Full text data of CBX3
CBX3
[Confidence: low (only semi-automatic identification from reviews)]
Chromobox protein homolog 3 (HECH; Heterochromatin protein 1 homolog gamma; HP1 gamma; Modifier 2 protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Chromobox protein homolog 3 (HECH; Heterochromatin protein 1 homolog gamma; HP1 gamma; Modifier 2 protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13185
ID CBX3_HUMAN Reviewed; 183 AA.
AC Q13185; Q96CD7; Q99409; Q9BVS3; Q9P0Z6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 4.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Chromobox protein homolog 3;
DE AltName: Full=HECH;
DE AltName: Full=Heterochromatin protein 1 homolog gamma;
DE Short=HP1 gamma;
DE AltName: Full=Modifier 2 protein;
GN Name=CBX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-183.
RX PubMed=8663349; DOI=10.1074/jbc.271.25.14653;
RA Ye Q., Worman H.J.;
RT "Interaction between an integral protein of the nuclear envelope inner
RT membrane and human chromodomain proteins homologous to Drosophila
RT HP1.";
RL J. Biol. Chem. 271:14653-14656(1996).
RN [2]
RP SEQUENCE REVISION.
RA Ye Q., Worman H.J.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-183, AND PHOSPHORYLATION BY PIM1.
RX PubMed=10664448; DOI=10.1016/S0014-5793(00)01105-4;
RA Koike N., Maita H., Taira T., Ariga H., Iguchi-Ariga S.M.M.;
RT "Identification of heterochromatin protein 1 (HP1) as a
RT phosphorylation target by Pim-1 kinase and the effect of
RT phosphorylation on the transcriptional repression function of HP1.";
RL FEBS Lett. 467:17-21(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen J.H., Luo W.Q., Hu S.N., Zhou H.J., Huang X.W., Zhou Y.,
RA Yuan J.G., Qiang B.Q.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 160-171, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP INTERACTION WITH LBR AND CBX5.
RX PubMed=9169472; DOI=10.1074/jbc.272.23.14983;
RA Ye Q., Callebaut I., Pezhman A., Courvalin J.-C., Worman H.J.;
RT "Domain-specific interactions of human HP1-type chromodomain proteins
RT and inner nuclear membrane protein LBR.";
RL J. Biol. Chem. 272:14983-14989(1997).
RN [8]
RP INTERACTION WITH INCENP.
RX PubMed=9864353; DOI=10.1083/jcb.143.7.1763;
RA Ainsztein A.M., Kandels-Lewis S.E., Mackay A.M., Earnshaw W.C.;
RT "INCENP centromere and spindle targeting: identification of essential
RT conserved motifs and involvement of heterochromatin protein HP1.";
RL J. Cell Biol. 143:1763-1774(1998).
RN [9]
RP INTERACTION WITH SP100.
RX PubMed=9636146; DOI=10.1073/pnas.95.13.7316;
RA Seeler J.-S., Marchio A., Sitterlin D., Transy C., Dejean A.;
RT "Interaction of SP100 with HP1 proteins: a link between the
RT promyelocytic leukemia-associated nuclear bodies and the chromatin
RT compartment.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:7316-7321(1998).
RN [10]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=10460410; DOI=10.1007/s004120050372;
RA Minc E., Allory Y., Worman H.J., Courvalin J.-C., Buendia B.;
RT "Localization and phosphorylation of HP1 proteins during the cell
RT cycle in mammalian cells.";
RL Chromosoma 108:220-234(1999).
RN [11]
RP INTERACTION WITH TRIM28.
RX PubMed=10330177;
RA Ryan R.F., Schultz D.C., Ayyanathan K., Singh P.B., Friedman J.R.,
RA Fredericks W.J., Rauscher F.J. III;
RT "KAP-1 corepressor protein interacts and colocalizes with
RT heterochromatic and euchromatic HP1 proteins: a potential role for
RT Kruppel-associated box-zinc finger proteins in heterochromatin-
RT mediated gene silencing.";
RL Mol. Cell. Biol. 19:4366-4378(1999).
RN [12]
RP INTERACTION WITH HISTONE H3 LYS-9.
RX PubMed=11242053; DOI=10.1038/35065132;
RA Lachner M., O'Carroll D., Rea S., Mechtler K., Jenuwein T.;
RT "Methylation of histone H3 lysine 9 creates a binding site for HP1
RT proteins.";
RL Nature 410:116-120(2001).
RN [13]
RP IDENTIFICATION IN COMPLEX WITH E2F6; TFDP1; MAX; MGA; BAT8; EUHMTASE1;
RP RING1; RNF2; MBLR; L3MBTL2 AND YAF2.
RX PubMed=12004135; DOI=10.1126/science.1069861;
RA Ogawa H., Ishiguro K., Gaubatz S., Livingston D.M., Nakatani Y.;
RT "A complex with chromatin modifiers that occupies E2F- and Myc-
RT responsive genes in G0 cells.";
RL Science 296:1132-1136(2002).
