SETB1_HUMAN
ID SETB1_HUMAN Reviewed; 1291 AA.
AC Q15047; A6NEW2; Q5SZD8; Q5SZD9; Q5SZE0; Q5SZE7; Q96GM9;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Histone-lysine N-methyltransferase SETDB1 {ECO:0000305};
DE EC=2.1.1.366 {ECO:0000269|PubMed:14536086};
DE AltName: Full=ERG-associated protein with SET domain;
DE Short=ESET {ECO:0000303|PubMed:14536086};
DE AltName: Full=Histone H3-K9 methyltransferase 4;
DE Short=H3-K9-HMTase 4;
DE AltName: Full=Lysine N-methyltransferase 1E;
DE AltName: Full=SET domain bifurcated 1;
GN Name=SETDB1 {ECO:0000312|HGNC:HGNC:10761};
GN Synonyms=ESET {ECO:0000303|PubMed:14536086}, KIAA0067, KMT1E;
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 MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP SER-506.
RC TISSUE=Muscle, and Uterus;
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 [5]
RP CHARACTERIZATION, MUTAGENESIS OF 729-CYS--CYS-731; HIS-1224; CYS-1226 AND
RP CYS-1279, AND INTERACTION WITH TRIM28.
RX PubMed=11959841; DOI=10.1101/gad.973302;
RA Schultz D.C., Ayyanathan K., Negorev D., Maul G.G., Rauscher F.J. III;
RT "SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific
RT methyltransferase that contributes to HP1-mediated silencing of euchromatic
RT genes by KRAB zinc-finger proteins.";
RL Genes Dev. 16:919-932(2002).
RN [6]
RP FUNCTION.
RX PubMed=12869583; DOI=10.1101/gad.1102803;
RA Ayyanathan K., Lechner M.S., Bell P., Maul G.G., Schultz D.C., Yamada Y.,
RA Tanaka K., Torigoe K., Rauscher F.J. III;
RT "Regulated recruitment of HP1 to a euchromatic gene induces mitotically
RT heritable, epigenetic gene silencing: a mammalian cell culture model of
RT gene variegation.";
RL Genes Dev. 17:1855-1869(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH ATF7IP,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY.
RX PubMed=14536086; DOI=10.1016/j.molcel.2003.08.007;
RA Wang H., An W., Cao R., Xia L., Erdjument-Bromage H., Chatton B.,
RA Tempst P., Roeder R.G., Zhang Y.;
RT "mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of
RT histone H3 to cause transcriptional repression.";
RL Mol. Cell 12:475-487(2003).
RN [8]
RP RETRACTED PAPER.
RX PubMed=15327775; DOI=10.1016/j.molcel.2004.06.043;
RA Sarraf S.A., Stancheva I.;
RT "Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9
RT by SETDB1 to DNA replication and chromatin assembly.";
RL Mol. Cell 15:595-605(2004).
RN [9]
RP RETRACTION NOTICE OF PUBMED:15327775.
RX PubMed=30849389; DOI=10.1016/j.molcel.2019.02.023;
RA Sarraf S.A., Stancheva I.;
RT "Retraction Notice to: Methyl-CpG Binding Protein MBD1 Couples Histone H3
RT Methylation at Lysine 9 by SETDB1 to DNA Replication and Chromatin
RT Assembly.";
RL Mol. Cell 73:1084-1084(2019).
RN [10]
RP INTERACTION WITH CBX1 AND CBX5.
RX PubMed=15899859; DOI=10.1128/mcb.25.11.4552-4564.2005;
RA Verschure P.J., van der Kraan I., de Leeuw W., van der Vlag J.,
RA Carpenter A.E., Belmont A.S., van Driel R.;
RT "In vivo HP1 targeting causes large-scale chromatin condensation and
RT enhanced histone lysine methylation.";
RL Mol. Cell. Biol. 25:4552-4564(2005).
RN [11]
RP RETRACTED PAPER.
RX PubMed=17066076; DOI=10.1038/sj.emboj.7601404;
RA Lyst M.J., Nan X., Stancheva I.;
RT "Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS
RT proteins.";
RL EMBO J. 25:5317-5328(2006).
RN [12]
RP RETRACTION NOTICE OF PUBMED:17066076.
RX PubMed=31612521; DOI=10.15252/embj.2019103220;
RA Lyst M.J., Nan X., Stancheva I.;
RT "Retraction: Regulation of MBD1-mediated transcriptional repression by SUMO
RT and PIAS proteins.";
RL EMBO J. 38:e103220-e103220(2019).
RN [13]
RP INTERACTION WITH ATF7IP AND ATF7IP2.
RX PubMed=15691849; DOI=10.1074/jbc.m413654200;
RA Ichimura T., Watanabe S., Sakamoto Y., Aoto T., Fujita N., Nakao M.;
RT "Transcriptional repression and heterochromatin formation by MBD1 and
RT MCAF/AM family proteins.";
RL J. Biol. Chem. 280:13928-13935(2005).
RN [14]
RP INTERACTION WITH DNMT3A AND DNMT3B.
