SUZ12_MOUSE
ID SUZ12_MOUSE Reviewed; 741 AA.
AC Q80U70; B1AQE5; Q80Y10; Q99L07;
DT 11-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Polycomb protein Suz12;
DE AltName: Full=Suppressor of zeste 12 protein homolog;
GN Name=Suz12; Synonyms=D11Ertd530e, Kiaa0160;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
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).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Brain, and Kidney;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15385962; DOI=10.1038/sj.emboj.7600402;
RA Pasini D., Bracken A.P., Jensen M.R., Lazzerini Denchi E., Helin K.;
RT "Suz12 is essential for mouse development and for EZH2 histone
RT methyltransferase activity.";
RL EMBO J. 23:4061-4071(2004).
RN [5]
RP FUNCTION.
RX PubMed=15516932; DOI=10.1038/ng1467;
RA Umlauf D., Goto Y., Cao R., Cerqueira F., Wagschal A., Zhang Y., Feil R.;
RT "Imprinting along the Kcnq1 domain on mouse chromosome 7 involves
RT repressive histone methylation and recruitment of Polycomb group
RT complexes.";
RL Nat. Genet. 36:1296-1300(2004).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=15684044; DOI=10.1073/pnas.0409875102;
RA Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M.,
RA Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J.,
RA Reinberg D.;
RT "Composition and histone substrates of polycomb repressive group complexes
RT change during cellular differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005).
RN [7]
RP INTERACTION WITH WDR77.
RX PubMed=16712789; DOI=10.1016/j.bbrc.2006.05.014;
RA Furuno K., Masatsugu T., Sonoda M., Sasazuki T., Yamamoto K.;
RT "Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that
RT binds to histone H2A selectively in vitro.";
RL Biochem. Biophys. Res. Commun. 345:1051-1058(2006).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=16415857; DOI=10.1038/ncb1351;
RA Kalantry S., Mills K.C., Yee D., Otte A.P., Panning B., Magnuson T.;
RT "The Polycomb group protein Eed protects the inactive X-chromosome from
RT differentiation-induced reactivation.";
RL Nat. Cell Biol. 8:195-202(2006).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17339329; DOI=10.1128/mcb.01432-06;
RA Pasini D., Bracken A.P., Hansen J.B., Capillo M., Helin K.;
RT "The polycomb group protein Suz12 is required for embryonic stem cell
RT differentiation.";
RL Mol. Cell. Biol. 27:3769-3779(2007).
RN [10]
RP IDENTIFICATION IN THE PRC2/EZH1 COMPLEX.
RX PubMed=19026780; DOI=10.1016/j.molcel.2008.10.016;
RA Shen X., Liu Y., Hsu Y.-J., Fujiwara Y., Kim J., Mao X., Yuan G.-C.,
RA Orkin S.H.;
RT "EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in
RT maintaining stem cell identity and executing pluripotency.";
RL Mol. Cell 32:491-502(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548 AND SER-585, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, 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 [13]
RP IDENTIFICATION IN THE PRC2 COMPLEX.
RX PubMed=20144788; DOI=10.1016/j.stem.2009.12.014;
RA Walker E., Chang W.Y., Hunkapiller J., Cagney G., Garcha K., Torchia J.,
RA Krogan N.J., Reiter J.F., Stanford W.L.;
RT "Polycomb-like 2 associates with PRC2 and regulates transcriptional
RT networks during mouse embryonic stem cell self-renewal and
RT differentiation.";
RL Cell Stem Cell 6:153-166(2010).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=22226355; DOI=10.1016/j.stem.2011.12.006;
RA Morey L., Pascual G., Cozzuto L., Roma G., Wutz A., Benitah S.A.,
RA Di Croce L.;
RT "Nonoverlapping functions of the Polycomb group Cbx family of proteins in
RT embryonic stem cells.";
RL Cell Stem Cell 10:47-62(2012).
RN [15]
RP INTERACTION WITH ARNTL/BMAL1.
RX PubMed=23970558; DOI=10.1126/science.1240636;
RA Nguyen K.D., Fentress S.J., Qiu Y., Yun K., Cox J.S., Chawla A.;
RT "Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi)
RT inflammatory monocytes.";
RL Science 341:1483-1488(2013).
CC -!- FUNCTION: Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2
CC complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of
CC histone H3, leading to transcriptional repression of the affected
CC target gene. The PRC2/EED-EZH2 complex may also serve as a recruiting
CC platform for DNA methyltransferases, thereby linking two epigenetic
CC repression systems (By similarity). Genes repressed by the PRC2/EED-
CC EZH2 complex include HOXA7, HOXB6 and HOXC8.
