CBX4_HUMAN
ID CBX4_HUMAN Reviewed; 560 AA.
AC O00257; B1PJR7; Q6TPI8; Q96C04;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=E3 SUMO-protein ligase CBX4;
DE EC=2.3.2.-;
DE AltName: Full=Chromobox protein homolog 4;
DE AltName: Full=Polycomb 2 homolog;
DE Short=Pc2;
DE Short=hPc2;
GN Name=CBX4;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=9315667; DOI=10.1128/mcb.17.10.6076;
RA Satijn D.P.E., Olson D.J., van der Vlag J., Hamer K.M., Lambrechts C.,
RA Masselink H., Gunster M.J., Sewalt R.G.A.B., van Driel R., Otte A.P.;
RT "Interference with the expression of a novel human polycomb protein, hPc2,
RT results in cellular transformation and apoptosis.";
RL Mol. Cell. Biol. 17:6076-6086(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=19266028; DOI=10.1371/journal.pgen.1000397;
RA Salichs E., Ledda A., Mularoni L., Alba M.M., de la Luna S.;
RT "Genome-wide analysis of histidine repeats reveals their role in the
RT localization of human proteins to the nuclear speckles compartment.";
RL PLoS Genet. 5:E1000397-E1000397(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Liu M., Cheng J., Wang L.;
RT "Cloning and identification of NS5ATP1-binding protein 16.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 457-560 (ISOFORM 1).
RX PubMed=9199346; DOI=10.1128/mcb.17.7.4105;
RA Satijn D.P.E., Gunster M.J., van der Vlag J., Hamer K.M., Schul W.,
RA Alkema M.J., Saurin A.J., Freemont P.S., van Driel R., Otte A.P.;
RT "RING1 is associated with the polycomb group protein complex and acts as a
RT transcriptional repressor.";
RL Mol. Cell. Biol. 17:4105-4113(1997).
RN [7]
RP INTERACTION WITH SUV39H1.
RX PubMed=12101246; DOI=10.1128/mcb.22.15.5539-5553.2002;
RA Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L.,
RA Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P.;
RT "Selective interactions between vertebrate polycomb homologs and the
RT SUV39H1 histone lysine methyltransferase suggest that histone H3-K9
RT methylation contributes to chromosomal targeting of Polycomb group
RT proteins.";
RL Mol. Cell. Biol. 22:5539-5553(2002).
RN [8]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A
RP PRC1-LIKE HPRC-H COMPLEX WITH BMI1; CBX2; CBX8; PHC1; PHC2; PHC3; RING1 AND
RP RNF2.
RX PubMed=12167701; DOI=10.1128/mcb.22.17.6070-6078.2002;
RA Levine S.S., Weiss A., Erdjument-Bromage H., Shao Z., Tempst P.,
RA Kingston R.E.;
RT "The core of the polycomb repressive complex is compositionally and
RT functionally conserved in flies and humans.";
RL Mol. Cell. Biol. 22:6070-6078(2002).
RN [9]
RP FUNCTION, SUMOYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12679040; DOI=10.1016/s0092-8674(03)00159-4;
RA Kagey M.H., Melhuish T.A., Wotton D.;
RT "The polycomb protein Pc2 is a SUMO E3.";
RL Cell 113:127-137(2003).
RN [10]
RP SUMOYLATION AT LYS-494.
RX PubMed=15592428; DOI=10.1038/sj.emboj.7600506;
RA Kagey M.H., Melhuish T.A., Powers S.E., Wotton D.;
RT "Multiple activities contribute to Pc2 E3 function.";
RL EMBO J. 24:108-119(2005).
RN [11]
RP FUNCTION.
RX PubMed=16061479; DOI=10.1074/jbc.m504477200;
RA Long J., Zuo D., Park M.;
RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates
RT transcriptional repression of E-cadherin.";
RL J. Biol. Chem. 280:35477-35489(2005).
RN [12]
RP FUNCTION, INTERACTION WITH HIPK2, SUMOYLATION, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT THR-497.