RN [14]
RP INTERACTION WITH MIS12 AND DSN1.
RX PubMed=15502821; DOI=10.1038/ncb1187;
RA Obuse C., Iwasaki O., Kiyomitsu T., Goshima G., Toyoda Y.,
RA Yanagida M.;
RT "A conserved Mis12 centromere complex is linked to heterochromatic HP1
RT and outer kinetochore protein Zwint-1.";
RL Nat. Cell Biol. 6:1135-1141(2004).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95 AND SER-176, AND MASS
RP SPECTROMETRY.
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-10; LYS-44 AND LYS-50, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [21]
RP INTERACTION WITH CHAMP1 AND POGZ.
RX PubMed=20850016; DOI=10.1016/j.cell.2010.08.020;
RA Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S.,
RA Butter F., Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G.,
RA Mann M.;
RT "Quantitative interaction proteomics and genome-wide profiling of
RT epigenetic histone marks and their readers.";
RL Cell 142:967-980(2010).
RN [22]
RP INTERACTION WITH ASXL1.
RX PubMed=19880879; DOI=10.1074/jbc.M109.065862;
RA Lee S.W., Cho Y.S., Na J.M., Park U.H., Kang M., Kim E.J., Um S.J.;
RT "ASXL1 represses retinoic acid receptor-mediated transcription through
RT associating with HP1 and LSD1.";
RL J. Biol. Chem. 285:18-29(2010).
RN [23]
RP INTERACTION WITH POGZ.
RX PubMed=20562864; DOI=10.1038/ncb2075;
RA Nozawa R.S., Nagao K., Masuda H.T., Iwasaki O., Hirota T., Nozaki N.,
RA Kimura H., Obuse C.;
RT "Human POGZ modulates dissociation of HP1alpha from mitotic chromosome
RT arms through Aurora B activation.";
RL Nat. Cell Biol. 12:719-727(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93 AND SER-95, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-95; SER-97 AND
RP SER-99, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 29-86 IN COMPLEX WITH
RP PEPTIDE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex of chromobox homolog 3 (CBX3) [Homo
RT sapiens] and peptide.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Seems to be involved in transcriptional silencing in
CC heterochromatin-like complexes. Recognizes and binds histone H3
CC tails methylated at 'Lys-9', leading to epigenetic repression. May
CC contribute to the association of the heterochromatin with the
CC inner nuclear membrane through its interaction with lamin B
CC receptor (LBR). Involved in the formation of functional
CC kinetochore through interaction with MIS12 complex proteins.
CC -!- SUBUNIT: Binds directly to CHAF1A. Interacts with histone H3
CC methylated at 'Lys-9'. Part of the E2F6.com-1 complex in G0 phase
CC composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1,
CC RNF2, MBLR, L3MBTL2 and YAF2. Interacts with LBR, INCENP,
CC TRIM28/TIF1B, SUV420H1, SUV420H2 and SP100. Interacts with TIF1A
CC (By similarity). Interacts with MIS12 and DSN1. Can interact
CC directly with CBX5 via the chromoshadow domain. Interacts with
CC POGZ. Interacts with CHAMP1. Interacts with ASXL1.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-78176, EBI-78176;
CC Q9H2P0:ADNP; NbExp=2; IntAct=EBI-78176, EBI-1764854;
CC P68431:HIST1H3D; NbExp=5; IntAct=EBI-78176, EBI-79722;
CC Q14739:LBR; NbExp=4; IntAct=EBI-78176, EBI-1055147;
CC Q13263:TRIM28; NbExp=3; IntAct=EBI-78176, EBI-78139;
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential). Note=Associates with
CC euchromatin and is largely excluded from constitutive
CC heterochromatin. May be associated with microtubules and mitotic
CC poles during mitosis (Potential).
CC -!- PTM: Phosphorylated by PIM1. Phosphorylated during interphase and
CC possibly hyper-phosphorylated during mitosis.
CC -!- SIMILARITY: Contains 2 chromo domains.
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DR EMBL; U26312; AAB48101.1; -; mRNA.
DR EMBL; AB030905; BAA83340.1; -; mRNA.
DR EMBL; AF136630; AAF62370.1; -; mRNA.
DR EMBL; BC000954; AAH00954.1; -; mRNA.
DR EMBL; BC014380; AAH14380.1; -; mRNA.
DR RefSeq; NP_009207.2; NM_007276.4.
DR RefSeq; NP_057671.2; NM_016587.3.
DR RefSeq; XP_005249668.1; XM_005249611.1.
DR UniGene; Hs.381189; -.
DR PDB; 2L11; NMR; -; A=29-81.
DR PDB; 3DM1; X-ray; 2.40 A; A/C/E/G=29-86.
DR PDB; 3KUP; X-ray; 1.77 A; A/B/C/D=110-173.
DR PDB; 3TZD; X-ray; 1.81 A; A=29-81.
DR PDBsum; 2L11; -.
DR PDBsum; 3DM1; -.
DR PDBsum; 3KUP; -.
