ID CBX4_MOUSE Reviewed; 551 AA. AC O55187; Q149G5; Q149G6; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 12-DEC-2006, sequence version 2. DT 10-FEB-2021, entry version 162. DE RecName: Full=E3 SUMO-protein ligase CBX4; DE EC=2.3.2.-; DE AltName: Full=Chromobox protein homolog 4; DE AltName: Full=E3 SUMO-protein transferase CBX4 {ECO:0000305}; DE AltName: Full=Polycomb 2 homolog; DE Short=Pc2; DE Short=mPc2; GN Name=Cbx4; Synonyms=Pc2; 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 [MRNA] (ISOFORM 1). RX PubMed=9367786; DOI=10.1006/jmbi.1997.1372; RA Alkema M.J., Jacobs J., Voncken J.W., Jenkins N.A., Copeland N.G., RA Satijn D.P.E., Otte A.P., Berns A., van Lohuizen M.; RT "MPc2, a new murine homolog of the Drosophila polycomb protein is a member RT of the mouse polycomb transcriptional repressor complex."; RL J. Mol. Biol. 273:993-1003(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [3] RP FUNCTION, AND INTERACTION WITH HISTONE H3K9ME3 AND SSRNA. RX PubMed=16537902; DOI=10.1128/mcb.26.7.2560-2569.2006; RA Bernstein E., Duncan E.M., Masui O., Gil J., Heard E., Allis C.D.; RT "Mouse polycomb proteins bind differentially to methylated histone H3 and RT RNA and are enriched in facultative heterochromatin."; RL Mol. Cell. Biol. 26:2560-2569(2006). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Spleen; 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 [5] RP INTERACTION WITH RNF2, AND 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 [6] RP INTERACTION WITH CHTOP. RX PubMed=22872859; DOI=10.1074/mcp.m112.017194; RA Fanis P., Gillemans N., Aghajanirefah A., Pourfarzad F., Demmers J., RA Esteghamat F., Vadlamudi R.K., Grosveld F., Philipsen S., van Dijk T.B.; RT "Five friends of methylated chromatin target of protein-arginine- RT methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation RT to desumoylation."; RL Mol. Cell. Proteomics 11:1263-1273(2012). CC -!- FUNCTION: E3 SUMO-protein ligase which facilitates SUMO1 conjugation by CC UBE2I. Involved in the sumoylation of HNRNPK, a p53/TP53 CC transcriptional coactivator, hence indirectly regulates p53/TP53 CC transcriptional activation resulting in p21/CDKN1A expression. CC {ECO:0000250|UniProtKB:O00257}. 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 (By similarity). PcG PRC1 complex acts via chromatin CC remodeling and modification of histones; it mediates monoubiquitination CC of histone H2A 'Lys-119', rendering chromatin heritably changed in its CC expressibility (By similarity). Binds to histone H3 trimethylated at CC 'Lys-9' (H3K9me3) (PubMed:16537902). Plays a role in the lineage CC differentiation of the germ layers in embryonic development CC (PubMed:22226355). {ECO:0000250|UniProtKB:O00257, CC ECO:0000269|PubMed:16537902, ECO:0000269|PubMed:22226355}. CC -!- PATHWAY: Protein modification; protein sumoylation. CC -!- SUBUNIT: Interacts with SUV39H1 and HIPK2 (By similarity). Interacts CC with CSNK2B (By similarity). Component of a PRC1-like complex (By CC similarity). The composition of the PRC1 complex differs between the CC PRC1 complex in pluripotent embryonic stem cells containing RNF2, CBX7 CC and PCGF2, and the PRC1 complex in differentiating cells containing CC RNF2, CBX2, CBX4 and BMI1 (PubMed:22226355). Interacts with RNF2 CC (PubMed:22226355). Interacts (via chromodomain) with histone H3K9Me3 CC and single-stranded RNA (ssRNA) (PubMed:16537902). Interacts with CHTOP CC (PubMed:22872859). May interact with H3C15 and H3C1 (By similarity). CC Interacts with PRDM1 (By similarity). {ECO:0000250|UniProtKB:O00257, CC ECO:0000269|PubMed:16537902, ECO:0000269|PubMed:22226355, CC ECO:0000269|PubMed:22872859}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O00257}. Nucleus CC speckle {ECO:0000250|UniProtKB:O00257}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O55187-1; Sequence=Displayed; CC Name=2; CC IsoId=O55187-2; Sequence=VSP_022009; CC -!- TISSUE SPECIFICITY: Expressed in embryoid bodies. CC {ECO:0000269|PubMed:22226355}. CC -!- DOMAIN: The polyhistidine repeat may act as a targeting signal to CC nuclear speckles. {ECO:0000250}. 