RX PubMed=17018294; DOI=10.1016/j.molcel.2006.08.004;
RA Roscic A., Moeller A., Calzado M.A., Renner F., Wimmer V.C., Gresko E.,
RA Luedi K.S., Schmitz M.L.;
RT "Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its
RT substrate protein HIPK2.";
RL Mol. Cell 24:77-89(2006).
RN [13]
RP IDENTIFICATION BY 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 [14]
RP INTERACTION WITH H3C15; H3C1 AND RNF2, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ILE-16.
RX PubMed=18927235; DOI=10.1073/pnas.0805317105;
RA Vincenz C., Kerppola T.K.;
RT "Different polycomb group CBX family proteins associate with distinct
RT regions of chromatin using nonhomologous protein sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16572-16577(2008).
RN [15]
RP FUNCTION, AND IDENTIFICATION IN A PRC1-LIKE COMPLEX.
RX PubMed=19636380; DOI=10.1371/journal.pone.0006380;
RA Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K., Nicholls J.,
RA Rodriguez-Niedenfuhr M., Gil J., Peters G.;
RT "Several distinct polycomb complexes regulate and co-localize on the INK4a
RT tumor suppressor locus.";
RL PLoS ONE 4:E6380-E6380(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-149, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY (ISOFORM 2), IDENTIFICATION
RP IN A PRC1-LIKE COMPLEX, SELF-ASSOCIATION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF SER-434.
RX PubMed=21282530; DOI=10.1074/mcp.m110.002642;
RA Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O.;
RT "Interaction proteomics analysis of polycomb proteins defines distinct PRC1
RT Complexes in mammalian cells.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [18]
RP FUNCTION IN ZNF131 SUMOYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-494 AND THR-497.
RX PubMed=22467880; DOI=10.1074/jbc.m111.336354;
RA Oh Y., Chung K.C.;
RT "Small ubiquitin-like modifier (SUMO) modification of zinc finger protein
RT 131 potentiates its negative effect on estrogen signaling.";
RL J. Biol. Chem. 287:17517-17529(2012).
RN [19]
RP FUNCTION.
RX PubMed=22825850; DOI=10.1074/jbc.m112.390120;
RA Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.;
RT "DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation
RT regulates p53 transcriptional activation.";
RL J. Biol. Chem. 287:30789-30799(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-467, AND IDENTIFICATION BY
RP 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 [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-106; LYS-114; LYS-149; LYS-205;
RP LYS-212 AND LYS-280, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-149; LYS-212 AND LYS-280, 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 [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-280, AND IDENTIFICATION BY MASS
RP 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 [25]
RP INTERACTION WITH SUMO1P1/SUMO5.
RX PubMed=27211601; DOI=10.1038/srep26509;
RA Liang Y.C., Lee C.C., Yao Y.L., Lai C.C., Schmitz M.L., Yang W.M.;
RT "SUMO5, a novel poly-sumo isoform, regulates pml nuclear bodies.";
RL Sci. Rep. 6:26509-26509(2016).
RN [26]
RP INTERACTION WITH PRDM1.
RX PubMed=28842558; DOI=10.1038/s41467-017-00476-w;
RA Wang W.F., Yan L., Liu Z., Liu L.X., Lin J., Liu Z.Y., Chen X.P., Zhang W.,
RA Xu Z.Z., Shi T., Li J.M., Zhao Y.L., Meng G., Xia Y., Li J.Y., Zhu J.;
RT "HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal
RT misfolded Blimp-1s in lymphoma cells.";
RL Nat. Commun. 8:363-363(2017).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-77; LYS-106; LYS-114; LYS-125;
RP LYS-149; LYS-157; LYS-167; LYS-178; LYS-191; LYS-205; LYS-212; LYS-223;
RP LYS-249; LYS-268; LYS-278; LYS-280; LYS-320; LYS-352; LYS-365 AND LYS-494,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [28]
RP STRUCTURE BY NMR OF 8-65.
RG Structural genomics consortium (SGC);
RT "Solution NMR structure of the chromo domain of the chromobox protein
RT homolog 4.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF 8-62.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human chromobox homolog 4 (cbx4).";
RL Submitted (SEP-2009) to the PDB data bank.