DR PDBsum; 3TZD; -.
DR ProteinModelPortal; Q13185; -.
DR SMR; Q13185; 29-81, 112-173.
DR DIP; DIP-5985N; -.
DR IntAct; Q13185; 47.
DR MINT; MINT-5002782; -.
DR STRING; 9606.ENSP00000336687; -.
DR PhosphoSite; Q13185; -.
DR DMDM; 116241284; -.
DR SWISS-2DPAGE; Q13185; -.
DR PaxDb; Q13185; -.
DR PeptideAtlas; Q13185; -.
DR PRIDE; Q13185; -.
DR DNASU; 11335; -.
DR Ensembl; ENST00000337620; ENSP00000336687; ENSG00000122565.
DR Ensembl; ENST00000396386; ENSP00000379670; ENSG00000122565.
DR GeneID; 11335; -.
DR KEGG; hsa:11335; -.
DR UCSC; uc003sxt.3; human.
DR CTD; 11335; -.
DR GeneCards; GC07P026207; -.
DR HGNC; HGNC:1553; CBX3.
DR HPA; CAB001973; -.
DR HPA; HPA004902; -.
DR MIM; 604477; gene.
DR neXtProt; NX_Q13185; -.
DR PharmGKB; PA26128; -.
DR eggNOG; NOG264487; -.
DR HOGENOM; HOG000220852; -.
DR HOVERGEN; HBG000400; -.
DR InParanoid; Q13185; -.
DR KO; K11586; -.
DR OMA; RESADKP; -.
DR OrthoDB; EOG7QRQWW; -.
DR PhylomeDB; Q13185; -.
DR ChiTaRS; CBX3; human.
DR EvolutionaryTrace; Q13185; -.
DR GeneWiki; CBX3; -.
DR GenomeRNAi; 11335; -.
DR NextBio; 43065; -.
DR PRO; PR:Q13185; -.
DR ArrayExpress; Q13185; -.
DR Bgee; Q13185; -.
DR CleanEx; HS_CBX3; -.
DR Genevestigator; Q13185; -.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; ISS:UniProtKB.
DR GO; GO:0031618; C:nuclear centromeric heterochromatin; ISS:UniProtKB.
DR GO; GO:0005719; C:nuclear euchromatin; IDA:UniProtKB.
DR GO; GO:0005637; C:nuclear inner membrane; NAS:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; NAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR017984; Chromo_dom_subgr.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR000953; Chromo_domain/shadow.
DR InterPro; IPR008251; Chromo_shadow_dom.
DR InterPro; IPR016197; Chromodomain-like.
DR InterPro; IPR023779; Chromodomain_CS.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF01393; Chromo_shadow; 1.
DR PRINTS; PR00504; CHROMODOMAIN.
DR SMART; SM00298; CHROMO; 2.
DR SMART; SM00300; ChSh; 1.
DR SUPFAM; SSF54160; SSF54160; 2.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromatin regulator; Complete proteome;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1 183 Chromobox protein homolog 3.
FT /FTId=PRO_0000080203.
FT DOMAIN 30 88 Chromo 1.
FT DOMAIN 121 179 Chromo 2; shadow subtype.
FT MOD_RES 10 10 N6-acetyllysine.
FT MOD_RES 44 44 N6-acetyllysine.
FT MOD_RES 50 50 N6-acetyllysine.
FT MOD_RES 93 93 Phosphoserine.
FT MOD_RES 95 95 Phosphoserine.
FT MOD_RES 97 97 Phosphoserine.
FT MOD_RES 99 99 Phosphoserine.
FT MOD_RES 176 176 Phosphoserine.
FT CONFLICT 111 111 A -> G (in Ref. 5; AAH14380).
FT CONFLICT 111 111 A -> V (in Ref. 4; AAF62370).
FT CONFLICT 130 130 T -> I (in Ref. 1; AAB48101 and 3;
FT BAA83340).
FT STRAND 29 41
FT STRAND 44 51
FT HELIX 56 58
FT STRAND 60 63
FT HELIX 64 66
FT HELIX 70 80
FT HELIX 116 119
FT STRAND 123 130
FT STRAND 137 142
FT STRAND 149 152
FT HELIX 153 159
FT HELIX 161 171
SQ SEQUENCE 183 AA; 20811 MW; 5928C63E0C93A76A CRC64;
MASNKTTLQK MGKKQNGKSK KVEEAEPEEF VVEKVLDRRV VNGKVEYFLK WKGFTDADNT
WEPEENLDCP ELIEAFLNSQ KAGKEKDGTK RKSLSDSESD DSKSKKKRDA ADKPRGFARG
LDPERIIGAT DSSGELMFLM KWKDSDEADL VLAKEANMKC PQIVIAFYEE RLTWHSCPED
EAQ
//
ID CBX3_HUMAN Reviewed; 183 AA.