RX PubMed=16682412; DOI=10.1074/jbc.m513249200;
RA Li H., Rauch T., Chen Z.-X., Szabo P.E., Riggs A.D., Pfeifer G.P.;
RT "The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A
RT interact directly and localize to promoters silenced in cancer cells.";
RL J. Biol. Chem. 281:19489-19500(2006).
RN [15]
RP INTERACTION WITH SUMO2.
RX PubMed=16567619; DOI=10.1073/pnas.0601066103;
RA Rosendorff A., Sakakibara S., Lu S., Kieff E., Xuan Y., DiBacco A., Shi Y.,
RA Shi Y., Gill G.;
RT "NXP-2 association with SUMO-2 depends on lysines required for
RT transcriptional repression.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5308-5313(2006).
RN [16]
RP EXPRESSION IN HUNTINGTON DISEASE.
RX PubMed=17142323; DOI=10.1073/pnas.0606373103;
RA Ryu H., Lee J., Hagerty S.W., Soh B.Y., McAlpin S.E., Cormier K.A.,
RA Smith K.M., Ferrante R.J.;
RT "ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in
RT Huntington's disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:19176-19181(2006).
RN [17]
RP RETRACTED PAPER.
RX PubMed=17952062; DOI=10.1038/ncb1647;
RA Takada I., Mihara M., Suzawa M., Ohtake F., Kobayashi S., Igarashi M.,
RA Youn M.Y., Takeyama K., Nakamura T., Mezaki Y., Takezawa S., Yogiashi Y.,
RA Kitagawa H., Yamada G., Takada S., Minami Y., Shibuya H., Matsumoto K.,
RA Kato S.;
RT "A histone lysine methyltransferase activated by non-canonical Wnt
RT signalling suppresses PPAR-gamma transactivation.";
RL Nat. Cell Biol. 9:1273-1285(2007).
RN [18]
RP RETRACTION NOTICE OF PUBMED:17952062.
RX PubMed=25358353; DOI=10.1038/ncb3069;
RA Takada I., Mihara M., Suzawa M., Ohtake F., Kobayashi S., Igarashi M.,
RA Youn M.Y., Takeyama K., Nakamura T., Mezaki Y., Takezawa S., Yogiashi Y.,
RA Kitagawa H., Yamada G., Takada S., Minami Y., Shibuya H., Matsumoto K.,
RA Kato S.;
RL Nat. Cell Biol. 16:1126-1126(2014).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1066, 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 [20]
RP IDENTIFICATION IN A COMPLEX WITH REST; CDYL; WIZ; EHMT1 AND EHMT2.
RX PubMed=19061646; DOI=10.1016/j.molcel.2008.10.025;
RA Mulligan P., Westbrook T.F., Ottinger M., Pavlova N., Chang B., Macia E.,
RA Shi Y.J., Barretina J., Liu J., Howley P.M., Elledge S.J., Shi Y.;
RT "CDYL bridges REST and histone methyltransferases for gene repression and
RT suppression of cellular transformation.";
RL Mol. Cell 32:718-726(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1066, 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 [22]
RP INTERACTION WITH MPHOSPH8.
RX PubMed=20871592; DOI=10.1038/emboj.2010.239;
RA Kokura K., Sun L., Bedford M.T., Fang J.;
RT "Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and
RT promotes tumour cell motility and invasion.";
RL EMBO J. 29:3673-3687(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1066, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [25]
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1025 AND SER-1066, AND
RP 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 [27]
RP FUNCTION, POSSIBLE IDENTIFICATION IN A COREPRESSOR COMPLEX, AND
RP CHROMATIN-BINDING.
RX PubMed=24623306; DOI=10.7554/elife.02313;
RA Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
RT "A KRAS-directed transcriptional silencing pathway that mediates the CpG
RT island methylator phenotype.";
RL Elife 3:E02313-E02313(2014).
RN [28]
RP 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 [29]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-1170 AND LYS-1178, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032 AND LYS-1069, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [31]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [32]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032 AND LYS-1069, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [33]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032 AND LYS-1069, AND
RP IDENTIFICATION BY MASS 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 [34]
RP FUNCTION, INTERACTION WITH ATRX, AND FORMATION OF A COMPLEX WITH ATRX;
RP TRIM28 AND ZNF274.
RX PubMed=27029610; DOI=10.1080/15592294.2016.1169351;
RA Valle-Garcia D., Qadeer Z.A., McHugh D.S., Ghiraldini F.G., Chowdhury A.H.,
RA Hasson D., Dyer M.A., Recillas-Targa F., Bernstein E.;
RT "ATRX binds to atypical chromatin domains at the 3' exons of zinc finger
RT genes to preserve H3K9me3 enrichment.";
RL Epigenetics 11:398-414(2016).
RN [35]
RP FUNCTION, INTERACTION WITH ATF7IP, DEGRADATION, AND SUBCELLULAR LOCATION.
RX PubMed=27732843; DOI=10.1016/j.celrep.2016.09.050;
RA Timms R.T., Tchasovnikarova I.A., Antrobus R., Dougan G., Lehner P.J.;
RT "ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is
RT Essential for Heterochromatin Formation by the HUSH Complex.";
RL Cell Rep. 17:653-659(2016).
RN [36]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-182; LYS-1032; LYS-1038; LYS-1069
RP AND LYS-1149, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [37]
RP INTERACTION WITH ZNF638.