CC -!- FUNCTION: E3 SUMO-protein ligase which facilitates SUMO1 conjugation by
CC UBE2I (PubMed:12679040). Involved in the sumoylation of HNRNPK, a
CC p53/TP53 transcriptional coactivator, hence indirectly regulates
CC p53/TP53 transcriptional activation resulting in p21/CDKN1A expression.
CC Monosumoylates ZNF131 (PubMed:22825850). {ECO:0000269|PubMed:12679040,
CC ECO:0000269|PubMed:22825850}.
CC -!- FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1-like
CC complex, a complex class required to maintain the transcriptionally
CC repressive state of many genes, including Hox genes, throughout
CC development (PubMed:12167701, PubMed:19636380, PubMed:21282530). PcG
CC PRC1 complex acts via chromatin remodeling and modification of
CC histones; it mediates monoubiquitination of histone H2A 'Lys-119',
CC rendering chromatin heritably changed in its expressibility
CC (PubMed:12167701, PubMed:19636380, PubMed:21282530). Binds to histone
CC H3 trimethylated at 'Lys-9' (H3K9me3) (By similarity). Plays a role in
CC the lineage differentiation of the germ layers in embryonic development
CC (By similarity). {ECO:0000250|UniProtKB:O55187,
CC ECO:0000269|PubMed:12167701, ECO:0000269|PubMed:19636380,
CC ECO:0000269|PubMed:21282530}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Interacts with histone H3-K9Me3 (By similarity). Interacts
CC with CHTOP (By similarity). Component of a PRC1-like complex
CC (PubMed:12167701, PubMed:19636380, PubMed:21282530). The composition of
CC the PRC1 complex differs between the PRC1 complex in pluripotent
CC embryonic stem cells containing RNF2, CBX7 and PCGF2, and the PRC1
CC complex in differentiating cells containing RNF2, CBX2, CBX4 and BMI1
CC (By similarity). Self-associates (PubMed:21282530). Interacts with
CC SUV39H1 and HIPK2 (PubMed:12101246, PubMed:17018294). Interacts with
CC CSNK2B (PubMed:21282530). May interact with H3C15, H3C1 and RNF2
CC (PubMed:18927235). Interacts with SUMO1P1/SUMO5 (PubMed:27211601).
CC Interacts with PRDM1/Blimp-1 (PubMed:28842558).
CC {ECO:0000250|UniProtKB:O55187, ECO:0000269|PubMed:12101246,
CC ECO:0000269|PubMed:12167701, ECO:0000269|PubMed:17018294,
CC ECO:0000269|PubMed:18927235, ECO:0000269|PubMed:19636380,
CC ECO:0000269|PubMed:21282530, ECO:0000269|PubMed:27211601,
CC ECO:0000269|PubMed:28842558}.
CC -!- INTERACTION:
CC O00257; P35226: BMI1; NbExp=8; IntAct=EBI-722425, EBI-2341576;
CC O00257; Q9HC52: CBX8; NbExp=4; IntAct=EBI-722425, EBI-712912;
CC O00257; Q13363: CTBP1; NbExp=4; IntAct=EBI-722425, EBI-908846;
CC O00257; Q16665: HIF1A; NbExp=15; IntAct=EBI-722425, EBI-447269;
CC O00257; Q99496: RNF2; NbExp=5; IntAct=EBI-722425, EBI-722416;
CC O00257; P63165: SUMO1; NbExp=3; IntAct=EBI-722425, EBI-80140;
CC O00257; P31946: YWHAB; NbExp=2; IntAct=EBI-722425, EBI-359815;
CC O00257-3; A6NKF2: ARID3C; NbExp=3; IntAct=EBI-4392727, EBI-12805486;
CC O00257-3; P35226: BMI1; NbExp=2; IntAct=EBI-4392727, EBI-2341576;
CC O00257-3; P55212: CASP6; NbExp=3; IntAct=EBI-4392727, EBI-718729;
CC O00257-3; P06307: CCK; NbExp=3; IntAct=EBI-4392727, EBI-6624398;
CC O00257-3; P28329-3: CHAT; NbExp=3; IntAct=EBI-4392727, EBI-25837549;