AC Q13185; Q96CD7; Q99409; Q9BVS3; Q9P0Z6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 4.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Chromobox protein homolog 3;
DE AltName: Full=HECH;
DE AltName: Full=Heterochromatin protein 1 homolog gamma;
DE Short=HP1 gamma;
DE AltName: Full=Modifier 2 protein;
GN Name=CBX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-183.
RX PubMed=8663349; DOI=10.1074/jbc.271.25.14653;
RA Ye Q., Worman H.J.;
RT "Interaction between an integral protein of the nuclear envelope inner
RT membrane and human chromodomain proteins homologous to Drosophila
RT HP1.";
RL J. Biol. Chem. 271:14653-14656(1996).
RN [2]
RP SEQUENCE REVISION.
RA Ye Q., Worman H.J.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-183, AND PHOSPHORYLATION BY PIM1.
RX PubMed=10664448; DOI=10.1016/S0014-5793(00)01105-4;
RA Koike N., Maita H., Taira T., Ariga H., Iguchi-Ariga S.M.M.;
RT "Identification of heterochromatin protein 1 (HP1) as a
RT phosphorylation target by Pim-1 kinase and the effect of
RT phosphorylation on the transcriptional repression function of HP1.";
RL FEBS Lett. 467:17-21(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen J.H., Luo W.Q., Hu S.N., Zhou H.J., Huang X.W., Zhou Y.,
RA Yuan J.G., Qiang B.Q.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 160-171, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP INTERACTION WITH LBR AND CBX5.
RX PubMed=9169472; DOI=10.1074/jbc.272.23.14983;
RA Ye Q., Callebaut I., Pezhman A., Courvalin J.-C., Worman H.J.;
RT "Domain-specific interactions of human HP1-type chromodomain proteins
RT and inner nuclear membrane protein LBR.";
RL J. Biol. Chem. 272:14983-14989(1997).
RN [8]
RP INTERACTION WITH INCENP.
RX PubMed=9864353; DOI=10.1083/jcb.143.7.1763;
RA Ainsztein A.M., Kandels-Lewis S.E., Mackay A.M., Earnshaw W.C.;
RT "INCENP centromere and spindle targeting: identification of essential
RT conserved motifs and involvement of heterochromatin protein HP1.";
RL J. Cell Biol. 143:1763-1774(1998).
RN [9]
RP INTERACTION WITH SP100.
RX PubMed=9636146; DOI=10.1073/pnas.95.13.7316;
RA Seeler J.-S., Marchio A., Sitterlin D., Transy C., Dejean A.;
RT "Interaction of SP100 with HP1 proteins: a link between the
RT promyelocytic leukemia-associated nuclear bodies and the chromatin
RT compartment.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:7316-7321(1998).
RN [10]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=10460410; DOI=10.1007/s004120050372;
RA Minc E., Allory Y., Worman H.J., Courvalin J.-C., Buendia B.;
RT "Localization and phosphorylation of HP1 proteins during the cell
RT cycle in mammalian cells.";
RL Chromosoma 108:220-234(1999).
RN [11]
RP INTERACTION WITH TRIM28.
RX PubMed=10330177;
RA Ryan R.F., Schultz D.C., Ayyanathan K., Singh P.B., Friedman J.R.,
RA Fredericks W.J., Rauscher F.J. III;
RT "KAP-1 corepressor protein interacts and colocalizes with
RT heterochromatic and euchromatic HP1 proteins: a potential role for
RT Kruppel-associated box-zinc finger proteins in heterochromatin-
RT mediated gene silencing.";
RL Mol. Cell. Biol. 19:4366-4378(1999).
RN [12]
RP INTERACTION WITH HISTONE H3 LYS-9.
RX PubMed=11242053; DOI=10.1038/35065132;
RA Lachner M., O'Carroll D., Rea S., Mechtler K., Jenuwein T.;
RT "Methylation of histone H3 lysine 9 creates a binding site for HP1
RT proteins.";
RL Nature 410:116-120(2001).
RN [13]
RP IDENTIFICATION IN COMPLEX WITH E2F6; TFDP1; MAX; MGA; BAT8; EUHMTASE1;
RP RING1; RNF2; MBLR; L3MBTL2 AND YAF2.
RX PubMed=12004135; DOI=10.1126/science.1069861;
RA Ogawa H., Ishiguro K., Gaubatz S., Livingston D.M., Nakatani Y.;
RT "A complex with chromatin modifiers that occupies E2F- and Myc-
RT responsive genes in G0 cells.";
RL Science 296:1132-1136(2002).
RN [14]
RP INTERACTION WITH MIS12 AND DSN1.
RX PubMed=15502821; DOI=10.1038/ncb1187;
RA Obuse C., Iwasaki O., Kiyomitsu T., Goshima G., Toyoda Y.,
RA Yanagida M.;
RT "A conserved Mis12 centromere complex is linked to heterochromatic HP1
RT and outer kinetochore protein Zwint-1.";
RL Nat. Cell Biol. 6:1135-1141(2004).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95 AND SER-176, AND MASS
RP SPECTROMETRY.
