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{{Infobox_gene}}
{{PBB_Controls
'''Chromobox protein homolog 5''' is a [[protein]] that in humans is encoded by the ''CBX5'' [[gene]].<ref name="pmid8663349">{{cite journal | vauthors = Ye Q, Worman HJ | title = Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 25 | pages = 14653–6 | date = Jun 1996 | pmid = 8663349 | pmc =  | doi = 10.1074/jbc.271.25.14653 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CBX5 chromobox homolog 5 (HP1 alpha homolog, Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23468| accessdate = }}</ref> It is a highly conserved, non-histone protein part of the [[Heterochromatin protein 1|heterochromatin family]]. The protein itself is more commonly called (in humans) HP1α.{{citation needed|date=January 2016}} Heterochromatin protein-1 (HP1) has an N-terminal domain that acts on methylated lysines residues leading to epigenetic repression.<ref name=":2" /> The C-terminal of this protein has a chromo shadow-domain (CSD) that is responsible for [[Homodimerize|homodimerizing]], as well as interacting with a variety of chromatin-associated, non-histone proteins.<ref name=":0" />
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== Structure ==
{{GNF_Protein_box
HP1α is 191 amino acids in length containing 6 exons.<ref name=":2">{{Cite web|title = OMIM Entry- * 604478 - CHROMOBOX HOMOLOG 5; CBX5|url = http://omim.org/entry/604478#2|website = omim.org|accessdate = 2015-11-02}}</ref><ref name=":0">{{cite journal | vauthors = Lomberk G, Wallrath L, Urrutia R | year = 2006 | title = The heterochromatin protein 1 family | journal = Genome Biol | volume = 7 | issue = 7| page = 228 | doi=10.1186/gb-2006-7-7-228 | pmid=17224041 | pmc=1779566}}</ref> As mentioned above, this protein contains two domains, an N-terminal chromodomain (CD) and a C- terminal chromoshadow domain (CSD). The CD binds with histone 3 through a methylated lysine residue at position 9 (H3K9) while the C-terminal CSD homodimerizes and interacts with a variety of other chromatin-associated, non-histone related proteins.<ref name=":0" /> Connecting these two domains is the hinge region.<ref name=":1">{{Cite journal|title = Heterochromatin Protein 1: a pervasive controlling influence|last = Hiragami|first = K|date = 15 August 2005|journal = Cellular and Molecular Life Sciences|doi = 10.1007/s00018-005-5287-9|pmid = 16261261|volume=62|issue = 23|pages=2711–2726}}</ref>
| image =
| image_source =
| PDB =  
| Name = Chromobox homolog 5 (HP1 alpha homolog, Drosophila)
| HGNCid = 1555
| Symbol = CBX5
| AltSymbols =; HP1; HP1-ALPHA; HP1Hs-alpha
| OMIM = 604478
| ECnumber = 
| Homologene = 7257
| MGIid = 109372
| GeneAtlas_image1 = PBB_GE_CBX5_209715_at_tn.png
| Function = {{GNF_GO|id=GO:0003682 |text = chromatin binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0000776 |text = kinetochore}} {{GNF_GO|id=GO:0000785 |text = chromatin}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005635 |text = nuclear envelope}} {{GNF_GO|id=GO:0005720 |text = nuclear heterochromatin}}
| Process = {{GNF_GO|id=GO:0006333 |text = chromatin assembly or disassembly}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 23468
    | Hs_Ensembl = ENSG00000094916
    | Hs_RefseqProtein = NP_036249
    | Hs_RefseqmRNA = NM_012117
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 52921003
    | Hs_GenLoc_end = 52960153
    | Hs_Uniprot = P45973
    | Mm_EntrezGene = 12419
    | Mm_Ensembl = ENSMUSG00000009575
    | Mm_RefseqmRNA = XM_001000807
    | Mm_RefseqProtein = XP_001000807
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 15
    | Mm_GenLoc_start = 103024721
    | Mm_GenLoc_end = 103067850
    | Mm_Uniprot = Q61686
  }}
}}
'''Chromobox homolog 5 (HP1 alpha homolog, Drosophila)''', also known as '''CBX5''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CBX5 chromobox homolog 5 (HP1 alpha homolog, Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23468| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
=== Chromodomain ===
{{PBB_Summary
Once translated, the chromodomain will take on a globular conformation consisting of three β-sheets and one α-helix. The β-sheets are packed up against the helix at the carboxy terminal segment.<ref name=":1" /> The charges on the β sheets are negative thus making it difficult for it to bind to the DNA as a DNA-binding motif. Instead, HP1α binds to the histones as a protein interaction motif.<ref name=":0" /> Specific binding to CD to the methylated H3K9 is mediated by three hydrophobic side chains called the "hydrophobic box". Other sites on HP1 will interact with the H3 tails from neighbouring histones which will give structure to the flexible N-terminal tail of the histones. Neighbouring H3 histones can affect HP1 binding by post-translationally modifying the tails.<ref name=":1" />
| section_title =
| summary_text = Heterochromatin protein-1 (HP1) is a methyl-lysine binding protein localized at heterochromatin sites, where it mediates gene silencing.[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: CBX5 chromobox homolog 5 (HP1 alpha homolog, Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23468| accessdate = }}</ref>
}}


