsDB; 261162; -. [O88974-1] DR ProteomicsDB; 261163; -. [O88974-2] DR ProteomicsDB; 261164; -. [O88974-3] DR ProteomicsDB; 261165; -. [O88974-4] DR ProteomicsDB; 261166; -. [O88974-5] DR ProteomicsDB; 261167; -. [O88974-6] DR ProteomicsDB; 261168; -. [O88974-7] DR Pumba; O88974; -. DR UCSC; uc008qjo.2; mouse. [O88974-5] DR AGR; MGI:1934229; -. DR MGI; MGI:1934229; Setdb1. DR eggNOG; KOG1141; Eukaryota. DR InParanoid; O88974; -. DR BRENDA; 2.1.1.366; 3474. DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines. DR ChiTaRS; Setdb1; mouse. DR PRO; PR:O88974; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; O88974; Protein. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0046974; F:histone H3K9 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0140948; F:histone H3K9 monomethyltransferase activity; IEA:RHEA. DR GO; GO:0140949; F:histone H3K9 trimethyltransferase activity; ISO:MGI. DR GO; GO:0140947; F:histone H3K9me2 methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0060348; P:bone development; IMP:MGI. DR GO; GO:0070828; P:heterochromatin organization; IBA:GO_Central. DR GO; GO:0001833; P:inner cell mass cell proliferation; IMP:MGI. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0010629; P:negative regulation of gene expression; IBA:GO_Central. DR GO; GO:0045869; P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin formation; IMP:UniProtKB. DR CDD; cd01395; HMT_MBD; 1. DR CDD; cd10517; SET_SETDB1; 1. DR CDD; cd20382; Tudor_SETDB1_rpt1; 1. DR CDD; cd21181; Tudor_SETDB1_rpt2; 1. DR Gene3D; 2.30.30.140; -; 3. DR Gene3D; 2.170.270.10; SET domain; 2. DR InterPro; IPR016177; DNA-bd_dom_sf. DR InterPro; IPR040880; DUF5604. DR InterPro; IPR025796; Hist-Lys_N-MeTrfase_SETDB1. DR InterPro; IPR001739; Methyl_CpG_DNA-bd. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR007728; Pre-SET_dom. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR047232; SETDB1/2-like_MBD. DR InterPro; IPR002999; Tudor. DR InterPro; IPR041292; Tudor_4. DR InterPro; IPR041291; TUDOR_5. DR PANTHER; PTHR46024; HISTONE-LYSINE N-METHYLTRANSFERASE EGGLESS; 1. DR PANTHER; PTHR46024:SF2; HISTONE-LYSINE N-METHYLTRANSFERASE SETDB1; 1. DR Pfam; PF18300; DUF5604; 1. DR Pfam; PF01429; MBD; 1. DR Pfam; PF05033; Pre-SET; 1. DR Pfam; PF00856; SET; 1. DR Pfam; PF18358; Tudor_4; 1. DR Pfam; PF18359; Tudor_5; 1. DR SMART; SM00391; MBD; 1. DR SMART; SM00468; PreSET; 1. DR SMART; SM00317; SET; 1. DR SMART; SM00333; TUDOR; 2. DR SUPFAM; SSF54171; DNA-binding domain; 1. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS50982; MBD; 1. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50867; PRE_SET; 1. DR PROSITE; PS51573; SAM_MT43_SUVAR39_1; 1. DR PROSITE; PS50280; SET; 1. PE 1: Evidence at protein level; KW Alternative splicing; Chromatin regulator; Chromosome; Coiled coil; KW Isopeptide bond; Metal-binding; Methylation; Methyltransferase; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Repressor; KW S-adenosyl-L-methionine; Transcription; Transcription regulation; KW Transferase; Ubl conjugation; Zinc. FT CHAIN 1..1307 FT /note="Histone-lysine N-methyltransferase SETDB1" FT /id="PRO_0000186065" FT DOMAIN 257..320 FT /note="Tudor 1" FT DOMAIN 347..403 FT /note="Tudor 2" FT DOMAIN 611..682 FT /note="MBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338" FT DOMAIN 744..817 FT /note="Pre-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157" FT DOMAIN 820..1282 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 1291..1307 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT REGION 127..148 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 404..424 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 444..512 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 531..570 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 885..1174 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 30..65 FT /evidence="ECO:0000255" FT COMPBIAS 451..467 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 471..512 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 538..566 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 910..927 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 946..962 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 982..1024 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1051..1067 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1095..1156 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 746 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 746 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 748 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 752 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 