RX PubMed=30487602; DOI=10.1038/s41586-018-0750-6;
RA Zhu Y., Wang G.Z., Cingoez O., Goff S.P.;
RT "NP220 mediates silencing of unintegrated retroviral DNA.";
RL Nature 564:278-282(2018).
RN [38]
RP INTERACTION WITH ZNF263.
RX PubMed=32051553; DOI=10.1038/s41388-020-1206-7;
RA Yu Z., Feng J., Wang W., Deng Z., Zhang Y., Xiao L., Wang Z., Liu C.,
RA Liu Q., Chen S., Wu M.;
RT "The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma
RT epigenetically.";
RL Oncogene 39:3163-3178(2020).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 196-402.
RG Structural genomics consortium (SGC);
RT "The crystal structure of Tudor domain of human histone-lysine N-
RT methyltransferase SETDB1.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Histone methyltransferase that specifically trimethylates
CC 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific
CC tag for epigenetic transcriptional repression by recruiting HP1 (CBX1,
CC CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in
CC euchromatin regions, thereby playing a central role in the silencing of
CC euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA
CC methylation (PubMed:12869583). Required for HUSH-mediated
CC heterochromatin formation and gene silencing. Forms a complex with MBD1
CC and ATF7IP that represses transcription and couples DNA methylation and
CC histone 'Lys-9' trimethylation (PubMed:27732843, PubMed:14536086). Its
CC activity is dependent on MBD1 and is heritably maintained through DNA
CC replication by being recruited by CAF-1 (PubMed:14536086,). SETDB1 is
CC targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB
CC zinc-finger proteins. Probably forms a corepressor complex required for
CC activated KRAS-mediated promoter hypermethylation and transcriptional
CC silencing of tumor suppressor genes (TSGs) or other tumor-related genes
CC in colorectal cancer (CRC) cells (PubMed:24623306). Required to
CC maintain a transcriptionally repressive state of genes in
CC undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In
CC ESCs, in collaboration with TRIM28, is also required for H3K9me3 and
CC silencing of endogenous and introduced retroviruses in a DNA-
CC methylation independent-pathway (By similarity). Associates at promoter
CC regions of tumor suppressor genes (TSGs) leading to their gene
CC silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play
CC a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes
CC with atypical chromatin signatures to establish or maintain/protect
CC H3K9me3 at these transcriptionally active regions (PubMed:27029610).
CC {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:12869583,
CC ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306,
CC ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27732843}.
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:14536086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60289;
CC Evidence={ECO:0000269|PubMed:14536086};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.78 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:14536086};
CC -!- SUBUNIT: Part of a complex containing at least CDYL, REST, WIZ, SETDB1,
CC EHMT1 and EHMT2 (PubMed:19061646). Forms a complex with ATRX, TRIM28
CC and ZNF274 (PubMed:27029610). Probably part of a corepressor complex
CC containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306).
CC Interacts with TRIM28/TIF1B (PubMed:11959841). Interacts with ATF7IP
CC and ATF7IP2; the interaction with ATF7IP protects SETDB1 from
CC proteasomal degradation and is required to stimulate histone
CC methyltransferase activity and facilitate the conversion of
CC dimethylated to trimethylated H3 'Lys-9' (PubMed:14536086,
CC PubMed:15691849). Interacts with CBX1 and CBX5 (PubMed:15899859).
CC Interacts with DNMT3A and DNMT3B (PubMed:16682412). Interacts with
CC SUMO2. Interacts with MPHOSPH8 (PubMed:20871592). Interacts with ERG
CC (By similarity). Interacts with HDAC1, HDAC2, SIN3A and SIN3B (By
CC similarity). Interacts with ATRX. Interacts with RESF1 (By similarity).
CC Interacts with ZNF638 (PubMed:30487602). Interacts with TASOR (By
CC similarity). Interacts with ZNF263; recruited to the SIX3 promoter
CC along with other proteins involved in chromatin modification and
CC transcriptional corepression where it contributes to transcriptional
CC repression (PubMed:32051553). {ECO:0000250|UniProtKB:O88974,
CC ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:14536086,
CC ECO:0000269|PubMed:15327775, ECO:0000269|PubMed:15691849,
CC ECO:0000269|PubMed:15899859, ECO:0000269|PubMed:16567619,
CC ECO:0000269|PubMed:16682412, ECO:0000269|PubMed:17066076,
CC ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:20871592,
CC ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610,
CC ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:32051553}.