==See also==
=== Chromoshadow domain ===
The CSD much resembles that of the CD. It too has a globular conformation containing three β-sheets, however it possesses two α-helices as opposed to just the one in the CD.<ref name=":1" /> The CSD readily homodimerizes ''in vitro'' and as a result forms a groove which can accommodate HP1 associated proteins that have a specific consensus sequence: PxVxL, where P is Proline, V is Valine, L is Leucine and x is any amino acid.<ref name=":0" />
 
== Mechanism of action ==
HP1α primarily functions as a gene silencer, which is dependent on the interactions between the CD and the methyl H3K9 mark.<ref>{{Cite web|title = CBX5 chromobox homolog 5 [Homo sapiens (human)] - Gene - NCBI|url = https://www.ncbi.nlm.nih.gov/gene/23468|website = www.ncbi.nlm.nih.gov|accessdate = 2015-10-16}}</ref> The hydrophobic box on the CD provides the appropriate environment for the methylated lysine residue. While the exact mechanism of how gene silencing is done is unknown, experimental data concluded the rapid exchange of biological macromolecules in and out of the heterochromatin region. This suggests HP1 isn't acting as a glue holding the heterochromatin together, but rather there are competing molecules within that interact in various ways to create a closed complex leading to gene repression or an open, euchromatin structure with gene activation. HP1 concentration is higher and more static in areas of the chromosome where methylated H3K9 residues reside, giving the chromosome its closed, gene-repressed heterochromatin structure.<ref name=":1" /> It has also been shown that the more methylated the H3 lysine is, the higher the affinity HP1 has for it. That is, trimethylated lysine residues bind tighter to HP1 than dimethylated residues, which bind better than monomethylated residues.
 
The localisation driving factor is currently unknown.<ref name=":1" />
 
== Evolutionary conservation ==
HP1α is a highly evolutionary conserved protein, existing in species such a ''Schizosaccharomyces pombe'', a type of yeast, all the way to humans.<ref name=":1" /> The N-terminal chromodomain and C-terminal chromoshadow domain appear to be much more conserved (approximately 50-70% amino acid similarity) than the hinge region (approximately 25-30% similarity with the ''Drosophila'' HP1 homolog).<ref name=":1" />
 