CC {ECO:0000250|UniProtKB:Q15022, ECO:0000269|PubMed:15385962,
CC ECO:0000269|PubMed:15516932, ECO:0000269|PubMed:17339329}.
CC -!- SUBUNIT: Component of the PRC2 complex, which consists of the core
CC subunits EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations
CC of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP
CC (PubMed:19026780, PubMed:20144788). Within the complex, interacts (via
CC C2H2 zinc finger domain) with JARID2 and EPOP; JARID2 and EPOP compete
CC for SUZ12 binding (By similarity). Also interacts with AEBP2 and PHF19
CC (By similarity). Forms a monomeric PRC2.2 (class 2) complex consisting
CC of at least SUZ12, RBBP4, AEBP2 and JARID2 (By similarity). Forms a
CC dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12,
CC RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric
CC structure which enhances PRC2 interaction with chromatin (By
CC similarity). The minimum components required for methyltransferase
CC activity of the PRC2/EZH2 complex are EED, EZH2 and SUZ12 (By
CC similarity). The PRC2 complex may also interact with DNMT1, DNMT3A,
CC DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12
CC subunit. Interacts with WDR77 (PubMed:16712789). Interacts with histone
CC H1. Interacts with CDYL (By similarity). Interacts with ARNTL/BMAL1
CC (PubMed:23970558). Interacts with EZHIP (via C-terminal region) (By
CC similarity). Interacts with ARMC12 (By similarity).
CC {ECO:0000250|UniProtKB:Q15022, ECO:0000269|PubMed:16712789,
CC ECO:0000269|PubMed:19026780, ECO:0000269|PubMed:20144788,
CC ECO:0000269|PubMed:23970558}.
CC -!- INTERACTION:
CC Q80U70; Q7TNS8: Epop; NbExp=2; IntAct=EBI-2526494, EBI-16024836;
CC Q80U70; Q61188: Ezh2; NbExp=10; IntAct=EBI-2526494, EBI-904311;
CC Q80U70; Q6AXH7: Ezh2; NbExp=3; IntAct=EBI-2526494, EBI-6876582;
CC Q80U70; Q62315: Jarid2; NbExp=13; IntAct=EBI-2526494, EBI-493592;
CC Q80U70; Q3UXZ9: Kdm5a; NbExp=2; IntAct=EBI-2526494, EBI-2531441;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16415857}. Chromosome
CC {ECO:0000269|PubMed:16415857}. Note=Localizes to the inactive X
CC chromosome in trophoblast stem cells.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic stem cells.
CC {ECO:0000269|PubMed:22226355}.
CC -!- DEVELOPMENTAL STAGE: Expression increases in prostate during prostate
CC tumor development. {ECO:0000269|PubMed:15684044}.
CC -!- PTM: Sumoylated, probably by PIAS2. {ECO:0000250|UniProtKB:Q15022}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit early embryonic lethality and
CC defects in gastrulation accompanied by reduced methylation of 'Lys-27'
CC of histone H3. {ECO:0000269|PubMed:15385962,
CC ECO:0000269|PubMed:17339329}.
CC -!- SIMILARITY: Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65495.1; Type=Miscellaneous discrepancy; Note=Unknown reasons.; Evidence={ECO:0000305};
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DR EMBL; AK122213; BAC65495.1; ALT_SEQ; Transcribed_RNA.
DR EMBL; AL591113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003922; AAH03922.1; -; mRNA.
DR EMBL; BC051099; AAH51099.1; -; mRNA.
DR EMBL; BC064461; AAH64461.1; -; mRNA.
DR CCDS; CCDS25125.1; -.
DR RefSeq; NP_001156490.1; NM_001163018.1.
DR RefSeq; NP_954666.1; NM_199196.2.
DR AlphaFoldDB; Q80U70; -.
DR SMR; Q80U70; -.
DR BioGRID; 206694; 29.
DR CORUM; Q80U70; -.
DR DIP; DIP-56045N; -.
DR IntAct; Q80U70; 19.
DR MINT; Q80U70; -.
DR STRING; 10090.ENSMUSP00000017692; -.
DR iPTMnet; Q80U70; -.
DR PhosphoSitePlus; Q80U70; -.
DR EPD; Q80U70; -.
DR jPOST; Q80U70; -.
DR MaxQB; Q80U70; -.
DR PaxDb; Q80U70; -.
DR PeptideAtlas; Q80U70; -.
DR PRIDE; Q80U70; -.
DR ProteomicsDB; 254611; -.
DR Antibodypedia; 27067; 379 antibodies from 38 providers.
DR DNASU; 52615; -.