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; U63387; AAB96874.1; -; mRNA. DR EMBL; BC117801; AAI17802.1; -; mRNA. DR EMBL; BC117802; AAI17803.1; -; mRNA. DR CCDS; CCDS25710.1; -. [O55187-1] DR RefSeq; NP_031651.2; NM_007625.2. [O55187-1] DR BMRB; O55187; -. DR SMR; O55187; -. DR BioGRID; 198537; 35. DR IntAct; O55187; 20. DR STRING; 10090.ENSMUSP00000026665; -. DR iPTMnet; O55187; -. DR PhosphoSitePlus; O55187; -. DR EPD; O55187; -. DR MaxQB; O55187; -. DR PaxDb; O55187; -. DR PeptideAtlas; O55187; -. DR PRIDE; O55187; -. DR Antibodypedia; 1793; 437 antibodies. DR Ensembl; ENSMUST00000026665; ENSMUSP00000026665; ENSMUSG00000039989. [O55187-1] DR GeneID; 12418; -. DR KEGG; mmu:12418; -. DR UCSC; uc007mpv.2; mouse. [O55187-1] DR CTD; 8535; -. DR MGI; MGI:1195985; Cbx4. DR eggNOG; KOG2748; Eukaryota. DR GeneTree; ENSGT00940000160081; -. DR HOGENOM; CLU_043955_0_0_1; -. DR InParanoid; O55187; -. DR OMA; PLCRERE; -. DR OrthoDB; 1628171at2759; -. DR TreeFam; TF106456; -. DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-MMU-3899300; SUMOylation of transcription cofactors. DR Reactome; R-MMU-4551638; SUMOylation of chromatin organization proteins. DR Reactome; R-MMU-4570464; SUMOylation of RNA binding proteins. DR Reactome; R-MMU-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known. DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription. DR UniPathway; UPA00886; -. DR BioGRID-ORCS; 12418; 1 hit in 20 CRISPR screens. DR ChiTaRS; Cbx4; mouse. DR PRO; PR:O55187; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; O55187; protein. DR Bgee; ENSMUSG00000039989; Expressed in olfactory epithelium and 290 other tissues. DR Genevisible; O55187; MM. DR GO; GO:0016604; C:nuclear body; IDA:MGI. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0031519; C:PcG protein complex; ISS:UniProtKB. DR GO; GO:0035102; C:PRC1 complex; ISS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0051219; F:phosphoprotein binding; IPI:MGI. DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0032183; F:SUMO binding; IDA:MGI. DR GO; GO:0061665; F:SUMO ligase activity; ISO:MGI. DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI. DR GO; GO:0016925; P:protein sumoylation; IMP:MGI. 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 Acetylation; Alternative splicing; Chromatin regulator; Isopeptide bond; KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1..551 FT /note="E3 SUMO-protein ligase CBX4" FT /id="PRO_0000080207" FT DOMAIN 11..69 FT /note="Chromo" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053" FT COMPBIAS 383..395 FT /note="Poly-His" FT MOD_RES 149 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:O00257" FT MOD_RES 182 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00257" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 77 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 106 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 114 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 125 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 149 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 157 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 167 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 178 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 191 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 205 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 212 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 223 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 249 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 268 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 278 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 280 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 321 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 353 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 366 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00257" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000250" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:O00257" FT VAR_SEQ 1..66 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_022009" FT CONFLICT 77 FT /note="K -> N (in Ref. 1; AAB96874)" FT /evidence="ECO:0000305" FT CONFLICT 144..145 FT /note="PG -> AR (in Ref. 1; AAB96874)" FT /evidence="ECO:0000305" SQ SEQUENCE 551 AA; 60523 MW; 382F8305FD803CF3 CRC64; MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSPKYN TWEPEENILD PRLLIAFQNR ERQEQLMGYR KRGPKPKPLV VQVPTFARRS NVLTGLQDSS ADNRAKLELG TQGKGQGHQY ELNSKKHHQY QPHSKERSGK PPPPGKSGKY YYQLNSKKHH PYQPDPKMYD LQYQGGHKEA PSPTCPDLGT KSHPPDKWAH GAAAKGYLGA VKPLGGGAGA PGKGSEKGPP NGMTPAPKEA VTGNGIGGKM KIVKNKNKNG RIVIVMSKYM ENGMQAVKIK SGEAAEGEAR SPSHKKRAAE ERHPQGDRTF KKAAGASEEK KAEVPCKRRE EEALVSGDAQ PQDLGSRKLS PTKEAFGEQP LQLTTKPDLL AWDPARSSHP PAHHHHHHHH HHHHHTVGLN LSHARKRCLS ETHGEREPCK KRLTARSIST PTCLGGSPVS EHPANVSPTA ASLPQPEVIL LDSDLDEPID LRCVKMRSDA GEPPSTLQVK PEAPAVAAVV APAPASEKPP AEAQEEPVEP LSEFKPFFGN IIITDVTANC LTVTFKEYVT V //