== Interactions  ==
 
CBX5 (gene) has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[CBX1]],<ref name = pmid11336697/>
* [[CBX3]],<ref name = pmid11336697/>
* [[CHAF1A]],<ref name = pmid12697822/><ref name = pmid10938122/>
* [[DNMT3B]],<ref name = pmid12867029>{{cite journal | vauthors = Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH | title = Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin | journal = Current Biology | volume = 13 | issue = 14 | pages = 1192–200 | date = Jul 2003 | pmid = 12867029 | doi =  10.1016/s0960-9822(03)00432-9}}</ref>
* [[HDAC4]],<ref name = pmid12242305/>
* [[HDAC9]],<ref name = pmid12242305>{{cite journal | vauthors = Zhang CL, McKinsey TA, Olson EN | title = Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation | journal = Molecular and Cellular Biology | volume = 22 | issue = 20 | pages = 7302–12 | date = Oct 2002 | pmid = 12242305 | pmc = 139799 | doi =  10.1128/mcb.22.20.7302-7312.2002}}</ref>
* [[Histone deacetylase 5]],<ref name = pmid12242305/>
* [[Ku70]],<ref name = pmid11112778>{{cite journal | vauthors = Song K, Jung Y, Jung D, Lee I | title = Human Ku70 interacts with heterochromatin protein 1alpha | journal = The Journal of Biological Chemistry | volume = 276 | issue = 11 | pages = 8321–7 | date = Mar 2001 | pmid = 11112778 | doi = 10.1074/jbc.M008779200 }}</ref>
* [[Lamin B receptor]],<ref name = autogenerated1>{{cite journal | vauthors = Ye Q, Worman HJ | title = Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 25 | pages = 14653–6 | date = Jun 1996 | pmid = 8663349 | doi =  10.1074/jbc.271.25.14653}}</ref>
* [[MBD1]],<ref name = pmid12697822>{{cite journal | vauthors = Reese BE, Bachman KE, Baylin SB, Rountree MR | title = The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1 | journal = Molecular and Cellular Biology | volume = 23 | issue = 9 | pages = 3226–36 | date = May 2003 | pmid = 12697822 | pmc = 153189 | doi =  10.1128/mcb.23.9.3226-3236.2003}}</ref><ref name = pmid12711603>{{cite journal | vauthors = Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M | title = Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression | journal = The Journal of Biological Chemistry | volume = 278 | issue = 26 | pages = 24132–8 | date = Jun 2003 | pmid = 12711603 | doi = 10.1074/jbc.M302283200 }}</ref>
* [[MIS12]],<ref name = pmid15502821>{{cite journal | vauthors = Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M | title = A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1 | journal = Nature Cell Biology | volume = 6 | issue = 11 | pages = 1135–41 | date = Nov 2004 | pmid = 15502821 | doi = 10.1038/ncb1187 }}</ref>
* [[SMARCA4]],<ref name = pmid12411497/>
* [[SUV39H1]],<ref name = pmid12242305/><ref name = pmid12711603/><ref name = pmid16189514>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = Oct 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}</ref>
* [[TAF4]],<ref name = pmid11959914>{{cite journal | vauthors = Vassallo MF, Tanese N | title = Isoform-specific interaction of HP1 with human TAFII130 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 9 | pages = 5919–24 | date = Apr 2002 | pmid = 11959914 | pmc = 122877 | doi = 10.1073/pnas.092025499 }}</ref>  and
* [[TRIM28]].<ref name = pmid11336697>{{cite journal | vauthors = Nielsen AL, Oulad-Abdelghani M, Ortiz JA, Remboutsika E, Chambon P, Losson R | title = Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins | journal = Molecular Cell | volume = 7 | issue = 4 | pages = 729–39 | date = Apr 2001 | pmid = 11336697 | doi =  10.1016/S1097-2765(01)00218-0}}</ref><ref name = pmid10938122>{{cite journal | vauthors = Lechner MS, Begg GE, Speicher DW, Rauscher FJ | title = Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential | journal = Molecular and Cellular Biology | volume = 20 | issue = 17 | pages = 6449–65 | date = Sep 2000 | pmid = 10938122 | pmc = 86120 | doi =  10.1128/mcb.20.17.6449-6465.2000}}</ref><ref name = pmid12411497>{{cite journal | vauthors = Nielsen AL, Sanchez C, Ichinose H, Cerviño M, Lerouge T, Chambon P, Losson R | title = Selective interaction between the chromatin-remodeling factor BRG1 and the heterochromatin-associated protein HP1alpha | journal = The EMBO Journal | volume = 21 | issue = 21 | pages = 5797–806 | date = Nov 2002 | pmid = 12411497 | pmc = 131057 | doi =  10.1093/emboj/cdf560}}</ref><ref name = pmid12154074>{{cite journal | vauthors = Cammas F, Oulad-Abdelghani M, Vonesch JL, Huss-Garcia Y, Chambon P, Losson R | title = Cell differentiation induces TIF1beta association with centromeric heterochromatin via an HP1 interaction | journal = Journal of Cell Science | volume = 115 | issue = Pt 17 | pages = 3439–48 | date = Sep 2002 | pmid = 12154074 | doi =  }}</ref>
* [[STAT5A]],<ref name = pmid23733954>{{cite journal | vauthors = Hu X, Dutta P, Tsurumi A, Li J, Wang J, Land H, Li WX | title = Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth | journal = Proc Natl Acad Sci U S A | volume = 110  | issue = 25 | pages = 10213–10218 | date = Jun 2013 | pmid = 23733954 | doi = 10.1073/pnas.1221243110 | pmc=3690839}}</ref>
{{Div col end}}
 
