CBX6_HUMAN
ID CBX6_HUMAN Reviewed; 412 AA.
AC O95503; A8KAH0; Q96EM5;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Chromobox protein homolog 6;
GN Name=CBX6;
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 [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Uterus;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [6]
RP FUNCTION, INTERACTION WITH H3C15; H3C1 AND RNF2, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, AND 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 [7]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP IDENTIFICATION IN A PRC1-LIKE COMPLEX, AND INTERACTION WITH RING1; RNF2;
RP PCGF1; PCGF2; PCGF3; BMI1; PCGF5 AND PCGF6.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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 [9]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 8-65 IN COMPLEXES WITH H3K9 AND
RP H3K27 PEPTIDES.
RX PubMed=21047797; DOI=10.1074/jbc.m110.191411;
RA Kaustov L., Ouyang H., Amaya M., Lemak A., Nady N., Duan S., Wasney G.A.,
RA Li Z., Vedadi M., Schapira M., Min J., Arrowsmith C.H.;
RT "Recognition and specificity determinants of the human cbx chromodomains.";
RL J. Biol. Chem. 286:521-529(2011).
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:21282530). 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. Possibly contributes to the target selectivity of the
CC PRC1 complex by binding specific regions of chromatin
CC (PubMed:18927235). Recruitment to chromatin might occur in an H3K27me3-
CC independent fashion (By similarity). May have a PRC1-independent
CC function in embryonic stem cells (By similarity).
CC {ECO:0000250|UniProtKB:Q9DBY5, ECO:0000269|PubMed:18927235,
CC ECO:0000269|PubMed:21282530}.
CC -!- SUBUNIT: Component of a PRC1-like complex (PubMed:21282530). Distinct
CC PRC1-like core complexes are composed of a RING1 subunit (RING1B or
CC RING1A), one of the six PCGF proteins (PCGF1-6), one PHC protein (PHC1-
CC 3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8)
CC (PubMed:21282530). Interacts with PCGF1, PCGF2, PCGF3, BMI1, PCGF5,
CC PCGF6, RING1 and RNF2 (PubMed:21282530, PubMed:18927235). May interact
CC with H3C15 and H3C1 (PubMed:18927235). Interacts (via chromodomain)
CC with single-stranded RNA (ssRNA) (By similarity).
CC {ECO:0000250|UniProtKB:Q9DBY5, ECO:0000269|PubMed:18927235,
CC ECO:0000269|PubMed:21282530}.
CC -!- INTERACTION:
CC O95503; P35226: BMI1; NbExp=8; IntAct=EBI-3951758, EBI-2341576;
CC O95503; O14901: KLF11; NbExp=3; IntAct=EBI-3951758, EBI-948266;
CC O95503; Q9HCE1: MOV10; NbExp=2; IntAct=EBI-3951758, EBI-1055820;
CC O95503; P35227: PCGF2; NbExp=3; IntAct=EBI-3951758, EBI-2129767;
CC O95503; Q3KNV8: PCGF3; NbExp=2; IntAct=EBI-3951758, EBI-2339807;
CC O95503; Q06587: RING1; NbExp=6; IntAct=EBI-3951758, EBI-752313;
CC O95503; Q99496: RNF2; NbExp=7; IntAct=EBI-3951758, EBI-722416;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18927235}. Chromosome
CC {ECO:0000269|PubMed:18927235}. Note=Uniformely distributed in the
CC nucleoplasm (PubMed:18927235). Localizes to the inactivated X
CC chromosome in females (By similarity). {ECO:0000250|UniProtKB:Q9DBY5,
CC ECO:0000269|PubMed:18927235}.
CC -!- DEVELOPMENTAL STAGE: Expressed during interphase and metaphase.
CC {ECO:0000269|PubMed:18927235}.
CC -!- MISCELLANEOUS: The human orthologuous proteins of Drosophila Polycomb
CC group protein Pc, CBX2, CBX4, CBX6, CBX7 and CBX8, show distinct
CC nuclear localizations, contribute differently to transcriptional
CC repression, and appear to be part of distinct PRC1-like protein
CC complexes.
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DR EMBL; AK293035; BAF85724.1; -; mRNA.
DR EMBL; AL008583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60276.1; -; Genomic_DNA.
DR EMBL; BC012111; AAH12111.1; -; mRNA.
DR EMBL; BC064900; AAH64900.1; -; mRNA.
DR CCDS; CCDS13980.1; -.
DR RefSeq; NP_001290423.1; NM_001303494.1.
DR RefSeq; NP_055107.3; NM_014292.4.
DR PDB; 3GV6; X-ray; 1.76 A; A=8-65.
DR PDB; 3I90; X-ray; 2.00 A; A/B=9-59.
DR PDBsum; 3GV6; -.
