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Details on Person UniProt:P25440 BRD2
| Class:Id | ReferenceGeneProduct:50956 |
|---|---|
| _chainChangeLog | chain:1-801 added on Sat February 7 2015 |
| _displayName | UniProt:P25440 BRD2 |
| _timestamp | 2024-11-03 20:09:03 |
| chain | chain:1-801 |
| checksum | 9A075EEB13507D8E |
| comment | FUNCTION Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures (PubMed:17148447, PubMed:17848202, PubMed:18406326, PubMed:20048151, PubMed:20709061, PubMed:20871596). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:28262505). Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation (PubMed:35410381). Also recognizes and binds acetylated non-histone proteins, such as STAT3 (PubMed:28262505). Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin (PubMed:28262505). In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000).ACTIVITY REGULATION Inhibited by JQ1, a thieno-triazolo-1,4-diazepine derivative, which specifically inhibits members of the BET family (BRD2, BRD3 and BRD4) (PubMed:20871596). The first bromo domain is inhibited by GSK778 (iBET-BD1), which specifically inhibits the first bromo domain of members of the BET family (BRD2, BRD3 and BRD4) (PubMed:32193360). The second bromo domain is inhibited by ABBV-744, which specifically inhibits the second bromo domain of members of the BET family (BRD2, BRD3 and BRD4) (PubMed:31969702). The second bromo domain is inhibited by GSK046 (iBET-BD2), which specifically inhibits the second bromo domain of members of the BET family (BRD2, BRD3 and BRD4) (PubMed:32193360).SUBUNIT Homodimer (PubMed:17148447, PubMed:17848202, PubMed:20048151, PubMed:20709061). Interacts with E2F1 (PubMed:17148447). Interacts with (acetylated) STAT3; promoting STAT3 recruitment to chromatin (PubMed:28262505). Interacts with CTCF; promoting BRD2 recruitment to chromatin (By similarity).SUBUNIT (Microbial infection) Interacts with herpes virus 8 protein LANA1.INTERACTION Detected on chromatin and nucleosomes.ALTERNATIVE PRODUCTS The first bromo domain specifically recognizes histone H4 acetylated at 'Lys-12' (H4K12ac) (PubMed:20048151). It also specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). The second bromo domain recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively) (PubMed:20709061).MISCELLANEOUS Some specific inhibitors of BRD2 that prevent binding to acetylated histone are promising therapeutic molecules for the treatment of cancers or inflammatory diseases (PubMed:31969702, PubMed:32193360). ABBV-744, a small molecule, has been tested on tumors with success: ABBV-744 antiproliferative activity is mainly restricted to cell lines of acute myeloid leukaemia and prostate cancer and is able to displace BRD4 from chromatin (PubMed:31969702). GSK046 (iBET-BD2), which specifically inhibits the second bromo domain, is a promising therapeutic small molecule for the treatment of inflammatory and autoimmune diseases (PubMed:32193360).SIMILARITY Belongs to the BET family.SEQUENCE CAUTION Truncated N-terminus. |
| description | recommendedName: fullName evidence="26"Bromodomain-containing protein 2 alternativeName: O27.1.1 |
| geneName | BRD2 KIAA9001 RING3 |
| identifier | P25440 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Bromodomain Chromatin regulator Chromosome Host-virus interaction Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transcription Transcription regulation |
| modified | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | BRD2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8995308] ENSEMBL:ENSG00000204256 BRD2 [Homo sapiens] |
| secondaryIdentifier | BRD2_HUMAN A2AAU0 B0S7P0 B1AZT1 O00699 O00700 Q15310 Q5STC9 Q63HQ9 Q658Y7 Q6P3U2 Q969U4 |
| sequenceLength | 801 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:220254] UniProt:P25440-2 BRD2 [Homo sapiens] [ReferenceIsoform:403442] UniProt:P25440-1 BRD2 [Homo sapiens] [ReferenceIsoform:8968204] UniProt:P25440-3 BRD2 [Homo sapiens] [ReferenceIsoform:8968205] UniProt:P25440-4 BRD2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:8951979] BRD2 [nucleoplasm] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P25440 BRD2 (50956)