== See also ==
* [[Heterochromatin protein 1]]
* [[Heterochromatin protein 1]]


==References==
== References ==
{{reflist|2}}
{{reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Saunders WS, Chue C, Goebl M, Craig C, Clark RF, Powers JA, Eissenberg JC, Elgin SC, Rothfield NF, Earnshaw WC | title = Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity | journal = Journal of Cell Science | volume = 104 | issue = 2 | pages = 573–82 | date = Feb 1993 | pmid = 8505380 | doi =  }}
| citations =
* {{cite journal | vauthors = Sugimoto K, Yamada T, Muro Y, Himeno M | title = Human homolog of Drosophila heterochromatin-associated protein 1 (HP1) is a DNA-binding protein which possesses a DNA-binding motif with weak similarity to that of human centromere protein C (CENP-C) | journal = Journal of Biochemistry | volume = 120 | issue = 1 | pages = 153–9 | date = Jul 1996 | pmid = 8864858 | doi = 10.1093/oxfordjournals.jbchem.a021378 }}
*{{cite journal | author=Saunders WS, Chue C, Goebl M, ''et al.'' |title=Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. |journal=J. Cell. Sci. |volume=104 ( Pt 2) |issue= |pages= 573-82 |year= 1993 |pmid= 8505380 |doi=  }}
* {{cite journal | vauthors = Ye Q, Callebaut I, Pezhman A, Courvalin JC, Worman HJ | title = Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR | journal = The Journal of Biological Chemistry | volume = 272 | issue = 23 | pages = 14983–9 | date = Jun 1997 | pmid = 9169472 | doi = 10.1074/jbc.272.23.14983 }}
*{{cite journal | author=Ye Q, Worman HJ |title=Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1. |journal=J. Biol. Chem. |volume=271 |issue= 25 |pages= 14653-6 |year= 1996 |pmid= 8663349 |doi= }}
* {{cite journal | vauthors = Lessard J, Baban S, Sauvageau G | title = Stage-specific expression of polycomb group genes in human bone marrow cells | journal = Blood | volume = 91 | issue = 4 | pages = 1216–24 | date = Feb 1998 | pmid = 9454751 | doi =  }}
*{{cite journal | author=Sugimoto K, Yamada T, Muro Y, Himeno M |title=Human homolog of Drosophila heterochromatin-associated protein 1 (HP1) is a DNA-binding protein which possesses a DNA-binding motif with weak similarity to that of human centromere protein C (CENP-C). |journal=J. Biochem. |volume=120 |issue= 1 |pages= 153-9 |year= 1997 |pmid= 8864858 |doi= }}
* {{cite journal | vauthors = Ainsztein AM, Kandels-Lewis SE, Mackay AM, Earnshaw WC | title = INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1 | journal = The Journal of Cell Biology | volume = 143 | issue = 7 | pages = 1763–74 | date = Dec 1998 | pmid = 9864353 | pmc = 2175214 | doi = 10.1083/jcb.143.7.1763 }}
*{{cite journal | author=Ye Q, Callebaut I, Pezhman A, ''et al.'' |title=Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. |journal=J. Biol. Chem. |volume=272 |issue= 23 |pages= 14983-9 |year= 1997 |pmid= 9169472 |doi=  }}
* {{cite journal | vauthors = Minc E, Allory Y, Worman HJ, Courvalin JC, Buendia B | title = Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells | journal = Chromosoma | volume = 108 | issue = 4 | pages = 220–34 | date = Aug 1999 | pmid = 10460410 | doi = 10.1007/s004120050372 }}
*{{cite journal | author=Lessard J, Baban S, Sauvageau G |title=Stage-specific expression of polycomb group genes in human bone marrow cells. |journal=Blood |volume=91 |issue= 4 |pages= 1216-24 |year= 1998 |pmid= 9454751 |doi= }}
* {{cite journal | vauthors = Murzina N, Verreault A, Laue E, Stillman B | title = Heterochromatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins | journal = Molecular Cell | volume = 4 | issue = 4 | pages = 529–40 | date = Oct 1999 | pmid = 10549285 | doi = 10.1016/S1097-2765(00)80204-X }}