DR Ensembl; ENSMUST00000017692; ENSMUSP00000017692; ENSMUSG00000017548.
DR GeneID; 52615; -.
DR KEGG; mmu:52615; -.
DR UCSC; uc007klc.1; mouse.
DR CTD; 23512; -.
DR MGI; MGI:1261758; Suz12.
DR VEuPathDB; HostDB:ENSMUSG00000017548; -.
DR eggNOG; KOG2350; Eukaryota.
DR GeneTree; ENSGT00390000012364; -.
DR InParanoid; Q80U70; -.
DR OMA; RNEKMFG; -.
DR OrthoDB; 516359at2759; -.
DR PhylomeDB; Q80U70; -.
DR TreeFam; TF323249; -.
DR Reactome; R-MMU-212300; PRC2 methylates histones and DNA.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR Reactome; R-MMU-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-8953750; Transcriptional Regulation by E2F6.
DR BioGRID-ORCS; 52615; 15 hits in 81 CRISPR screens.
DR ChiTaRS; Suz12; mouse.
DR PRO; PR:Q80U70; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q80U70; protein.
DR Bgee; ENSMUSG00000017548; Expressed in metanephric loop of Henle and 277 other tissues.
DR ExpressionAtlas; Q80U70; baseline and differential.
DR Genevisible; Q80U70; MM.
DR GO; GO:0005677; C:chromatin silencing complex; IDA:MGI.
DR GO; GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032993; C:protein-DNA complex; IDA:MGI.
DR GO; GO:1990904; C:ribonucleoprotein complex; IPI:MGI.
DR GO; GO:0001739; C:sex chromatin; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0008047; F:enzyme activator activity; ISS:UniProtKB.
DR GO; GO:0042054; F:histone methyltransferase activity; ISO:MGI.
DR GO; GO:0106222; F:lncRNA binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IPI:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IMP:MGI.
DR GO; GO:0016571; P:histone methylation; IMP:MGI.
DR GO; GO:0016574; P:histone ubiquitination; IMP:MGI.
DR GO; GO:0045596; P:negative regulation of cell differentiation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR InterPro; IPR019135; Polycomb_protein_VEFS-Box.
DR Pfam; PF09733; VEFS-Box; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Chromosome; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..741
FT /note="Polycomb protein Suz12"
FT /id="PRO_0000047058"
FT ZN_FING 450..473
FT /note="C2H2-type"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..108
FT /note="Interaction with JARID2 and EPOP"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
FT REGION 148..365
FT /note="Interaction with AEBP2 and PHF19"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
FT REGION 565..641
FT /note="VEFS-box"
FT REGION 689..741
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..719
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 585
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 74
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 75
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 77
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 77
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
FT CROSSLNK 225
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
FT CROSSLNK 392
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q15022"
SQ SEQUENCE 741 AA; 83026 MW; 4A6B6E52D24FAEF2 CRC64;
MAPQKHGGGG GGGSGPSAGS GGGGFGGSAA AVAAAASGGK SGGGGCGGGG SYSASSSSAA
AAAAAAGAAV LPVKKPKMEH VQADHELFLQ AFEKPTQIYR FLRTRNLIAP IFLHRTLTYM
SHRNSRTSIK RKTFKVDDML SKVEKMKGEQ ESHSLSAHLQ LTFTGFFHKN DKPSQNSENE
QNSVTLEVLL VKVCHKKRKD VSCPIRQVPT GKKQVPLNPD LNQTKPGNFP SLAVSSNEFE
PSNSHMVKSY SLLFRVTRPG RREFNGMING ETNENIDVSE ELPARRKRNR EDGEKTFVAQ
MTVFDKNRRL QLLDGEYEVA MQEMEECPIS KKRATWETIL DGKRLPPFET FSQGPTLQFT
LRWTGETNDK STAPVAKPLA TRNSESLHQE NKPGSVKPAQ TIAVKETLTT ELQTRKEKDN
SNESRQKLRI FYQFLYNNNT RQQTEARDDL HCPWCTLNCR KLYSLLKHLK LCHSRFIFNY
VYHPKGARID VSINECYDGS YAGNPQDIHR QPGFAFSRNG PVKRTPITHI LVCRPKRTKA
SMSEFLESED GEVEQQRTYS SGHNRLYFHS DTCLPLRPQE MEVDSEDEKD PEWLREKTIT
QIEEFSDVNE GEKEVMKLWN LHVMKHGFIA DNQMNHACML FVENYGQKII KKNLCRNFML
HLVSMHDFNL ISIMSIDKAV TKLREMQQKL EKGESATPSN EEIAEEQNGT ANGFSETNSK
EKALETDGVS GVPKQSKKQK L