CC -!- INTERACTION:
CC Q15047; P31749: AKT1; NbExp=9; IntAct=EBI-79691, EBI-296087;
CC Q15047; Q6P1J9: CDC73; NbExp=3; IntAct=EBI-79691, EBI-930143;
CC Q15047; Q9Y6K1: DNMT3A; NbExp=7; IntAct=EBI-79691, EBI-923653;
CC Q15047; Q9UIS9: MBD1; NbExp=3; IntAct=EBI-79691, EBI-867196;
CC Q15047; Q99549: MPHOSPH8; NbExp=3; IntAct=EBI-79691, EBI-2653928;
CC Q15047-2; Q15027: ACAP1; NbExp=3; IntAct=EBI-9090795, EBI-751746;
CC Q15047-2; Q9NPJ3: ACOT13; NbExp=3; IntAct=EBI-9090795, EBI-1045357;
CC Q15047-2; Q8IWZ3-3: ANKHD1; NbExp=3; IntAct=EBI-9090795, EBI-25833200;
CC Q15047-2; O43307: ARHGEF9; NbExp=3; IntAct=EBI-9090795, EBI-3447299;
CC Q15047-2; Q66PJ3-4: ARL6IP4; NbExp=3; IntAct=EBI-9090795, EBI-5280499;
CC Q15047-2; Q9Y576: ASB1; NbExp=3; IntAct=EBI-9090795, EBI-2323092;
CC Q15047-2; Q14032: BAAT; NbExp=3; IntAct=EBI-9090795, EBI-8994378;
CC Q15047-2; Q13072: BAGE; NbExp=3; IntAct=EBI-9090795, EBI-25884811;
CC Q15047-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-9090795, EBI-11524452;
CC Q15047-2; Q6PH81: C16orf87; NbExp=3; IntAct=EBI-9090795, EBI-6598617;
CC Q15047-2; Q96HJ3-2: CCDC34; NbExp=3; IntAct=EBI-9090795, EBI-17641690;
CC Q15047-2; Q96A33: CCDC47; NbExp=3; IntAct=EBI-9090795, EBI-720151;
CC Q15047-2; Q96LY2-2: CCDC74B; NbExp=3; IntAct=EBI-9090795, EBI-17967022;
CC Q15047-2; Q9GZT6: CCDC90B; NbExp=3; IntAct=EBI-9090795, EBI-713148;
CC Q15047-2; Q7Z7K6: CENPV; NbExp=3; IntAct=EBI-9090795, EBI-1210604;
CC Q15047-2; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-9090795, EBI-742887;
CC Q15047-2; Q9NX63: CHCHD3; NbExp=3; IntAct=EBI-9090795, EBI-743375;
CC Q15047-2; Q99828: CIB1; NbExp=3; IntAct=EBI-9090795, EBI-372594;
CC Q15047-2; P15169: CPN1; NbExp=3; IntAct=EBI-9090795, EBI-2116369;
CC Q15047-2; P43234: CTSO; NbExp=3; IntAct=EBI-9090795, EBI-2874283;
CC Q15047-2; O95424: DEXI; NbExp=3; IntAct=EBI-9090795, EBI-724515;
CC Q15047-2; O43598: DNPH1; NbExp=3; IntAct=EBI-9090795, EBI-748674;
CC Q15047-2; P21728: DRD1; NbExp=3; IntAct=EBI-9090795, EBI-6624459;
CC Q15047-2; P60228: EIF3E; NbExp=3; IntAct=EBI-9090795, EBI-347740;
CC Q15047-2; Q96J88-3: EPSTI1; NbExp=3; IntAct=EBI-9090795, EBI-25885343;
CC Q15047-2; Q8IVH2-2: FOXP4; NbExp=3; IntAct=EBI-9090795, EBI-25885364;
CC Q15047-2; Q96NE9-2: FRMD6; NbExp=3; IntAct=EBI-9090795, EBI-13213391;
CC Q15047-2; O14926: FSCN2; NbExp=3; IntAct=EBI-9090795, EBI-21017948;
CC Q15047-2; Q06547-2: GABPB1; NbExp=3; IntAct=EBI-9090795, EBI-618189;
CC Q15047-2; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-9090795, EBI-9088619;
CC Q15047-2; P19440-3: GGT1; NbExp=3; IntAct=EBI-9090795, EBI-21558069;
CC Q15047-2; O95837: GNA14; NbExp=3; IntAct=EBI-9090795, EBI-7951023;
CC Q15047-2; Q96F32: GNB5; NbExp=3; IntAct=EBI-9090795, EBI-25902214;
CC Q15047-2; O43292-2: GPAA1; NbExp=3; IntAct=EBI-9090795, EBI-25884370;
CC Q15047-2; Q9NWQ4-1: GPATCH2L; NbExp=3; IntAct=EBI-9090795, EBI-11959863;
CC Q15047-2; Q9UJ42: GPR160; NbExp=3; IntAct=EBI-9090795, EBI-25885139;
CC Q15047-2; Q96D09: GPRASP2; NbExp=3; IntAct=EBI-9090795, EBI-473189;
CC Q15047-2; Q13322-4: GRB10; NbExp=3; IntAct=EBI-9090795, EBI-12353035;
CC Q15047-2; P62805: H4C9; NbExp=3; IntAct=EBI-9090795, EBI-302023;
CC Q15047-2; O00165: HAX1; NbExp=3; IntAct=EBI-9090795, EBI-357001;
CC Q15047-2; Q8N7T0: hCG_1820408; NbExp=3; IntAct=EBI-9090795, EBI-25858908;
CC Q15047-2; P52597: HNRNPF; NbExp=3; IntAct=EBI-9090795, EBI-352986;
CC Q15047-2; Q92826: HOXB13; NbExp=3; IntAct=EBI-9090795, EBI-11317274;
CC Q15047-2; P09017: HOXC4; NbExp=3; IntAct=EBI-9090795, EBI-3923226;
CC Q15047-2; Q03933-2: HSF2; NbExp=3; IntAct=EBI-9090795, EBI-10223348;