*{{cite journal | author=Ainsztein AM, Kandels-Lewis SE, Mackay AM, Earnshaw WC |title=INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. |journal=J. Cell Biol. |volume=143 |issue= 7 |pages= 1763-74 |year= 1999 |pmid= 9864353 |doi= }}
* {{cite journal | vauthors = Nielsen AL, Ortiz JA, You J, Oulad-Abdelghani M, Khechumian R, Gansmuller A, Chambon P, Losson R | title = Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family | journal = The EMBO Journal | volume = 18 | issue = 22 | pages = 6385–95 | date = Nov 1999 | pmid = 10562550 | pmc = 1171701 | doi = 10.1093/emboj/18.22.6385 }}
*{{cite journal | author=Minc E, Allory Y, Worman HJ, ''et al.'' |title=Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells. |journal=Chromosoma |volume=108 |issue= 4 |pages= 220-34 |year= 1999 |pmid= 10460410 |doi= }}
* {{cite journal | vauthors = Zhao T, Heyduk T, Allis CD, Eissenberg JC | title = Heterochromatin protein 1 binds to nucleosomes and DNA in vitro | journal = The Journal of Biological Chemistry | volume = 275 | issue = 36 | pages = 28332–8 | date = Sep 2000 | pmid = 10882726 | doi = 10.1074/jbc.M003493200 }}
*{{cite journal | author=Murzina N, Verreault A, Laue E, Stillman B |title=Heterochromatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins. |journal=Mol. Cell |volume=4 |issue= 4 |pages= 529-40 |year= 1999 |pmid= 10549285 |doi= }}
* {{cite journal | vauthors = Lechner MS, Begg GE, Speicher DW, Rauscher FJ | title = Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential | journal = Molecular and Cellular Biology | volume = 20 | issue = 17 | pages = 6449–65 | date = Sep 2000 | pmid = 10938122 | pmc = 86120 | doi = 10.1128/MCB.20.17.6449-6465.2000 }}
*{{cite journal | author=Nielsen AL, Ortiz JA, You J, ''et al.'' |title=Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. |journal=EMBO J. |volume=18 |issue= 22 |pages= 6385-95 |year= 2000 |pmid= 10562550 |doi= 10.1093/emboj/18.22.6385 }}
* {{cite journal | vauthors = Song K, Jung Y, Jung D, Lee I | title = Human Ku70 interacts with heterochromatin protein 1alpha | journal = The Journal of Biological Chemistry | volume = 276 | issue = 11 | pages = 8321–7 | date = Mar 2001 | pmid = 11112778 | doi = 10.1074/jbc.M008779200 }}
*{{cite journal | author=Zhao T, Heyduk T, Allis CD, Eissenberg JC |title=Heterochromatin protein 1 binds to nucleosomes and DNA in vitro. |journal=J. Biol. Chem. |volume=275 |issue= 36 |pages= 28332-8 |year= 2000 |pmid= 10882726 |doi= 10.1074/jbc.M003493200 }}
* {{cite journal | vauthors = Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T | title = Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins | journal = Nature | volume = 410 | issue = 6824 | pages = 116–20 | date = Mar 2001 | pmid = 11242053 | doi = 10.1038/35065132 }}
*{{cite journal | author=Lechner MS, Begg GE, Speicher DW, Rauscher FJ |title=Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential. |journal=Mol. Cell. Biol. |volume=20 |issue= 17 |pages= 6449-65 |year= 2000 |pmid= 10938122 |doi= }}
* {{cite journal | vauthors = Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T | title = Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain | journal = Nature | volume = 410 | issue = 6824 | pages = 120–4 | date = Mar 2001 | pmid = 11242054 | doi = 10.1038/35065138 }}
*{{cite journal | author=Song K, Jung Y, Jung D, Lee I |title=Human Ku70 interacts with heterochromatin protein 1alpha. |journal=J. Biol. Chem. |volume=276 |issue= 11 |pages= 8321-7 |year= 2001 |pmid= 11112778 |doi= 10.1074/jbc.M008779200 }}
* {{cite journal | vauthors = Nielsen AL, Oulad-Abdelghani M, Ortiz JA, Remboutsika E, Chambon P, Losson R | title = Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins | journal = Molecular Cell | volume = 7 | issue = 4 | pages = 729–39 | date = Apr 2001 | pmid = 11336697 | doi = 10.1016/S1097-2765(01)00218-0 }}
