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Symbol CBX5 contributors: mct - updated : 01-06-2018
HGNC name chromobox homolog 5
HGNC id 1555
  • a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues
  • a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins
    interspecies homolog to murine Cbx5 (97.9pc)
    homolog to Drosophila hp1b
    homolog to C.elegans K01G5.2A
    homolog to rattus Cbx5 (97.9pc)
    intraspecies homolog to CBX3
  • polycomb group proteins family
  • heterochromatin protein family
  • CATEGORY regulatory , structural protein , antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nuclear envelope
  • localizes to heterochromatin in interphase cells but is liberated from chromosomal arms at the onset of mitosis
  • basic FUNCTION
  • may interact with lamin B receptor (LBR) to contribute to the association of the heterochromatin with the inner nuclear membrane
  • mediating gene silencing
  • is released from chromatin during the M phase of the cell cycle, upon H3 serine 10 phosphorylation
  • chromatin-associated protein, effector of SUMO-dependent changes in chromatin structure and gene expression
  • is involved in the formation of functional kinetochore through interaction with essential kinetochore proteins
  • recruited to the BIRC5 promoter in a DNMT1-dependent manner, thus mediating silencing of euchromatic genes
  • involved in transient repression of inducible promoters
  • essential role in heterochromatin formation and mitotic progression through its interaction with various proteins
  • heterochromatin-associated protein localizing to pericentromeres and telomeres, which has a dose-dependent effect on gene silencing, and a critical role in heterochromatin formation and maintenance
  • with ORC3 and ORC2, may be recruited to the chromatin as a single complex and require each other for their stable association to heterochromatin
  • with ORC2, are required for condensation of centric heterochromatic satellite repeats
  • novel role during the cellular response to oxidative stress
  • potentially acts as a rapid redox sensor, and it may connect the intracellular redox state with transcriptional regulation under various physiological conditions
  • in homology-directed repair (HDR) is linked to the DNA-end resection step of DNA breaks, through the promotion of RPA loading and phosphorylation at damage site
  • promotes nucleosome associations that drive chromatin condensation
  • phosphorylation-dephosphorylation cycle of CBX5 orchestrates accurate progression of cells through mitosis
  • chromosomal protein that binds lysine 9-methylated histone H3 (H3K9me), a hallmark of heterochromatin, and plays a crucial role in forming higher-order chromatin structures
  • is involved in regulation of chromatin plasticity, DNA damage repair, and centromere dynamics
  • essential link between CBX5-interacting molecular dynamics and chromosome plasticity in promoting accurate cell division
  • evolutionary conserved protein that binds histone H3 di- or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures
  • involved in the epigenetic regulation of gene silencing
  • plays an important role in the differentiation and angiogenic function of endothelial stem/progenitor cells (EPCs) by regulating endothelial gene expression
  • CBX5-oligomerization is critical to the maintenance of heterochromatin and the tunable dynamics of this HP1 isoform
  • WDR76 co-localizes to puncta with the heterochromatin proteins CBX1 and CBX5, which are also recruited to DNA damage but much less intensely than WDR76
  • is a gene that mediates chromatin conformation, gene silencing and cancer progression
  • specific role for CBX1, CBX3, CBX5 in regulating SUV39H1 function under stress via a feedback mechanism that likely regulates heterochromatin formation
  • forms and maintains the domains of heterochromatin through the interaction of its chromodomain with trimethylated lysine 9 of histone 3, although this interaction is not the sole determinant
  • CELLULAR PROCESS nucleotide, chromatin organization, remodeling
    nucleotide, transcription, regulation
    a component
  • component of the heterochromatin
  • associating with CHAF1B-CBX5 chaperone complex and monomethylating K9 on non nucleosomal histone H3, thus providing H3K9me1 for subsequent trimethylation by SUV39H1/H2 in pericentric regions
  • conserved components of eukaryotic constitutive heterochromatin
  • TRIM28 is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (CBX5)
    DNA binding
    small molecule
  • binding to methyl-lysine of proteins like histone H3
  • binding to nucleoplasmic domain of inner nuclear membrane receptor lamin B
  • binding to CHAF1A
  • interacting with HNRNPU
  • bind to POGZ through zinc-finger-like motif (interaction of POGZ with CBX5 may regulate Aurora B activation and a variety of downstream mitotic events)
  • mitotic function of NSL1 and CBX5 requires their functional association at interphase
  • SENP7 interacts directly with CBX5, localizes at CBX5-enriched pericentric domains and can deconjugate SUMOylated CBX5
  • interaction with SENP7 (SENP7L decreases epithelial gene expression via an unidentified CBX5-independent pathway, and concurrently with the CBX5-dependent pathway promotes dedifferentiation of cancer cells)
  • KLF11 recruits CBX5 and its histone methyltransferase, SUV39H1, to promoters to limit KLF11-mediated gene activation
  • UBE2A physically interacts with CBX5 and ubiquitinates CBX5 at residue K154, thereby promoting CBX5 degradation through the autophagy pathway and eventually leading to an open chromatin structure that facilitates efficient HR DSB repair
  • downregulation of CBX5 can decrease H3K9me3 enrichment and DNA methylation rate of SFRP1 promoter, resulting in restoring the expression of SFRP1
  • DMRT2 can lead to the enrichment of CBX5 at telomeres to maintain heterochromatin
  • cell & other
    Other YY1 positively regulates CBX5 expression
    phosphorylated, acetylated, methylated, formylated
    SUMOylation promotes targeting of CBX5 to pericentric heterochromatin
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    reduced in invasive breast cancer cell lines, suggesting that reduced CBX5 expression may lead to impaired epigenetic silencing of genes that are important in the acquisition of an invasive phenotype
    tumoral     --over  
    and H3K9me3 in glioma cells are functionally associated with glioma pathogenesis and progression
    Variant & Polymorphism
    Candidate gene
    Therapy target