DR PDBsum; 3I90; -.
DR AlphaFoldDB; O95503; -.
DR SMR; O95503; -.
DR BioGRID; 117028; 289.
DR DIP; DIP-48605N; -.
DR IntAct; O95503; 91.
DR MINT; O95503; -.
DR STRING; 9606.ENSP00000384490; -.
DR BindingDB; O95503; -.
DR ChEMBL; CHEMBL3779762; -.
DR iPTMnet; O95503; -.
DR PhosphoSitePlus; O95503; -.
DR BioMuta; CBX6; -.
DR EPD; O95503; -.
DR jPOST; O95503; -.
DR MassIVE; O95503; -.
DR MaxQB; O95503; -.
DR PaxDb; O95503; -.
DR PeptideAtlas; O95503; -.
DR PRIDE; O95503; -.
DR ProteomicsDB; 50932; -.
DR Antibodypedia; 272; 258 antibodies from 33 providers.
DR DNASU; 23466; -.
DR Ensembl; ENST00000407418.8; ENSP00000384490.3; ENSG00000183741.12.
DR GeneID; 23466; -.
DR KEGG; hsa:23466; -.
DR MANE-Select; ENST00000407418.8; ENSP00000384490.3; NM_014292.5; NP_055107.3.
DR UCSC; uc003awl.4; human.
DR CTD; 23466; -.
DR DisGeNET; 23466; -.
DR GeneCards; CBX6; -.
DR HGNC; HGNC:1556; CBX6.
DR HPA; ENSG00000183741; Tissue enhanced (brain).
DR MIM; 617438; gene.
DR neXtProt; NX_O95503; -.
DR OpenTargets; ENSG00000183741; -.
DR PharmGKB; PA26131; -.
DR VEuPathDB; HostDB:ENSG00000183741; -.
DR eggNOG; KOG2748; Eukaryota.
DR GeneTree; ENSGT00940000154405; -.
DR InParanoid; O95503; -.
DR OMA; FGAFAMY; -.
DR OrthoDB; 1628171at2759; -.
DR PhylomeDB; O95503; -.
DR TreeFam; TF106456; -.
DR PathwayCommons; O95503; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
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; O95503; -.
DR BioGRID-ORCS; 23466; 8 hits in 1080 CRISPR screens.
DR ChiTaRS; CBX6; human.
DR EvolutionaryTrace; O95503; -.
DR GenomeRNAi; 23466; -.
DR Pharos; O95503; Tchem.
DR PRO; PR:O95503; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O95503; protein.
DR Bgee; ENSG00000183741; Expressed in Brodmann (1909) area 10 and 197 other tissues.
DR ExpressionAtlas; O95503; baseline and differential.
DR Genevisible; O95503; HS.
DR GO; GO:0000792; C:heterochromatin; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031519; C:PcG protein complex; IDA:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR IDEAL; IID00362; -.
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 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; Chromatin regulator; Chromosome; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..412
FT /note="Chromobox protein homolog 6"
FT /id="PRO_0000080210"
FT DOMAIN 11..69
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT REGION 127..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MUTAGEN 16
FT /note="I->F: Reduced interaction with H3C15 and H3C1."
FT /evidence="ECO:0000269|PubMed:18927235"
FT CONFLICT 292
FT /note="P -> L (in Ref. 4; AAH12111)"
FT /evidence="ECO:0000305"
FT STRAND 9..22
FT /evidence="ECO:0007829|PDB:3GV6"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:3GV6"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:3GV6"
FT STRAND 41..44
FT /evidence="ECO:0007829|PDB:3GV6"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:3GV6"
FT HELIX 51..62
FT /evidence="ECO:0007829|PDB:3GV6"
SQ SEQUENCE 412 AA; 43898 MW; 50C69233B9ADEEA3 CRC64;
MELSAVGERV FAAESIIKRR IRKGRIEYLV KWKGWAIKYS TWEPEENILD SRLIAAFEQK
ERERELYGPK KRGPKPKTFL LKARAQAEAL RISDVHFSVK PSASASSPKL HSSAAVHRLK
KDIRRCHRMS RRPLPRPDPQ GGSPGLRPPI SPFSETVRII NRKVKPREPK RNRIILNLKV
IDKGAGGGGA GQGAGALARP KVPSRNRVIG KSKKFSESVL RTQIRHMKFG AFALYKPPPA
PLVAPSPGKA EASAPGPGLL LAAPAAPYDA RSSGSSGCPS PTPQSSDPDD TPPKLLPETV
SPSAPSWREP EVLDLSLPPE SAATSKRAPP EVTAAAGPAP PTAPEPAGAS SEPEAGDWRP
EMSPCSNVVV TDVTSNLLTV TIKEFCNPED FEKVAAGVAG AAGGGGSIGA SK
