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 27-MAR-2024, entry version 214. 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 UBIQUITINATION, AND DEUBIQUITINATION BY USP26. RX PubMed=28839133; DOI=10.1038/s41467-017-00301-4; RA Ning B., Zhao W., Qian C., Liu P., Li Q., Li W., Wang R.F.; RT "USP26 functions as a negative regulator of cellular reprogramming by RT stabilising PRC1 complex components."; RL Nat. Commun. 8:349-349(2017). RN [27] 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 [28] 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 [29] 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 [30] 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=3; 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: Ubiquitinated. Ubiquitination regulates the function of the CC Polycomb group (PcG) multiprotein PRC1-like complex. Deubiquitinated by CC USP26. {ECO:0000269|PubMed:28839133}. 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; 214. DR ComplexPortal; CPX-2594; Polycomb repressive complex 1, RING1-PCGF2-CBX4-PHC1 variant. DR ComplexPortal; CPX-2613; Polycomb repressive complex 1, RING1-PCGF2-CBX4-PHC2 variant. DR ComplexPortal; CPX-2615; Polycomb repressive complex 1, RING1-PCGF2-CBX4-PHC3 variant. DR ComplexPortal; CPX-7505; Polycomb repressive complex 1, RING1-PCGF4-CBX4-PHC1 variant. DR ComplexPortal; CPX-7506; Polycomb repressive complex 1, RING1-PCGF4-CBX4-PHC2 variant. DR ComplexPortal; CPX-7508; Polycomb repressive complex 1, RING1-PCGF4-CBX4-PHC3 variant. DR ComplexPortal; CPX-7524; Polycomb repressive complex 1, RING2-PCGF2-CBX4-PHC1 variant. DR ComplexPortal; CPX-7525; Polycomb repressive complex 1, RING2-PCGF2-CBX4-PHC3 variant. DR ComplexPortal; CPX-7526; Polycomb repressive complex 1, RING2-PCGF2-CBX4-PHC2 variant. DR ComplexPortal; CPX-7545; Polycomb repressive complex 1, RING2-PCGF4-CBX4-PHC1 variant. DR ComplexPortal; CPX-7546; Polycomb repressive complex 1, RING2-PCGF4-CBX4-PHC2 variant. DR ComplexPortal; CPX-7547; Polycomb repressive complex 1, RING2-PCGF4-CBX4-PHC3 variant. 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; 9606-ENSP00000269397; -. DR PeptideAtlas; O00257; -. DR ProteomicsDB; 47811; -. [O00257-1] DR ProteomicsDB; 47812; -. [O00257-3] DR Pumba; O00257; -. DR ABCD; O00257; 1 sequenced antibody. DR Antibodypedia; 1793; 516 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 AGR; HGNC:1554; -. 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; CLSEPHG; -. DR OrthoDB; 75895at2759; -. 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; 28 hits in 1169 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 181 other cell types or tissues. DR ExpressionAtlas; O00257; baseline and differential. 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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0016925; P:protein sumoylation; IBA:GO_Central. DR CDD; cd18645; CD_Cbx4; 1. DR Gene3D; 2.40.50.40; -; 1. DR IDEAL; IID00688; -. 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; E3 SUMO-PROTEIN LIGASE CBX4; 1. DR PANTHER; PTHR46727:SF1; E3 SUMO-PROTEIN LIGASE CBX4; 1. DR Pfam; PF17218; CBX7_C; 1. DR Pfam; PF00385; Chromo; 1. DR PRINTS; PR00504; CHROMODOMAIN. DR SMART; SM00298; CHROMO; 1. DR SUPFAM; SSF54160; Chromo domain-like; 1. DR PROSITE; PS00598; CHROMO_1; 1. DR PROSITE; PS50013; CHROMO_2; 1. DR Genevisible; O00257; HS. 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 //