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-10; LYS-44 AND LYS-50, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [21]
RP INTERACTION WITH CHAMP1 AND POGZ.
RX PubMed=20850016; DOI=10.1016/j.cell.2010.08.020;
RA Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S.,
RA Butter F., Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G.,
RA Mann M.;
RT "Quantitative interaction proteomics and genome-wide profiling of
RT epigenetic histone marks and their readers.";
RL Cell 142:967-980(2010).
RN [22]
RP INTERACTION WITH ASXL1.
RX PubMed=19880879; DOI=10.1074/jbc.M109.065862;
RA Lee S.W., Cho Y.S., Na J.M., Park U.H., Kang M., Kim E.J., Um S.J.;
RT "ASXL1 represses retinoic acid receptor-mediated transcription through
RT associating with HP1 and LSD1.";
RL J. Biol. Chem. 285:18-29(2010).
RN [23]
RP INTERACTION WITH POGZ.
RX PubMed=20562864; DOI=10.1038/ncb2075;
RA Nozawa R.S., Nagao K., Masuda H.T., Iwasaki O., Hirota T., Nozaki N.,
RA Kimura H., Obuse C.;
RT "Human POGZ modulates dissociation of HP1alpha from mitotic chromosome
RT arms through Aurora B activation.";
RL Nat. Cell Biol. 12:719-727(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93 AND SER-95, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-95; SER-97 AND
RP SER-99, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 29-86 IN COMPLEX WITH
RP PEPTIDE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the complex of chromobox homolog 3 (CBX3) [Homo
RT sapiens] and peptide.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Seems to be involved in transcriptional silencing in
CC heterochromatin-like complexes. Recognizes and binds histone H3
CC tails methylated at 'Lys-9', leading to epigenetic repression. May
CC contribute to the association of the heterochromatin with the
CC inner nuclear membrane through its interaction with lamin B
CC receptor (LBR). Involved in the formation of functional
CC kinetochore through interaction with MIS12 complex proteins.
CC -!- SUBUNIT: Binds directly to CHAF1A. Interacts with histone H3
CC methylated at 'Lys-9'. Part of the E2F6.com-1 complex in G0 phase
CC composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1,
CC RNF2, MBLR, L3MBTL2 and YAF2. Interacts with LBR, INCENP,
CC TRIM28/TIF1B, SUV420H1, SUV420H2 and SP100. Interacts with TIF1A
CC (By similarity). Interacts with MIS12 and DSN1. Can interact
CC directly with CBX5 via the chromoshadow domain. Interacts with
CC POGZ. Interacts with CHAMP1. Interacts with ASXL1.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-78176, EBI-78176;
CC Q9H2P0:ADNP; NbExp=2; IntAct=EBI-78176, EBI-1764854;
CC P68431:HIST1H3D; NbExp=5; IntAct=EBI-78176, EBI-79722;
CC Q14739:LBR; NbExp=4; IntAct=EBI-78176, EBI-1055147;
CC Q13263:TRIM28; NbExp=3; IntAct=EBI-78176, EBI-78139;
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential). Note=Associates with
CC euchromatin and is largely excluded from constitutive
CC heterochromatin. May be associated with microtubules and mitotic
CC poles during mitosis (Potential).
CC -!- PTM: Phosphorylated by PIM1. Phosphorylated during interphase and
CC possibly hyper-phosphorylated during mitosis.
CC -!- SIMILARITY: Contains 2 chromo domains.
CC -----------------------------------------------------------------------
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DR EMBL; U26312; AAB48101.1; -; mRNA.
DR EMBL; AB030905; BAA83340.1; -; mRNA.
DR EMBL; AF136630; AAF62370.1; -; mRNA.
DR EMBL; BC000954; AAH00954.1; -; mRNA.
DR EMBL; BC014380; AAH14380.1; -; mRNA.
DR RefSeq; NP_009207.2; NM_007276.4.
DR RefSeq; NP_057671.2; NM_016587.3.
DR RefSeq; XP_005249668.1; XM_005249611.1.
DR UniGene; Hs.381189; -.
DR PDB; 2L11; NMR; -; A=29-81.
DR PDB; 3DM1; X-ray; 2.40 A; A/C/E/G=29-86.
DR PDB; 3KUP; X-ray; 1.77 A; A/B/C/D=110-173.
DR PDB; 3TZD; X-ray; 1.81 A; A=29-81.
DR PDBsum; 2L11; -.
DR PDBsum; 3DM1; -.
DR PDBsum; 3KUP; -.
DR PDBsum; 3TZD; -.
DR ProteinModelPortal; Q13185; -.
DR SMR; Q13185; 29-81, 112-173.
DR DIP; DIP-5985N; -.
DR IntAct; Q13185; 47.
DR MINT; MINT-5002782; -.
DR STRING; 9606.ENSP00000336687; -.
DR PhosphoSite; Q13185; -.
DR DMDM; 116241284; -.
DR SWISS-2DPAGE; Q13185; -.
DR PaxDb; Q13185; -.
DR PeptideAtlas; Q13185; -.