CC O00257-3; P68400: CSNK2A1; NbExp=2; IntAct=EBI-4392727, EBI-347804;
CC O00257-3; P67870: CSNK2B; NbExp=2; IntAct=EBI-4392727, EBI-348169;
CC O00257-3; P22607: FGFR3; NbExp=3; IntAct=EBI-4392727, EBI-348399;
CC O00257-3; P06396: GSN; NbExp=3; IntAct=EBI-4392727, EBI-351506;
CC O00257-3; O00291: HIP1; NbExp=3; IntAct=EBI-4392727, EBI-473886;
CC O00257-3; P30519: HMOX2; NbExp=3; IntAct=EBI-4392727, EBI-712096;
CC O00257-3; P13473-2: LAMP2; NbExp=3; IntAct=EBI-4392727, EBI-21591415;
CC O00257-3; Q9BYE7: PCGF6; NbExp=2; IntAct=EBI-4392727, EBI-1048026;
CC O00257-3; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-4392727, EBI-5280197;
CC O00257-3; P62826: RAN; NbExp=3; IntAct=EBI-4392727, EBI-286642;
CC O00257-3; Q99496: RNF2; NbExp=2; IntAct=EBI-4392727, EBI-722416;
CC O00257-3; P19474: TRIM21; NbExp=3; IntAct=EBI-4392727, EBI-81290;
CC O00257-3; P62258: YWHAE; NbExp=2; IntAct=EBI-4392727, EBI-356498;
CC O00257-3; P63104: YWHAZ; NbExp=2; IntAct=EBI-4392727, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12679040,
CC ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:18927235,
CC ECO:0000269|PubMed:21282530}. Nucleus speckle
CC {ECO:0000269|PubMed:19266028}. Note=Localization to nuclear polycomb
CC bodies is required for ZNF131 sumoylation (PubMed:22467880). Localized
CC in distinct foci on chromatin (PubMed:18927235).
CC {ECO:0000269|PubMed:18927235, ECO:0000269|PubMed:22467880}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00257-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00257-3; Sequence=VSP_041599;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The polyhistidine repeat may act as a targeting signal to
CC nuclear speckles. {ECO:0000269|PubMed:19266028}.
CC -!- PTM: Phosphorylated on Thr-497 by HIPK2 upon DNA damage. This
CC phosphorylation stimulates E3 SUMO-protein ligase activity and promotes
CC sumoylation on Lys-494, as well as sumoylation of other target
CC proteins, such as HNRNPK. {ECO:0000269|PubMed:12679040,
CC ECO:0000269|PubMed:15592428, ECO:0000269|PubMed:17018294}.
CC -!- MISCELLANEOUS: The human orthologs of the Drosophila Polycomb group
CC protein Pc are CBX2, CBX4, CBX6, CBX7 and CBX8. These show distinct
CC nuclear localizations, contribute differently to transcriptional
CC repression, and appear to be part of distinct PRC1-like protein
CC complexes. The hPRC-H complex purified in PubMed:12167701 probably
CC presents a mixture of different complexes containing different Polycomb
CC group proteins.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14967.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF013956; AAB80718.1; -; mRNA.
DR EMBL; EU439707; ACA49234.1; -; mRNA.
DR EMBL; AY390430; AAQ97596.1; -; mRNA.
DR EMBL; AC100791; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014967; AAH14967.1; ALT_SEQ; mRNA.
DR EMBL; U94344; AAB62734.1; -; mRNA.
DR CCDS; CCDS32758.1; -. [O00257-1]
DR RefSeq; NP_003646.2; NM_003655.2. [O00257-1]
DR PDB; 2K28; NMR; -; A=8-65.
DR PDB; 3I8Z; X-ray; 1.51 A; A=8-62.
DR PDB; 5EPL; X-ray; 1.81 A; A/B=8-65.
DR PDBsum; 2K28; -.
DR PDBsum; 3I8Z; -.
DR PDBsum; 5EPL; -.
