SETB2_MOUSE
ID SETB2_MOUSE Reviewed; 713 AA.
AC Q8C267;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Histone-lysine N-methyltransferase SETDB2;
DE EC=2.1.1.366 {ECO:0000250|UniProtKB:Q96T68};
DE AltName: Full=SET domain bifurcated 2;
GN Name=Setdb2; Synonyms=Gm293;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=NOD;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Histone methyltransferase involved in left-right axis
CC specification in early development and mitosis. Specifically
CC trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 is a specific
CC tag for epigenetic transcriptional repression that recruits HP1 (CBX1,
CC CBX3 and/or CBX5) proteins to methylated histones. Contributes to
CC H3K9me3 in both the interspersed repetitive elements and centromere-
CC associated repeats. Plays a role in chromosome condensation and
CC segregation during mitosis (By similarity). {ECO:0000250}.
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;
CC Evidence={ECO:0000250|UniProtKB:Q96T68};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C267-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C267-2; Sequence=VSP_024063, VSP_024064, VSP_024065;
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 -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; AK089197; BAC40789.1; -; mRNA.
DR EMBL; AC114007; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; Q8C267; -.
DR IntAct; Q8C267; 1.
DR MINT; Q8C267; -.
DR STRING; 10090.ENSMUSP00000093450; -.
DR iPTMnet; Q8C267; -.
DR PhosphoSitePlus; Q8C267; -.
DR jPOST; Q8C267; -.
DR MaxQB; Q8C267; -.
DR PaxDb; Q8C267; -.
DR PRIDE; Q8C267; -.
DR ProteomicsDB; 261324; -. [Q8C267-1]
DR ProteomicsDB; 261325; -. [Q8C267-2]
DR Antibodypedia; 23922; 240 antibodies from 36 providers.
DR Ensembl; ENSMUST00000095775; ENSMUSP00000093450; ENSMUSG00000071350. [Q8C267-1]
DR Ensembl; ENSMUST00000111253; ENSMUSP00000106884; ENSMUSG00000071350. [Q8C267-2]
DR UCSC; uc007uei.1; mouse. [Q8C267-1]
DR UCSC; uc007uej.1; mouse. [Q8C267-2]
DR MGI; MGI:2685139; Setdb2.
DR VEuPathDB; HostDB:ENSMUSG00000071350; -.
DR eggNOG; KOG1141; Eukaryota.
DR GeneTree; ENSGT00940000158209; -.
DR HOGENOM; CLU_1834517_0_0_1; -.
DR InParanoid; Q8C267; -.
DR PhylomeDB; Q8C267; -.
DR TreeFam; TF106411; -.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR PRO; PR:Q8C267; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8C267; protein.
DR Bgee; ENSMUSG00000071350; Expressed in spermatogonium and 198 other tissues.
DR ExpressionAtlas; Q8C267; baseline and differential.
DR Genevisible; Q8C267; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0070828; P:heterochromatin organization; IBA:GO_Central.
DR GO; GO:0051567; P:histone H3-K9 methylation; ISS:UniProtKB.
DR GO; GO:0070986; P:left/right axis specification; ISS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IBA:GO_Central.
DR Gene3D; 2.170.270.10; -; 2.
DR InterPro; IPR016177; DNA-bd_dom_sf.
DR InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR InterPro; IPR007728; Pre-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF01429; MBD; 1.
DR Pfam; PF05033; Pre-SET; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00391; MBD; 1.
DR SMART; SM00468; PreSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF54171; SSF54171; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50982; MBD; 1.
DR PROSITE; PS50867; PRE_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell cycle; Cell division; Chromatin regulator;
KW Chromosome; Developmental protein; Metal-binding; Methyltransferase;
KW Mitosis; Nucleus; Reference proteome; S-adenosyl-L-methionine; Transferase;
KW Zinc.
FT CHAIN 1..713
FT /note="Histone-lysine N-methyltransferase SETDB2"
FT /id="PRO_0000281824"
FT DOMAIN 161..233
FT /note="MBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT DOMAIN 294..367
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 370..688
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 78..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..608
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..538
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 593..607
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 308
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 348
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 348
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 354
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 380..382
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 642
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 645..646
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 648
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 701
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 703
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 708
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT VAR_SEQ 70..86
FT /note="GMFITYSNPEVNTHRSN -> D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_024063"
FT VAR_SEQ 119..156
FT /note="SPGKKVFLPVKNKADNLVKKEAPLHISFHRHICSRTCL -> YVYVIRVSAP
FT SVCCLLNIPKSLTPFIKFNSRCLCLLVN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_024064"
FT VAR_SEQ 157..713
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_024065"
SQ SEQUENCE 713 AA; 80636 MW; C4E750F01ED4231A CRC64;
MEEKNGDAKT FWMELQDDGK VDLMFEKTQN VLHSLKQKIK DGSATNGDYV QAMNLVNEAT
LSNTQTLEKG MFITYSNPEV NTHRSNHTPV TQSEQENKSS AVPSASCDNS CPKGCTIPSP
GKKVFLPVKN KADNLVKKEA PLHISFHRHI CSRTCLMETP LSLKGENPLQ LPIRCHFQRR
HAKTNSHSSA LHVNYKTPCG RNLRNMEEVF HYLLETECNF LFTDNFSFNT YVQLTRNHPK
QNEVVSDVDI SNGVESVSIP FCNEIDNSKL PRFKYRNTVW PRIYHLNFSN MFSDSCDCSE
GCIDIKKCAC LQLTAKNAKA CPLSSDGECA GYKYKRLQRL IPTGIYECNL LCKCNKQMCQ
NRVIQHGVRV RLQVFKSEKK GWGVRCLDDI DKGTFVCIYS GRLLRRATPE KTNIGENGRE
QQHIVKNSFS KKRKLEVVCS DCDAHCDSPK AEDCPPKLSG DLKEPAVEMN HRNISRTQHH
SVIRRTKSKT TVFHYSEKNM GFVCSDSAAP EDKNGFKPAQ EHVNSEARRA HEDLSSNPAG
DSEDTQLTES DVIDITASRE DSAPAYRCKH ATIVDRKDTK QVLEVPGKKS QEEEPAASQS
QQALCDEELP SERTKIPSAS LMQLSKESLF LLDASKEGNV GRFLNHSCCP NLWVQNVFVE
THDRNFPLVA FFTNRYVKAR TELTWDYGYE AGATPAKEIL CQCGFNKCRK KLI