DR PRIDE; Q13185; -.
DR DNASU; 11335; -.
DR Ensembl; ENST00000337620; ENSP00000336687; ENSG00000122565.
DR Ensembl; ENST00000396386; ENSP00000379670; ENSG00000122565.
DR GeneID; 11335; -.
DR KEGG; hsa:11335; -.
DR UCSC; uc003sxt.3; human.
DR CTD; 11335; -.
DR GeneCards; GC07P026207; -.
DR HGNC; HGNC:1553; CBX3.
DR HPA; CAB001973; -.
DR HPA; HPA004902; -.
DR MIM; 604477; gene.
DR neXtProt; NX_Q13185; -.
DR PharmGKB; PA26128; -.
DR eggNOG; NOG264487; -.
DR HOGENOM; HOG000220852; -.
DR HOVERGEN; HBG000400; -.
DR InParanoid; Q13185; -.
DR KO; K11586; -.
DR OMA; RESADKP; -.
DR OrthoDB; EOG7QRQWW; -.
DR PhylomeDB; Q13185; -.
DR ChiTaRS; CBX3; human.
DR EvolutionaryTrace; Q13185; -.
DR GeneWiki; CBX3; -.
DR GenomeRNAi; 11335; -.
DR NextBio; 43065; -.
DR PRO; PR:Q13185; -.
DR ArrayExpress; Q13185; -.
DR Bgee; Q13185; -.
DR CleanEx; HS_CBX3; -.
DR Genevestigator; Q13185; -.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; ISS:UniProtKB.
DR GO; GO:0031618; C:nuclear centromeric heterochromatin; ISS:UniProtKB.
DR GO; GO:0005719; C:nuclear euchromatin; IDA:UniProtKB.
DR GO; GO:0005637; C:nuclear inner membrane; NAS:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; NAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR017984; Chromo_dom_subgr.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR000953; Chromo_domain/shadow.
DR InterPro; IPR008251; Chromo_shadow_dom.
DR InterPro; IPR016197; Chromodomain-like.
DR InterPro; IPR023779; Chromodomain_CS.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF01393; Chromo_shadow; 1.
DR PRINTS; PR00504; CHROMODOMAIN.
DR SMART; SM00298; CHROMO; 2.
DR SMART; SM00300; ChSh; 1.
DR SUPFAM; SSF54160; SSF54160; 2.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromatin regulator; Complete proteome;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1 183 Chromobox protein homolog 3.
FT /FTId=PRO_0000080203.
FT DOMAIN 30 88 Chromo 1.
FT DOMAIN 121 179 Chromo 2; shadow subtype.
FT MOD_RES 10 10 N6-acetyllysine.
FT MOD_RES 44 44 N6-acetyllysine.
FT MOD_RES 50 50 N6-acetyllysine.
FT MOD_RES 93 93 Phosphoserine.
FT MOD_RES 95 95 Phosphoserine.
FT MOD_RES 97 97 Phosphoserine.
FT MOD_RES 99 99 Phosphoserine.
FT MOD_RES 176 176 Phosphoserine.
FT CONFLICT 111 111 A -> G (in Ref. 5; AAH14380).
FT CONFLICT 111 111 A -> V (in Ref. 4; AAF62370).
FT CONFLICT 130 130 T -> I (in Ref. 1; AAB48101 and 3;
FT BAA83340).
FT STRAND 29 41
FT STRAND 44 51
FT HELIX 56 58
FT STRAND 60 63
FT HELIX 64 66
FT HELIX 70 80
FT HELIX 116 119
FT STRAND 123 130
FT STRAND 137 142
FT STRAND 149 152
FT HELIX 153 159
FT HELIX 161 171
SQ SEQUENCE 183 AA; 20811 MW; 5928C63E0C93A76A CRC64;
MASNKTTLQK MGKKQNGKSK KVEEAEPEEF VVEKVLDRRV VNGKVEYFLK WKGFTDADNT
WEPEENLDCP ELIEAFLNSQ KAGKEKDGTK RKSLSDSESD DSKSKKKRDA ADKPRGFARG
LDPERIIGAT DSSGELMFLM KWKDSDEADL VLAKEANMKC PQIVIAFYEE RLTWHSCPED
EAQ
//
MIM
604477
*RECORD*
*FIELD* NO
604477
*FIELD* TI
*604477 CHROMOBOX HOMOLOG 3; CBX3
;;HP1, DROSOPHILA, HOMOLOG OF, GAMMA;;
HP1-GAMMA
read more*FIELD* TX
CLONING
At the nuclear envelope in higher eukaryotic cells, the nuclear lamina
and the heterochromatin are adjacent to the inner nuclear membrane.
Using the nucleoplasmic N terminus of lamin B receptor (LBR; 600024), an
integral protein of the inner nuclear membrane, as bait in a yeast
2-hybrid screen of a HeLa cell cDNA library, Ye and Worman (1996) showed
that LBR binds to 2 chromodomain proteins that are homologs of
Drosophila HP1. One of these proteins, CBX3, contains 173 amino acids
and shows 65% sequence similarity with the other protein, CBX5 (604478).