DR AlphaFoldDB; O00257; -.
DR BMRB; O00257; -.
DR SMR; O00257; -.
DR BioGRID; 114105; 205.
DR CORUM; O00257; -.
DR DIP; DIP-42042N; -.
DR ELM; O00257; -.
DR IntAct; O00257; 114.
DR MINT; O00257; -.
DR STRING; 9606.ENSP00000269397; -.
DR BindingDB; O00257; -.
DR ChEMBL; CHEMBL3232685; -.
DR iPTMnet; O00257; -.
DR PhosphoSitePlus; O00257; -.
DR BioMuta; CBX4; -.
DR EPD; O00257; -.
DR jPOST; O00257; -.
DR MassIVE; O00257; -.
DR MaxQB; O00257; -.
DR PaxDb; O00257; -.
DR PeptideAtlas; O00257; -.
DR PRIDE; O00257; -.
DR ProteomicsDB; 47811; -. [O00257-1]
DR ProteomicsDB; 47812; -. [O00257-3]
DR ABCD; O00257; 1 sequenced antibody.
DR Antibodypedia; 1793; 467 antibodies from 38 providers.
DR DNASU; 8535; -.
DR Ensembl; ENST00000269397.9; ENSP00000269397.4; ENSG00000141582.15. [O00257-1]
DR GeneID; 8535; -.
DR KEGG; hsa:8535; -.
DR MANE-Select; ENST00000269397.9; ENSP00000269397.4; NM_003655.3; NP_003646.2.
DR UCSC; uc002jxe.4; human. [O00257-1]
DR CTD; 8535; -.
DR DisGeNET; 8535; -.
DR GeneCards; CBX4; -.
DR HGNC; HGNC:1554; CBX4.
DR HPA; ENSG00000141582; Tissue enriched (bone).
DR MIM; 603079; gene.
DR neXtProt; NX_O00257; -.
DR OpenTargets; ENSG00000141582; -.
DR PharmGKB; PA26129; -.
DR VEuPathDB; HostDB:ENSG00000141582; -.
DR eggNOG; KOG2748; Eukaryota.
DR GeneTree; ENSGT00940000160081; -.
DR HOGENOM; CLU_043955_0_0_1; -.
DR InParanoid; O00257; -.
DR OMA; HPENGIP; -.
DR PhylomeDB; O00257; -.
DR TreeFam; TF106456; -.
DR PathwayCommons; O00257; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-HSA-4570464; SUMOylation of RNA binding proteins.
DR Reactome; R-HSA-4655427; SUMOylation of DNA methylation proteins.
DR Reactome; R-HSA-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR SignaLink; O00257; -.
DR SIGNOR; O00257; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 8535; 23 hits in 1086 CRISPR screens.
DR ChiTaRS; CBX4; human.
DR EvolutionaryTrace; O00257; -.
DR GenomeRNAi; 8535; -.
DR Pharos; O00257; Tchem.
DR PRO; PR:O00257; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O00257; protein.
DR Bgee; ENSG00000141582; Expressed in upper leg skin and 179 other tissues.
DR ExpressionAtlas; O00257; baseline and differential.
DR Genevisible; O00257; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031519; C:PcG protein complex; IDA:UniProtKB.
DR GO; GO:0035102; C:PRC1 complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IEA:Ensembl.
DR GO; GO:0051219; F:phosphoprotein binding; IEA:Ensembl.
DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl.
DR GO; GO:0032183; F:SUMO binding; IDA:MGI.
DR GO; GO:0061665; F:SUMO ligase activity; IDA:UniProtKB.
DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IBA:GO_Central.
DR InterPro; IPR043531; CBX4.
DR InterPro; IPR033773; CBX7_C.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR017984; Chromo_dom_subgr.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR023779; Chromodomain_CS.
DR PANTHER; PTHR46727; PTHR46727; 1.
DR Pfam; PF17218; CBX7_C; 1.
DR Pfam; PF00385; Chromo; 1.
DR PRINTS; PR00504; CHROMODOMAIN.
DR SMART; SM00298; CHROMO; 1.
