{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P45973","secondaryAccessions":["B2R8T9"],"uniProtkbId":"CBX5_HUMAN","entryAudit":{"firstPublicDate":"1995-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1995-11-01","entryVersion":232,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Chromobox protein homolog 5"}},"alternativeNames":[{"fullName":{"value":"Antigen p25"}},{"fullName":{"value":"Heterochromatin protein 1 homolog alpha"},"shortNames":[{"value":"HP1 alpha"}]}]},"genes":[{"geneName":{"value":"CBX5"},"synonyms":[{"value":"HP1A"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16127177"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19783980"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20231385"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40440427"}],"value":"Component of heterochromatin that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression (PubMed:40440427). In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph) (PubMed:19783980). Also recognizes and binds histone H1.4 methylated at 'Lys-26' (H1.4K26me) (PubMed:16127177). Excluded from chromatin when histone H1.4 is Simultaneously methylated at Lys-26 (H1.4K26me) and phosphorylated at Ser-27 (H1.4S27Ph) (PubMed:16127177). May contribute to the association of heterochromatin with the inner nuclear membrane by interactions with the lamin-B receptor (LBR) (PubMed:19783980). Involved in the formation of kinetochore through interaction with the MIS12 complex subunit NSL1 (PubMed:19783980, PubMed:20231385). Required for the formation of the inner centromere (PubMed:20231385)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61686"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11242053"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11313457"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15502821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15882967"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15899859"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19617346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19666599"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19710015"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20042602"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20231385"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20562864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20819937"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20850016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21047797"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21199919"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21346195"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23542155"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25906157"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28977666"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32051553"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40440427"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9169472"}],"value":"Homodimer (PubMed:20819937). Interacts with histone H3 methylated at 'Lys-9' (PubMed:11242053, PubMed:21047797). Interacts (via Chromo 2; shadow subtype domain) with the MIS12 complex subunit NSL1; the interaction is direct, involves dimeric CBX5, and occurs during interphase (PubMed:15502821, PubMed:20231385, PubMed:20819937). Interacts with POGZ; POGZ and PXVXL motif-containing proteins such as INCENP and TRIM28 compete for interaction with CBX5 (PubMed:20562864, PubMed:20850016, PubMed:21346195). Interacts with LRIF1 (via PxVxL motif) (PubMed:23542155). Interacts with INCENP (PubMed:20562864). Interacts with TRIM24 (PubMed:11313457). Interacts (via the chromoshadow domain) with ATRX; the interaction is direct (PubMed:15882967). Interacts (via the chromoshadow domain) with CHAF1A; the interaction is direct (PubMed:15882967). Interacts (via the chromoshadow domain) with LBR; the interaction is direct (PubMed:15882967, PubMed:9169472). Interacts (via the chromoshadow domain) with NIPBL; the interaction is direct (PubMed:15882967). Interacts (via the chromoshadow domain) with SP100; the interaction is direct (PubMed:15882967). Interacts (via the chromoshadow domain) with STAM2; the interaction is direct (PubMed:15882967). Interacts (via the chromoshadow domain) with TRIM28; the interaction is direct (PubMed:15882967). Interacts (via the chromoshadow domain) with CBX3; the interaction is direct (PubMed:9169472). Interacts with PRR14 (via N-terminus) (PubMed:25906157). Interacts with RRP1B (PubMed:19710015). Interacts with HNRNPU (via C-terminus); this interaction is, at least in part, RNA-dependent (PubMed:19617346). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553). Interacts with AURKB during mitosis (PubMed:20231385). Interacts with CHAMP1 (PubMed:20850016). Interacts with BAHD1 (PubMed:19666599). Interacts with HP1BP3 (PubMed:20042602). Interacts with CHD3 (PubMed:28977666). Interacts with CHD4 (PubMed:28977666). Interacts with SMYD5 (By similarity). Interacts with KMT5B (By similarity). Interacts with KMT5C (By similarity). Interacts with ASB7 (via PxVxL motif 1); leading to ASB7 recruitment to heterochromatin (PubMed:40440427)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15864296"}],"value":"(Microbial infection) Interacts with JC virus agnoprotein; this interaction induces the dissociation of CBX5 from LBR, resulting in destabilization of the nuclear envelope"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q9H2P0","geneName":"ADNP","intActId":"EBI-1764854"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q9NP61","geneName":"ARFGAP3","intActId":"EBI-2875816"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"O75143-2","geneName":"ATG13","intActId":"EBI-20151086"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P46100","geneName":"ATRX","intActId":"EBI-396461"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q8TBE0","geneName":"BAHD1","intActId":"EBI-742750"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P45973","geneName":"CBX5","intActId":"EBI-78219"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q13111","geneName":"CHAF1A","intActId":"EBI-1020839"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P48730-2","geneName":"CSNK1D","intActId":"EBI-9087876"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q9UMR2","geneName":"DDX19B","intActId":"EBI-719232"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P09471","geneName":"GNAO1","intActId":"EBI-715087"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P84243","geneName":"H3-3B","intActId":"EBI-120658"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q16695","geneName":"H3-4","intActId":"EBI-358900"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P68431","geneName":"H3C12","intActId":"EBI-79722"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P62805","geneName":"H4C9","intActId":"EBI-302023"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q9NQS7","geneName":"INCENP","intActId":"EBI-307907"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P28838","geneName":"LAP3","intActId":"EBI-2339312"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q14739","geneName":"LBR","intActId":"EBI-1055147"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q8N448","geneName":"LNX2","intActId":"EBI-2340947"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q5T3J3","geneName":"LRIF1","intActId":"EBI-473196"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q9UIS9","geneName":"MBD1","intActId":"EBI-867196"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q14728","geneName":"MFSD10","intActId":"EBI-11337904"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"P01106","geneName":"MYC","intActId":"EBI-447544"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P45973","intActId":"EBI-78219"},"interactantTwo":{"uniProtKBAccession":"Q9BZ95","geneName":"NSD3","intActId":"EBI-3390132"},"numberOfExperiments":2,"organismDiffer":false},{"intera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Component of centromeric and pericentromeric heterochromatin. Associates with chromosomes during mitosis (PubMed:40440427). Associates specifically with chromatin during metaphase and anaphase (PubMed:19617346). Localizes to sites of DNA damage (PubMed:28977666)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10460410"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19617346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28977666"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10460410"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40440427"}],"value":"Chromosome","id":"SL-0468"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10460410"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20231385"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21346195"}],"value":"Chromosome, centromere","id":"SL-0047"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10460410"}],"value":"Phosphorylation of HP1 and LBR may be responsible for some of the alterations in chromatin organization and nuclear structure which occur at various times during the cell cycle (By similarity). Phosphorylated during interphase and possibly hyper-phosphorylated during mitosis"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20498703"}],"value":"Ubiquitinated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"19880879"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"25750265"}],"value":"Was previously reported to interact with ASXL1. However, this publication has been retracted"}],"commentType":"CAUTION"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":191,"modifier":"EXACT"}},"description":"Chromobox protein homolog 5","featureId":"PRO_0000080208"},{"type":"Domain","location":{"start":{"value":20,"modifier":"EXACT"},"end":{"value":78,"modifier":"EXACT"}},"description":"Chromo 1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00053"}]},{"type":"Domain","location":{"start":{"value":121,"modifier":"EXACT"},"end":{"value":179,"modifier":"EXACT"}},"description":"Chromo 2; shadow subtype","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00053"}]},{"type":"Region","location":{"start":{"value":70,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional 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