GENE FUNCTION
Ye and Worman (1996) found that LBR fusion proteins bound to CBX
proteins synthesized by in vitro translation and present in cell
lysates. LBR also coimmunoprecipitated the CBX proteins from cell
extracts. Ye and Worman (1996) suggested that the interaction between
LBR and the chromodomain proteins may explain, in part, the association
of heterochromatin with the inner nuclear membrane.
Following overexpression of MIS12 (609178) in HeLa cells, Obuse et al.
(2004) immunoprecipitated several proteins, including HP1-gamma, that
interacted with MIS12 in a kinetochore-associated complex. Both
HP1-alpha (CBX5) and HP1-gamma interacted directly with MIS12 and
C20ORF172 (609175). Using HP1 RNA interference (RNAi), Obuse et al.
(2004) found that HP1-alpha and HP1-gamma were functionally redundant.
In double HP1 RNAi, the integrity of kinetochores was abolished and
micronuclei were formed. Obuse et al. (2004) hypothesized that the firm
association of heterochromatic HP1 with the MIS12 complex may be a
fundamental feature of human kinetochore formation.
Fischle et al. (2005) demonstrated that HP1-alpha (604478), HP1-beta
(604511), and HP1-gamma are released from chromatin during the M phase
of the cell cycle even though trimethylation levels of histone H3 (see
602810) lys9 remain unchanged. However, the additional transient
modification of histone H3 by phosphorylation of ser10 next to the more
stable methyl-lys9 mark is sufficient to eject HP1 proteins from their
binding sites. Inhibition or depletion of the mitotic kinase Aurora B
(604970), which phosphorylates histone H3 on ser10, causes retention of
HP1 proteins on mitotic chromosomes, suggesting that H3 ser10
phosphorylation is necessary for the dissociation of HP1 from chromatin
in M phase. Fischle et al. (2005) concluded that their findings
establish a regulatory mechanism of protein-protein interactions,
through a combinatorial readout of 2 adjacent posttranslational
modifications: a stable methylation and a dynamic phosphorylation mark.
Smallwood et al. (2007) demonstrated that DNMT1 (126375) could interact
with HP1-alpha, HP1-beta, and HP1-gamma in a human colon carcinoma cell
line, resulting in stimulation of DNMT1 methyltransferase activity. The
HP1 proteins were sufficient to target DNMT1 activity in vivo, and
HP1-dependent repression required DNMT1. Smallwood et al. (2007)
demonstrated that HP1-alpha and HP1-beta were recruited to the survivin
(BIRC5; 603352) promoter in a DNMT1-dependent manner, whereas HP1-gamma
was present when the survivin gene was active. They concluded that
direct interactions between HP1 proteins and DNMT1 mediate silencing of
euchromatic genes.
MAPPING
The International Radiation Mapping Consortium mapped the CBX3 gene to
chromosome 7 (TMAP SHGC-57830).
*FIELD* RF
1. Fischle, W.; Tseng, B. S.; Dormann, H. L.; Ueberheide, B. M.; Garcia,
B. A.; Shabanowitz, J.; Hunt, D. F.; Funabiki, H.; Allis, C. D.:
Regulation of HP1-chromatin binding by histone H3 methylation and
phosphorylation. Nature 438: 1116-1122, 2005.
2. Obuse, C.; Iwasaki, O.; Kiyomitsu, T.; Goshima, G.; Toyoda, Y.;
Yanagida, M.: A conserved Mis12 centromere complex is linked to heterochromatic
HP1 and outer kinetochore protein Zwint-1. Nature Cell Biol. 6:
1135-1141, 2004.
3. Smallwood, A.; Esteve, P.-O.; Pradhan, S.; Carey, M.: Functional
cooperation between HP1 and DNMT1 mediates gene silencing. Genes
Dev. 21: 1169-1178, 2007.
4. Ye, Q.; Worman, H. J.: Interaction between an integral protein
of the nuclear envelope inner membrane and human chromodomain proteins
homologous to Drosophila HP1. J. Biol. Chem. 271: 14653-14656, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 7/10/2007
Ada Hamosh - updated: 1/12/2006
Patricia A. Hartz - updated: 1/28/2005
*FIELD* CD
Paul J. Converse: 1/30/2000
*FIELD* ED
mgross: 02/05/2013
mgross: 7/10/2007
alopez: 1/13/2006
terry: 1/12/2006
carol: 9/13/2005
mgross: 1/28/2005
alopez: 8/9/2000
carol: 1/31/2000
*RECORD*
*FIELD* NO
604477
*FIELD* TI
*604477 CHROMOBOX HOMOLOG 3; CBX3
;;HP1, DROSOPHILA, HOMOLOG OF, GAMMA;;
HP1-GAMMA
read more*FIELD* TX
CLONING
At the nuclear envelope in higher eukaryotic cells, the nuclear lamina
and the heterochromatin are adjacent to the inner nuclear membrane.