*{{cite journal | author=Lachner M, O'Carroll D, Rea S, ''et al.'' |title=Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. |journal=Nature |volume=410 |issue= 6824 |pages= 116-20 |year= 2001 |pmid= 11242053 |doi= 10.1038/35065132 }}
* {{cite journal | vauthors = Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC | title = INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis | journal = Current Biology | volume = 11 | issue = 11 | pages = 886–90 | date = Jun 2001 | pmid = 11516652 | doi = 10.1016/S0960-9822(01)00238-X }}
*{{cite journal | author=Bannister AJ, Zegerman P, Partridge JF, ''et al.'' |title=Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. |journal=Nature |volume=410 |issue= 6824 |pages= 120-4 |year= 2001 |pmid= 11242054 |doi= 10.1038/35065138 }}
* {{cite journal | vauthors = Scholzen T, Endl E, Wohlenberg C, van der Sar S, Cowell IG, Gerdes J, Singh PB | title = The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure | journal = The Journal of Pathology | volume = 196 | issue = 2 | pages = 135–44 | date = Feb 2002 | pmid = 11793364 | doi = 10.1002/path.1016 }}
*{{cite journal | author=Nielsen AL, Oulad-Abdelghani M, Ortiz JA, ''et al.'' |title=Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. |journal=Mol. Cell |volume=7 |issue= 4 |pages= 729-39 |year= 2001 |pmid= 11336697 |doi= }}
* {{cite journal | vauthors = Weinmann AS, Yan PS, Oberley MJ, Huang TH, Farnham PJ | title = Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis | journal = Genes & Development | volume = 16 | issue = 2 | pages = 235–44 | date = Jan 2002 | pmid = 11799066 | pmc = 155318 | doi = 10.1101/gad.943102 }}
*{{cite journal | author=Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC |title=INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. |journal=Curr. Biol. |volume=11 |issue= 11 |pages= 886-90 |year= 2001 |pmid= 11516652 |doi= }}
* {{cite journal | vauthors = Sugimoto K, Tasaka H, Dotsu M | title = Molecular behavior in living mitotic cells of human centromere heterochromatin protein HPLalpha ectopically expressed as a fusion to red fluorescent protein | journal = Cell Structure and Function | volume = 26 | issue = 6 | pages = 705–18 | date = Dec 2001 | pmid = 11942629 | doi = 10.1247/csf.26.705 }}
*{{cite journal | author=Scholzen T, Endl E, Wohlenberg C, ''et al.'' |title=The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure. |journal=J. Pathol. |volume=196 |issue= 2 |pages= 135-44 |year= 2002 |pmid= 11793364 |doi= 10.1002/path.1016 }}
* {{cite journal | vauthors = Vassallo MF, Tanese N | title = Isoform-specific interaction of HP1 with human TAFII130 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 9 | pages = 5919–24 | date = Apr 2002 | pmid = 11959914 | pmc = 122877 | doi = 10.1073/pnas.092025499 }}
*{{cite journal | author=Weinmann AS, Yan PS, Oberley MJ, ''et al.'' |title=Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. |journal=Genes Dev. |volume=16 |issue= 2 |pages= 235-44 |year= 2002 |pmid= 11799066 |doi= 10.1101/gad.943102 }}
*{{cite journal | author=Sugimoto K, Tasaka H, Dotsu M |title=Molecular behavior in living mitotic cells of human centromere heterochromatin protein HPLalpha ectopically expressed as a fusion to red fluorescent protein. |journal=Cell Struct. Funct. |volume=26 |issue= 6 |pages= 705-18 |year= 2002 |pmid= 11942629 |doi=  }}
*{{cite journal  | author=Vassallo MF, Tanese N |title=Isoform-specific interaction of HP1 with human TAFII130. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 9 |pages= 5919-24 |year= 2002 |pmid= 11959914 |doi= 10.1073/pnas.092025499 }}
}}
{{refend}}
{{refend}}
 