CC Q15047-2; P42858: HTT; NbExp=15; IntAct=EBI-9090795, EBI-466029;
CC Q15047-2; Q02363: ID2; NbExp=3; IntAct=EBI-9090795, EBI-713450;
CC Q15047-2; Q96FT9-2: IFT43; NbExp=3; IntAct=EBI-9090795, EBI-11944538;
CC Q15047-2; P78318: IGBP1; NbExp=3; IntAct=EBI-9090795, EBI-1055954;
CC Q15047-2; P17936: IGFBP3; NbExp=3; IntAct=EBI-9090795, EBI-715709;
CC Q15047-2; P26951: IL3RA; NbExp=3; IntAct=EBI-9090795, EBI-1757512;
CC Q15047-2; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-9090795, EBI-743960;
CC Q15047-2; Q9Y4X4: KLF12; NbExp=3; IntAct=EBI-9090795, EBI-750750;
CC Q15047-2; Q5JUW0-3: KRBOX4; NbExp=3; IntAct=EBI-9090795, EBI-12893625;
CC Q15047-2; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-9090795, EBI-9996449;
CC Q15047-2; Q9H2C1: LHX5; NbExp=3; IntAct=EBI-9090795, EBI-25835523;
CC Q15047-2; Q9Y234: LIPT1; NbExp=3; IntAct=EBI-9090795, EBI-727376;
CC Q15047-2; P51884: LUM; NbExp=3; IntAct=EBI-9090795, EBI-725780;
CC Q15047-2; Q96GV9: MACIR; NbExp=3; IntAct=EBI-9090795, EBI-2350695;
CC Q15047-2; Q9H213: MAGEH1; NbExp=3; IntAct=EBI-9090795, EBI-473834;
CC Q15047-2; P80192: MAP3K9; NbExp=3; IntAct=EBI-9090795, EBI-3951604;
CC Q15047-2; Q15759: MAPK11; NbExp=3; IntAct=EBI-9090795, EBI-298304;
CC Q15047-2; A0JLT2-2: MED19; NbExp=3; IntAct=EBI-9090795, EBI-13288755;
CC Q15047-2; Q9H8H3: METTL7A; NbExp=3; IntAct=EBI-9090795, EBI-1390168;
CC Q15047-2; P41218: MNDA; NbExp=3; IntAct=EBI-9090795, EBI-2829677;
CC Q15047-2; Q8N983-3: MRPL43; NbExp=3; IntAct=EBI-9090795, EBI-11109389;
CC Q15047-2; Q16718: NDUFA5; NbExp=3; IntAct=EBI-9090795, EBI-746417;
CC Q15047-2; P49821: NDUFV1; NbExp=3; IntAct=EBI-9090795, EBI-748312;
CC Q15047-2; Q2M1J6: OXA1L; NbExp=3; IntAct=EBI-9090795, EBI-9978021;
CC Q15047-2; Q16342: PDCD2; NbExp=3; IntAct=EBI-9090795, EBI-359462;
CC Q15047-2; Q9BRX2: PELO; NbExp=3; IntAct=EBI-9090795, EBI-1043580;
CC Q15047-2; Q9Y6X2: PIAS3; NbExp=3; IntAct=EBI-9090795, EBI-2803703;
CC Q15047-2; Q86T03: PIP4P1; NbExp=3; IntAct=EBI-9090795, EBI-6164623;
CC Q15047-2; Q6P1J6-2: PLB1; NbExp=3; IntAct=EBI-9090795, EBI-10694821;
CC Q15047-2; Q9UNA4: POLI; NbExp=3; IntAct=EBI-9090795, EBI-741774;
CC Q15047-2; P07225: PROS1; NbExp=3; IntAct=EBI-9090795, EBI-2803380;
CC Q15047-2; Q3YEC7-3: RABL6; NbExp=3; IntAct=EBI-9090795, EBI-25885259;
CC Q15047-2; Q96I51: RCC1L; NbExp=3; IntAct=EBI-9090795, EBI-2117080;
CC Q15047-2; O94844: RHOBTB1; NbExp=3; IntAct=EBI-9090795, EBI-6426999;
CC Q15047-2; Q9UJD0: RIMS3; NbExp=3; IntAct=EBI-9090795, EBI-3909436;
CC Q15047-2; Q9NWS8-3: RMND1; NbExp=3; IntAct=EBI-9090795, EBI-25884400;
CC Q15047-2; Q9Y508: RNF114; NbExp=3; IntAct=EBI-9090795, EBI-723587;
CC Q15047-2; Q9ULK6-3: RNF150; NbExp=3; IntAct=EBI-9090795, EBI-23640835;
CC Q15047-2; P62913-2: RPL11; NbExp=3; IntAct=EBI-9090795, EBI-11027771;
CC Q15047-2; P18077: RPL35A; NbExp=3; IntAct=EBI-9090795, EBI-353383;
CC Q15047-2; Q99643: SDHC; NbExp=3; IntAct=EBI-9090795, EBI-1224539;
CC Q15047-2; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-9090795, EBI-745901;
CC Q15047-2; Q01105-2: SET; NbExp=3; IntAct=EBI-9090795, EBI-7481343;
CC Q15047-2; Q13573: SNW1; NbExp=3; IntAct=EBI-9090795, EBI-632715;
CC Q15047-2; Q9Y5X0: SNX10; NbExp=3; IntAct=EBI-9090795, EBI-10329478;
CC Q15047-2; Q8WV41: SNX33; NbExp=3; IntAct=EBI-9090795, EBI-2481535;
CC Q15047-2; P56693: SOX10; NbExp=3; IntAct=EBI-9090795, EBI-1167533;
CC Q15047-2; Q9BRW5: SP2; NbExp=3; IntAct=EBI-9090795, EBI-25868254;
CC Q15047-2; Q13586: STIM1; NbExp=3; IntAct=EBI-9090795, EBI-448878;
CC Q15047-2; Q13033-2: STRN3; NbExp=3; IntAct=EBI-9090795, EBI-1053876;