752 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 758 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 760 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 798 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 798 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 802 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 804 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 809 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 830..832 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 868 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 870 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 1236 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 1239..1240 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 1242 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 1295 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 1297 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 1302 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT MOD_RES 112 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 120 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1042 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT MOD_RES 1186 FT /note="N6,N6,N6-trimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT MOD_RES 1186 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT MOD_RES 1194 FT /note="N6,N6,N6-trimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT MOD_RES 1194 FT /note="N6,N6-dimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 182 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 182 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 1049 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 1049 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 1055 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 1085 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT CROSSLNK 1165 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15047" FT VAR_SEQ 1..807 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_002221" FT VAR_SEQ 474 FT /note="D -> ES (in isoform 4 and isoform 6)" FT /evidence="ECO:0000303|PubMed:12693553, FT ECO:0000303|PubMed:16141072" FT /id="VSP_024031" FT VAR_SEQ 482..486 FT /note="SRKQV -> AQSQK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11791185" FT /id="VSP_002219" FT VAR_SEQ 489..1307 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11791185" FT /id="VSP_002220" FT VAR_SEQ 527..1307 FT /note="Missing (in isoform 5 and isoform 6)" FT /evidence="ECO:0000303|PubMed:14522075" FT /id="VSP_024032" FT VAR_SEQ 756..1307 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024033" FT MUTAGEN 798 FT /note="C->T: Abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:11791185" FT MUTAGEN 1242 FT /note="C->A: Decreases endogenous retroviruses silencing FT and cell growth." FT /evidence="ECO:0000269|PubMed:20164836" FT MUTAGEN 1242 FT /note="C->T: Abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:11791185" FT CONFLICT 463 FT /note="I -> M (in Ref. 5; BAC40439)" FT /evidence="ECO:0000305" FT CONFLICT 1092 FT /note="P -> S (in Ref. 4; BAC65480)" FT /evidence="ECO:0000305" SQ SEQUENCE 1307 AA; 144549 MW; 326AED6371D156C2 CRC64; MSSLPGCMSL AAAPAAADSA EIAELQQAVV EELGISMEEL RQYIDEELEK MDCIQQRKKQ LAELETWVLQ KESEVAYVDR LFDDASREVT NCESLVKDFY SKLGLQYHDS SSEDEASRPT EIIEIPDEDD DVLSIDSGDA GSRTPKDQKL REAMAALRKS AQDVQKFMDA VNKKSSSQDL HKGTLGQVSG ELSKDGDLIV SMRILGKKRT KTWHKGTLIA IQTVGLGKKY KVKFDNKGKS LLSGNHIAYD YHPPADKLFV GSRVVAKYKD GNQVWLYAGI VAETPNVKNK LRFLIFFDDG YASYVTQSEL YPICRPLKKT WEDIEDSSCR DFIEEYITAY PNRPMVLLKS GQLIKTEWEG TWWKSRVEEV DGSLVRILFL DDKRCEWIYR GSTRLEPMFS MKTSSASAME KKQGGQLRTR PNMGAVRSKG PVVQYTQDLT GTGIQFKPME PLQPIAPPAP LPIPPLSPQA ADTDLESQLA QSRKQVAKKS TSFRPGSVGS GHSSPTSSTL SENVSAGKLG INQTYRSPLA SVTSTPASAA PPVPPVPPGP PTPPGPPAPP GPLAPPAFHG MLERAPAEPS YRAPMEKLFY LPHVCSYTCL SRIRPMRNEQ YRGKNPLLVP LLYDFRRMTA RRRVNRKMGF HVIYKTPCGL CLRTMQEIER YLFETGCDFL FLEMFCLDPY VLVDRKFQPF KPFYYILDIT YGKEDVPLSC VNEIDTTPPP QVAYSKERIP GKGVFINTGP EFLVGCDCKD GCRDKSKCAC HQLTIQATAC TPGGQVNPNS GYQYKRLEEC LPTGVYECNK RCNCDPNMCT NRLVQHGLQV RLQLFKTQNK GWGIRCLDDI AKGSFVCIYA GKILTDDFAD KEGLEMGDEY FANLDHIESV ENFKEGYESD VPTSSDSSGV DMKDQEDGNS GSEDPEESND DSSDDNFCKD EDFSTSSVWR SYATRRQTRG QKENELSEMT SKDSRPPDLG PPHVPIPSSV SVGGCNPPSS EETPKNKVAS WLSCNSVSEG GFADSDSRSS FKTSEGGDGR AGGGRGEAER ASTSGLSFKD EGDNKQPKKE DPENRNKMPV VTEGSQNHGH NPPMKSEGLR RPASKMSVLQ SQRVVTSTQS NPDDILTLSS STESEGESGT SRKPTAGHTS ATAVDSDDIQ TISSGSDGDD FEDKKNLSGP TKRQVAVKST RGFALKSTHG IAIKSTNMAS VDKGESAPVR KNTRQFYDGE ESCYIIDAKL EGNLGRYLNH SCSPNLFVQN VFVDTHDLRF PWVAFFASKR IRAGTELTWD YNYEVGSVEG KELLCCCGAI ECRGRLL //