DR SUPFAM; SSF54160; SSF54160; 1.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..560
FT /note="E3 SUMO-protein ligase CBX4"
FT /id="PRO_0000080206"
FT DOMAIN 11..69
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT REGION 1..539
FT /note="Interaction with BMI1"
FT REGION 1..75
FT /note="Involved in interaction with H3C15 and H3C1"
FT /evidence="ECO:0000269|PubMed:18927235"
FT REGION 92..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 217..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 531..556
FT /note="Involved in interaction with H3C15 and RNF2"
FT /evidence="ECO:0000269|PubMed:18927235"
FT REGION 540..560
FT /note="Interaction with RNF2"
FT COMPBIAS 92..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..335
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..404
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 149
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 497
FT /note="Phosphothreonine; by HIPK2"
FT /evidence="ECO:0000269|PubMed:17018294"
FT CROSSLNK 77
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 106
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 114
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 125
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 149
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:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 157
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 178
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 191
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 205
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 212
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 223
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 268
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 278
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 280
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 320
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 352
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 365
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 494
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000269|PubMed:15592428"
FT CROSSLNK 494
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 127..396
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_041599"
FT MUTAGEN 16
FT /note="I->F: Reduced interaction with H3C15, H3C1 and
FT RNF2."
FT /evidence="ECO:0000269|PubMed:18927235"
FT MUTAGEN 434
FT /note="S->A: Abolishes interaction with YWHAZ and YWHAE;
FT impairs interaction with PCGF6 and BMI1; no effect on
FT interaction with RNF2."
FT /evidence="ECO:0000269|PubMed:21282530"
FT MUTAGEN 494
FT /note="K->R: No effect on ZNF131 sumoylation."
FT /evidence="ECO:0000269|PubMed:22467880"
FT MUTAGEN 497
FT /note="T->A: Small decrease in ZNF131 sumoylation."
FT /evidence="ECO:0000269|PubMed:22467880"
FT CONFLICT 137..138
FT /note="Missing (in Ref. 1; AAB80718)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="P -> R (in Ref. 1; AAB80718)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="P -> R (in Ref. 1; AAB80718 and 5; AAB62734)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="C -> S (in Ref. 1; AAB80718 and 5; AAB62734)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="T -> S (in Ref. 1; AAB80718 and 5; AAB62734)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="V -> VAA (in Ref. 3; ACA49234)"
FT /evidence="ECO:0000305"
FT STRAND 13..22
FT /evidence="ECO:0007829|PDB:3I8Z"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:3I8Z"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:3I8Z"
FT STRAND 41..44
FT /evidence="ECO:0007829|PDB:3I8Z"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:3I8Z"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:3I8Z"
SQ SEQUENCE 560 AA; 61368 MW; DF5C8C4C0CCB1F31 CRC64;
MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSPKYN TWEPEENILD PRLLIAFQNR
ERQEQLMGYR KRGPKPKPLV VQVPTFARRS NVLTGLQDSS TDNRAKLDLG AQGKGQGHQY
ELNSKKHHQY QPHSKERAGK PPPPGKSGKY YYQLNSKKHH PYQPDPKMYD LQYQGGHKEA
PSPTCPDLGA KSHPPDKWAQ GAGAKGYLGA VKPLAGAAGA PGKGSEKGPP NGMMPAPKEA
VTGNGIGGKM KIVKNKNKNG RIVIVMSKYM ENGMQAVKIK SGEVAEGEAR SPSHKKRAAD
ERHPPADRTF KKAAGAEEKK VEAPPKRREE EVSGVSDPQP QDAGSRKLSP TKEAFGEQPL
QLTTKPDLLA WDPARNTHPP SHHPHPHPHH HHHHHHHHHH AVGLNLSHVR KRCLSETHGE
REPCKKRLTA RSISTPTCLG GSPAAERPAD LPPAAALPQP EVILLDSDLD EPIDLRCVKT
RSEAGEPPSS LQVKPETPAS AAVAVAAAAA PTTTAEKPPA EAQDEPAESL SEFKPFFGNI
IITDVTANCL TVTFKEYVTV