CC Q15047-2; O43761: SYNGR3; NbExp=3; IntAct=EBI-9090795, EBI-11321949;
CC Q15047-2; P15884: TCF4; NbExp=3; IntAct=EBI-9090795, EBI-533224;
CC Q15047-2; Q92481: TFAP2B; NbExp=3; IntAct=EBI-9090795, EBI-725275;
CC Q15047-2; Q3YBM2: TMEM176B; NbExp=3; IntAct=EBI-9090795, EBI-2821479;
CC Q15047-2; Q969K7: TMEM54; NbExp=3; IntAct=EBI-9090795, EBI-3922833;
CC Q15047-2; P51580: TPMT; NbExp=3; IntAct=EBI-9090795, EBI-25902017;
CC Q15047-2; Q9UJA5: TRMT6; NbExp=3; IntAct=EBI-9090795, EBI-934061;
CC Q15047-2; Q99598: TSNAX; NbExp=3; IntAct=EBI-9090795, EBI-742638;
CC Q15047-2; Q8NB14: USP38; NbExp=3; IntAct=EBI-9090795, EBI-2512509;
CC Q15047-2; Q15836: VAMP3; NbExp=3; IntAct=EBI-9090795, EBI-722343;
CC Q15047-2; O95498: VNN2; NbExp=3; IntAct=EBI-9090795, EBI-21494555;
CC Q15047-2; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-9090795, EBI-12040603;
CC Q15047-2; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-9090795, EBI-14104088;
CC Q15047-2; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-9090795, EBI-524753;
CC Q15047-2; Q9BQ24: ZFYVE21; NbExp=3; IntAct=EBI-9090795, EBI-2849569;
CC Q15047-2; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-9090795, EBI-2602314;
CC Q15047-2; Q14202: ZMYM3; NbExp=3; IntAct=EBI-9090795, EBI-2556139;
CC Q15047-2; Q05CR2: ZNF248; NbExp=3; IntAct=EBI-9090795, EBI-25835471;
CC Q15047-2; Q9UL40: ZNF346; NbExp=3; IntAct=EBI-9090795, EBI-2462313;
CC Q15047-2; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-9090795, EBI-12010736;
CC Q15047-2; O15535: ZSCAN9; NbExp=3; IntAct=EBI-9090795, EBI-751531;
CC Q15047-2; Q9HBH6; NbExp=3; IntAct=EBI-9090795, EBI-25901704;
CC Q15047-3; O75031: HSF2BP; NbExp=3; IntAct=EBI-11149962, EBI-7116203;
CC Q15047-3; Q15654: TRIP6; NbExp=3; IntAct=EBI-11149962, EBI-742327;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27732843}. Cytoplasm
CC {ECO:0000269|PubMed:27732843}. Chromosome. Note=Associated with non-
CC pericentromeric regions of chromatin. Excluded from nucleoli and
CC islands of condensed chromatin. {ECO:0000269|PubMed:27732843}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15047-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15047-2; Sequence=VSP_002217, VSP_002218;
CC Name=3;
CC IsoId=Q15047-3; Sequence=VSP_034600;
CC -!- TISSUE SPECIFICITY: Widely expressed. High expression in testis.
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: Isoform 2 lacks all domains required for histone
CC methyltransferase 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:0000269|PubMed:27732843}.
CC -!- MISCELLANEOUS: Highly up-regulated in Huntington disease patients,
CC suggesting that participates in the altered chromatin modulation and
CC transcription dysfunction observed in Huntington disease. Its down-
CC regulation has salubrious effects on patients, suggesting that it may
CC be a promising treatment in Huntington disease patients.
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 -!- CAUTION: Was reported to be recruited by MBD1, during DNA replication,
CC to form a S phase-specific complex that would facilitate methylation of
CC H3 'Lys-9' during replication-coupled chromatin assembly and would be
CC at least composed of the CAF-1 subunit CHAF1A, MBD1 and SETDB1
CC (PubMed:15327775, PubMed:17066076). However, these papers have been
CC retracted because some data, results and conclusions are not reliable
CC (PubMed:30849389, PubMed:31612521). {ECO:0000269|PubMed:15327775,
CC ECO:0000269|PubMed:17066076, ECO:0000269|PubMed:30849389,
CC ECO:0000269|PubMed:31612521}.