==External links==
== External links ==
* {{UCSC gene info|CBX5}}
* {{MeshName|CBX5+protein,+human}}
 
 
{{protein-stub}}
{{NLM content}}
{{Transcription factors}}
[[Category:Transcription factors]]
{{WikiDoc Sources}}

Latest revision as of 14:29, 11 January 2019

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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View/Edit Human

Chromobox protein homolog 5 is a protein that in humans is encoded by the CBX5 gene.[1][2] It is a highly conserved, non-histone protein part of the heterochromatin family. The protein itself is more commonly called (in humans) HP1α.[citation needed] Heterochromatin protein-1 (HP1) has an N-terminal domain that acts on methylated lysines residues leading to epigenetic repression.[3] The C-terminal of this protein has a chromo shadow-domain (CSD) that is responsible for homodimerizing, as well as interacting with a variety of chromatin-associated, non-histone proteins.[4]

Structure

HP1α is 191 amino acids in length containing 6 exons.[3][4] As mentioned above, this protein contains two domains, an N-terminal chromodomain (CD) and a C- terminal chromoshadow domain (CSD). The CD binds with histone 3 through a methylated lysine residue at position 9 (H3K9) while the C-terminal CSD homodimerizes and interacts with a variety of other chromatin-associated, non-histone related proteins.[4] Connecting these two domains is the hinge region.[5]

Chromodomain

Once translated, the chromodomain will take on a globular conformation consisting of three β-sheets and one α-helix. The β-sheets are packed up against the helix at the carboxy terminal segment.[5] The charges on the β sheets are negative thus making it difficult for it to bind to the DNA as a DNA-binding motif. Instead, HP1α binds to the histones as a protein interaction motif.[4] Specific binding to CD to the methylated H3K9 is mediated by three hydrophobic side chains called the "hydrophobic box". Other sites on HP1 will interact with the H3 tails from neighbouring histones which will give structure to the flexible N-terminal tail of the histones. Neighbouring H3 histones can affect HP1 binding by post-translationally modifying the tails.[5]

Chromoshadow domain

The CSD much resembles that of the CD. It too has a globular conformation containing three β-sheets, however it possesses two α-helices as opposed to just the one in the CD.[5] The CSD readily homodimerizes in vitro and as a result forms a groove which can accommodate HP1 associated proteins that have a specific consensus sequence: PxVxL, where P is Proline, V is Valine, L is Leucine and x is any amino acid.[4]

Mechanism of action

HP1α primarily functions as a gene silencer, which is dependent on the interactions between the CD and the methyl H3K9 mark.[6] The hydrophobic box on the CD provides the appropriate environment for the methylated lysine residue. While the exact mechanism of how gene silencing is done is unknown, experimental data concluded the rapid exchange of biological macromolecules in and out of the heterochromatin region. This suggests HP1 isn't acting as a glue holding the heterochromatin together, but rather there are competing molecules within that interact in various ways to create a closed complex leading to gene repression or an open, euchromatin structure with gene activation. HP1 concentration is higher and more static in areas of the chromosome where methylated H3K9 residues reside, giving the chromosome its closed, gene-repressed heterochromatin structure.[5] It has also been shown that the more methylated the H3 lysine is, the higher the affinity HP1 has for it. That is, trimethylated lysine residues bind tighter to HP1 than dimethylated residues, which bind better than monomethylated residues.

The localisation driving factor is currently unknown.[5]

Evolutionary conservation

HP1α is a highly evolutionary conserved protein, existing in species such a Schizosaccharomyces pombe, a type of yeast, all the way to humans.[5] The N-terminal chromodomain and C-terminal chromoshadow domain appear to be much more conserved (approximately 50-70% amino acid similarity) than the hinge region (approximately 25-30% similarity with the Drosophila HP1 homolog).[5]

Interactions

CBX5 (gene) has been shown to interact with:

