SETB1_MOUSE
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 03-AUG-2022, entry version 177.
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).
CC {ECO:0000250|UniProtKB:Q15047, ECO:0000269|PubMed:11791185,
CC ECO:0000269|PubMed:12398767, ECO:0000269|PubMed:29728365,
CC 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}.
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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 iPTMnet; O88974; -.
DR PhosphoSitePlus; O88974; -.
DR EPD; O88974; -.
DR MaxQB; O88974; -.
DR PaxDb; O88974; -.
DR PeptideAtlas; O88974; -.
DR PRIDE; 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 UCSC; uc008qjo.2; mouse. [O88974-5]
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 methyltransferase activity (H3-K9 specific); IDA:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
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:0051567; P:histone H3-K9 methylation; IBA:GO_Central.
DR GO; GO:0036124; P:histone H3-K9 trimethylation; IMP:MGI.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IMP:MGI.
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 assembly; IMP:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR Gene3D; 2.170.270.10; -; 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; IPR002999; Tudor.
DR InterPro; IPR041292; Tudor_4.
DR InterPro; IPR041291; TUDOR_5.
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; SSF54171; 1.
DR SUPFAM; SSF82199; SSF82199; 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