CC -!- CAUTION: Was reported to trimethylate H3 'Lys-9', to interact with
CC CHD7, NLK1 and PPARG and to be phosphorylated at Thr-796
CC (PubMed:17952062). However, this work was later retracted although its
CC role in H3 'Lys-9' trimethylation is supported by other papers
CC (PubMed:25358353). {ECO:0000269|PubMed:17952062,
CC ECO:0000269|PubMed:25358353, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA06689.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D31891; BAA06689.2; ALT_INIT; mRNA.
DR EMBL; AL590133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53506.1; -; Genomic_DNA.
DR EMBL; BC009362; AAH09362.1; -; mRNA.
DR EMBL; BC028671; AAH28671.1; -; mRNA.
DR CCDS; CCDS44217.1; -. [Q15047-1]
DR CCDS; CCDS58026.1; -. [Q15047-2]
DR CCDS; CCDS972.1; -. [Q15047-3]
DR RefSeq; NP_001138887.1; NM_001145415.1. [Q15047-1]
DR RefSeq; NP_001230420.1; NM_001243491.1. [Q15047-2]
DR RefSeq; NP_036564.3; NM_012432.3. [Q15047-3]
DR RefSeq; XP_016858444.1; XM_017002955.1. [Q15047-2]
DR PDB; 3DLM; X-ray; 1.77 A; A=196-402.
DR PDB; 4X3S; X-ray; 1.60 A; C/D=1165-1174.
DR PDB; 5KCH; X-ray; 1.70 A; A=196-403.
DR PDB; 5KCO; X-ray; 1.47 A; A=196-403.
DR PDB; 5KE2; X-ray; 1.56 A; A=196-402.
DR PDB; 5KE3; X-ray; 1.70 A; A=196-402.
DR PDB; 5KH6; X-ray; 2.05 A; A=196-400.
DR PDB; 5QT1; X-ray; 1.58 A; A=196-397.
DR PDB; 5QT2; X-ray; 1.59 A; A=196-397.
DR PDB; 6AU2; X-ray; 1.63 A; A=196-402.
DR PDB; 6AU3; X-ray; 1.80 A; A=196-402.
DR PDB; 6BHD; X-ray; 1.25 A; A=190-410.
DR PDB; 6BHE; X-ray; 1.35 A; A=190-410.
DR PDB; 6BHG; X-ray; 1.45 A; A=190-410.
DR PDB; 6BHH; X-ray; 1.85 A; A=190-410.
DR PDB; 6BHI; X-ray; 1.40 A; A=190-410.
DR PDB; 6BPI; X-ray; 1.64 A; A=196-402.
DR PDB; 7C9N; X-ray; 2.47 A; A/B=190-410.
DR PDB; 7CAJ; X-ray; 2.20 A; A/D=190-410.
DR PDB; 7CD9; X-ray; 1.60 A; A/B=190-410.
DR PDB; 7CJT; X-ray; 2.47 A; A/B/C/D=190-410.
DR PDBsum; 3DLM; -.
DR PDBsum; 4X3S; -.
DR PDBsum; 5KCH; -.
DR PDBsum; 5KCO; -.
DR PDBsum; 5KE2; -.
DR PDBsum; 5KE3; -.
DR PDBsum; 5KH6; -.
DR PDBsum; 5QT1; -.
DR PDBsum; 5QT2; -.
DR PDBsum; 6AU2; -.
DR PDBsum; 6AU3; -.
DR PDBsum; 6BHD; -.
DR PDBsum; 6BHE; -.
DR PDBsum; 6BHG; -.
DR PDBsum; 6BHH; -.
DR PDBsum; 6BHI; -.
DR PDBsum; 6BPI; -.
DR PDBsum; 7C9N; -.
DR PDBsum; 7CAJ; -.
DR PDBsum; 7CD9; -.
DR PDBsum; 7CJT; -.
DR AlphaFoldDB; Q15047; -.
DR SMR; Q15047; -.
DR BioGRID; 115202; 165.
DR CORUM; Q15047; -.
DR DIP; DIP-31029N; -.
DR IntAct; Q15047; 260.
DR MINT; Q15047; -.
DR STRING; 9606.ENSP00000271640; -.
DR BindingDB; Q15047; -.
DR ChEMBL; CHEMBL2321646; -.
DR GlyGen; Q15047; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15047; -.
DR PhosphoSitePlus; Q15047; -.
DR BioMuta; SETDB1; -.
DR DMDM; 25091210; -.
DR EPD; Q15047; -.
DR jPOST; Q15047; -.
DR MassIVE; Q15047; -.
DR MaxQB; Q15047; -.
DR PaxDb; Q15047; -.
DR PeptideAtlas; Q15047; -.
DR PRIDE; Q15047; -.
DR ProteomicsDB; 60397; -. [Q15047-1]
DR ProteomicsDB; 60398; -. [Q15047-2]
DR ProteomicsDB; 60399; -. [Q15047-3]
DR Antibodypedia; 20300; 408 antibodies from 41 providers.
DR DNASU; 9869; -.