See also

References

  1. ↑ Ye Q, Worman HJ (Jun 1996). "Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1". The Journal of Biological Chemistry. 271 (25): 14653–6. doi:10.1074/jbc.271.25.14653. PMID 8663349.
  2. ↑ "Entrez Gene: CBX5 chromobox homolog 5 (HP1 alpha homolog, Drosophila)".
  3. ↑ 3.0 3.1 "OMIM Entry- * 604478 - CHROMOBOX HOMOLOG 5; CBX5". omim.org. Retrieved 2015-11-02.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Lomberk G, Wallrath L, Urrutia R (2006). "The heterochromatin protein 1 family". Genome Biol. 7 (7): 228. doi:10.1186/gb-2006-7-7-228. PMC 1779566. PMID 17224041.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Hiragami, K (15 August 2005). "Heterochromatin Protein 1: a pervasive controlling influence". Cellular and Molecular Life Sciences. 62 (23): 2711–2726. doi:10.1007/s00018-005-5287-9. PMID 16261261.
  6. ↑ "CBX5 chromobox homolog 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2015-10-16.
  7. ↑ 7.0 7.1 7.2 Nielsen AL, Oulad-Abdelghani M, Ortiz JA, Remboutsika E, Chambon P, Losson R (Apr 2001). "Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins". Molecular Cell. 7 (4): 729–39. doi:10.1016/S1097-2765(01)00218-0. PMID 11336697.
  8. ↑ 8.0 8.1 Reese BE, Bachman KE, Baylin SB, Rountree MR (May 2003). "The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1". Molecular and Cellular Biology. 23 (9): 3226–36. doi:10.1128/mcb.23.9.3226-3236.2003. PMC 153189. PMID 12697822.
  9. ↑ 9.0 9.1 Lechner MS, Begg GE, Speicher DW, Rauscher FJ (Sep 2000). "Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential". Molecular and Cellular Biology. 20 (17): 6449–65. doi:10.1128/mcb.20.17.6449-6465.2000. PMC 86120. PMID 10938122.
  10. ↑ Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (Jul 2003). "Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin". Current Biology. 13 (14): 1192–200. doi:10.1016/s0960-9822(03)00432-9. PMID 12867029.
  11. ↑ 11.0 11.1 11.2 11.3 Zhang CL, McKinsey TA, Olson EN (Oct 2002). "Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation". Molecular and Cellular Biology. 22 (20): 7302–12. doi:10.1128/mcb.22.20.7302-7312.2002. PMC 139799. PMID 12242305.
  12. ↑ Song K, Jung Y, Jung D, Lee I (Mar 2001). "Human Ku70 interacts with heterochromatin protein 1alpha". The Journal of Biological Chemistry. 276 (11): 8321–7. doi:10.1074/jbc.M008779200. PMID 11112778.
  13. ↑ Ye Q, Worman HJ (Jun 1996). "Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1". The Journal of Biological Chemistry. 271 (25): 14653–6. doi:10.1074/jbc.271.25.14653. PMID 8663349.
  14. ↑ 14.0 14.1 Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M (Jun 2003). "Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression". The Journal of Biological Chemistry. 278 (26): 24132–8. doi:10.1074/jbc.M302283200. PMID 12711603.
  15. ↑ Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M (Nov 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nature Cell Biology. 6 (11): 1135–41. doi:10.1038/ncb1187. PMID 15502821.
  16. ↑ 16.0 16.1 Nielsen AL, Sanchez C, Ichinose H, Cerviño M, Lerouge T, Chambon P, Losson R (Nov 2002). "Selective interaction between the chromatin-remodeling factor BRG1 and the heterochromatin-associated protein HP1alpha". The EMBO Journal. 21 (21): 5797–806. doi:10.1093/emboj/cdf560. PMC 131057. PMID 12411497.
  17. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  18. ↑ Vassallo MF, Tanese N (Apr 2002). "Isoform-specific interaction of HP1 with human TAFII130". Proceedings of the National Academy of Sciences of the United States of America. 99 (9): 5919–24. doi:10.1073/pnas.092025499. PMC 122877. PMID 11959914.
  19. ↑ Cammas F, Oulad-Abdelghani M, Vonesch JL, Huss-Garcia Y, Chambon P, Losson R (Sep 2002). "Cell differentiation induces TIF1beta association with centromeric heterochromatin via an HP1 interaction". Journal of Cell Science. 115 (Pt 17): 3439–48. PMID 12154074.
  20. ↑ Hu X, Dutta P, Tsurumi A, Li J, Wang J, Land H, Li WX (Jun 2013). "Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth". Proc Natl Acad Sci U S A. 110 (25): 10213–10218. doi:10.1073/pnas.1221243110. PMC 3690839. PMID 23733954.

Further reading

External links

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