CBX4_MOUSE
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 03-AUG-2022, entry version 168.
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}.
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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 AlphaFoldDB; O55187; -.
DR BMRB; O55187; -.
DR SMR; O55187; -.
DR BioGRID; 198537; 37.
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 ProteomicsDB; 265570; -. [O55187-1]
DR ProteomicsDB; 265571; -. [O55187-2]
DR Antibodypedia; 1793; 467 antibodies from 38 providers.
DR DNASU; 12418; -.
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 VEuPathDB; HostDB:ENSMUSG00000039989; -.
DR eggNOG; KOG2748; Eukaryota.
DR GeneTree; ENSGT00940000160081; -.
DR HOGENOM; CLU_043955_0_0_1; -.
DR InParanoid; O55187; -.
DR OMA; HPENGIP; -.
DR OrthoDB; 1628171at2759; -.
DR TreeFam; TF106456; -.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
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; 3 hits in 79 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 238 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 cis-regulatory region 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 REGION 125..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 216..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..336
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..399
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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