DR Ensembl; ENST00000271640.9; ENSP00000271640.5; ENSG00000143379.13. [Q15047-1]
DR Ensembl; ENST00000368962.6; ENSP00000357958.2; ENSG00000143379.13. [Q15047-2]
DR Ensembl; ENST00000368969.8; ENSP00000357965.4; ENSG00000143379.13. [Q15047-3]
DR GeneID; 9869; -.
DR KEGG; hsa:9869; -.
DR UCSC; uc001evu.3; human. [Q15047-1]
DR CTD; 9869; -.
DR DisGeNET; 9869; -.
DR GeneCards; SETDB1; -.
DR HGNC; HGNC:10761; SETDB1.
DR HPA; ENSG00000143379; Low tissue specificity.
DR MIM; 604396; gene.
DR neXtProt; NX_Q15047; -.
DR OpenTargets; ENSG00000143379; -.
DR PharmGKB; PA35679; -.
DR VEuPathDB; HostDB:ENSG00000143379; -.
DR eggNOG; KOG1141; Eukaryota.
DR GeneTree; ENSGT00940000157471; -.
DR HOGENOM; CLU_003279_1_0_1; -.
DR InParanoid; Q15047; -.
DR OMA; IRAVTNC; -.
DR OrthoDB; 183716at2759; -.
DR PhylomeDB; Q15047; -.
DR TreeFam; TF106411; -.
DR BioCyc; MetaCyc:HS07042-MON; -.
DR BRENDA; 2.1.1.355; 2681.
DR BRENDA; 2.1.1.366; 2681.
DR BRENDA; 2.1.1.368; 2681.
DR PathwayCommons; Q15047; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR SignaLink; Q15047; -.
DR SIGNOR; Q15047; -.
DR BioGRID-ORCS; 9869; 273 hits in 1124 CRISPR screens.
DR ChiTaRS; SETDB1; human.
DR EvolutionaryTrace; Q15047; -.
DR GeneWiki; SETDB1; -.
DR GenomeRNAi; 9869; -.
DR Pharos; Q15047; Tbio.
DR PRO; PR:Q15047; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q15047; protein.
DR Bgee; ENSG00000143379; Expressed in sural nerve and 183 other tissues.
DR ExpressionAtlas; Q15047; baseline and differential.
DR Genevisible; Q15047; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
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:0070828; P:heterochromatin organization; IBA:GO_Central.
DR GO; GO:0051567; P:histone H3-K9 methylation; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IMP:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP: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 3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
KW Coiled coil; Cytoplasm; Isopeptide bond; Metal-binding; Methylation;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation; Zinc.
FT CHAIN 1..1291
FT /note="Histone-lysine N-methyltransferase SETDB1"
FT /id="PRO_0000186064"
FT DOMAIN 257..320
FT /note="Tudor 1"
FT DOMAIN 347..403
FT /note="Tudor 2"
FT DOMAIN 594..665
FT /note="MBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT DOMAIN 727..800
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 803..1266
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 1275..1291
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 108..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..545
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 868..1160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 18..64
FT /evidence="ECO:0000255"
FT COMPBIAS 108..123
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 432..448
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..469
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..535
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 893..910
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 915..947
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 951..967
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 972..1007
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1034..1053
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1078..1140
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 729
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 729
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 731
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 735
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 735
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 741
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 743
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 781
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 781
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 785
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 787
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 792
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 813..815
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 851
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 853
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1220
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1223..1224
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1286
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:0000250|UniProtKB:O88974"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88974"
FT MOD_RES 120
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O88974"
FT MOD_RES 1025
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1066
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1170
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1170
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1178
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1178
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CROSSLNK 182
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 182
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT CROSSLNK 1032
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 1032
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1038
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1069
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1149
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 381..397
FT /note="DDKRCEWIYRGSTRLEP -> VLFFSTILEAEVGGGGT (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_002217"
FT VAR_SEQ 398..1291
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_002218"
FT VAR_SEQ 1254
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034600"
FT VARIANT 236
FT /note="N -> S (in dbSNP:rs2271075)"
FT /id="VAR_014284"
FT VARIANT 506
FT /note="P -> S (in dbSNP:rs17852587)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031281"
FT VARIANT 824
FT /note="A -> G (in dbSNP:rs2691551)"
FT /id="VAR_014286"
FT VARIANT 824
FT /note="A -> P (in dbSNP:rs2814054)"
FT /id="VAR_014285"
FT MUTAGEN 729..731
FT /note="CDC->LDP: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11959841"
FT MUTAGEN 1224
FT /note="H->K: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11959841"
FT MUTAGEN 1226
FT /note="C->A: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11959841"
FT MUTAGEN 1279
FT /note="C->Y: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11959841"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 213..224
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 227..237
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:6BHD"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:6BHD"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:6BHE"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 274..283
FT /evidence="ECO:0007829|PDB:6BHD"
FT TURN 287..290
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:6BHD"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 310..315
FT /evidence="ECO:0007829|PDB:6BHD"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:6BHD"
FT HELIX 327..339
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 353..358
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 361..371
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 374..379
FT /evidence="ECO:0007829|PDB:6BHD"
FT TURN 380..383
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:6BHD"
FT HELIX 396..403
FT /evidence="ECO:0007829|PDB:6BHD"
FT STRAND 1167..1172
FT /evidence="ECO:0007829|PDB:4X3S"
SQ 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