Using the nucleoplasmic N terminus of lamin B receptor (LBR; 600024), an
integral protein of the inner nuclear membrane, as bait in a yeast
2-hybrid screen of a HeLa cell cDNA library, Ye and Worman (1996) showed
that LBR binds to 2 chromodomain proteins that are homologs of
Drosophila HP1. One of these proteins, CBX3, contains 173 amino acids
and shows 65% sequence similarity with the other protein, CBX5 (604478).
GENE FUNCTION
Ye and Worman (1996) found that LBR fusion proteins bound to CBX
proteins synthesized by in vitro translation and present in cell
lysates. LBR also coimmunoprecipitated the CBX proteins from cell
extracts. Ye and Worman (1996) suggested that the interaction between
LBR and the chromodomain proteins may explain, in part, the association
of heterochromatin with the inner nuclear membrane.
Following overexpression of MIS12 (609178) in HeLa cells, Obuse et al.
(2004) immunoprecipitated several proteins, including HP1-gamma, that
interacted with MIS12 in a kinetochore-associated complex. Both
HP1-alpha (CBX5) and HP1-gamma interacted directly with MIS12 and
C20ORF172 (609175). Using HP1 RNA interference (RNAi), Obuse et al.
(2004) found that HP1-alpha and HP1-gamma were functionally redundant.
In double HP1 RNAi, the integrity of kinetochores was abolished and
micronuclei were formed. Obuse et al. (2004) hypothesized that the firm
association of heterochromatic HP1 with the MIS12 complex may be a
fundamental feature of human kinetochore formation.
Fischle et al. (2005) demonstrated that HP1-alpha (604478), HP1-beta
(604511), and HP1-gamma are released from chromatin during the M phase
of the cell cycle even though trimethylation levels of histone H3 (see
602810) lys9 remain unchanged. However, the additional transient
modification of histone H3 by phosphorylation of ser10 next to the more
stable methyl-lys9 mark is sufficient to eject HP1 proteins from their
binding sites. Inhibition or depletion of the mitotic kinase Aurora B
(604970), which phosphorylates histone H3 on ser10, causes retention of
HP1 proteins on mitotic chromosomes, suggesting that H3 ser10
phosphorylation is necessary for the dissociation of HP1 from chromatin
in M phase. Fischle et al. (2005) concluded that their findings
establish a regulatory mechanism of protein-protein interactions,
through a combinatorial readout of 2 adjacent posttranslational
modifications: a stable methylation and a dynamic phosphorylation mark.
Smallwood et al. (2007) demonstrated that DNMT1 (126375) could interact
with HP1-alpha, HP1-beta, and HP1-gamma in a human colon carcinoma cell
line, resulting in stimulation of DNMT1 methyltransferase activity. The
HP1 proteins were sufficient to target DNMT1 activity in vivo, and
HP1-dependent repression required DNMT1. Smallwood et al. (2007)
demonstrated that HP1-alpha and HP1-beta were recruited to the survivin
(BIRC5; 603352) promoter in a DNMT1-dependent manner, whereas HP1-gamma
was present when the survivin gene was active. They concluded that
direct interactions between HP1 proteins and DNMT1 mediate silencing of
euchromatic genes.
MAPPING
The International Radiation Mapping Consortium mapped the CBX3 gene to
chromosome 7 (TMAP SHGC-57830).
*FIELD* RF
1. Fischle, W.; Tseng, B. S.; Dormann, H. L.; Ueberheide, B. M.; Garcia,
B. A.; Shabanowitz, J.; Hunt, D. F.; Funabiki, H.; Allis, C. D.:
Regulation of HP1-chromatin binding by histone H3 methylation and
phosphorylation. Nature 438: 1116-1122, 2005.
2. Obuse, C.; Iwasaki, O.; Kiyomitsu, T.; Goshima, G.; Toyoda, Y.;
Yanagida, M.: A conserved Mis12 centromere complex is linked to heterochromatic
HP1 and outer kinetochore protein Zwint-1. Nature Cell Biol. 6:
1135-1141, 2004.
3. Smallwood, A.; Esteve, P.-O.; Pradhan, S.; Carey, M.: Functional
cooperation between HP1 and DNMT1 mediates gene silencing. Genes
Dev. 21: 1169-1178, 2007.
4. Ye, Q.; Worman, H. J.: Interaction between an integral protein
of the nuclear envelope inner membrane and human chromodomain proteins
homologous to Drosophila HP1. J. Biol. Chem. 271: 14653-14656, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 7/10/2007
Ada Hamosh - updated: 1/12/2006
Patricia A. Hartz - updated: 1/28/2005
*FIELD* CD
Paul J. Converse: 1/30/2000
*FIELD* ED
mgross: 02/05/2013
mgross: 7/10/2007
alopez: 1/13/2006
terry: 1/12/2006
carol: 9/13/2005
mgross: 1/28/2005
alopez: 8/9/2000
carol: 1/31/2000