Bromodomain-containing protein: Difference between revisions

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'''Bromodomain-containing proteins''' (BRD) are active as histone acetyltransferase, chromatin remodeling and transcriptional mediation.  The bromodomain is a ca. 110 amino acid long sequence which recognizes acetylated lysine residues which are found in the C-terminal of histones<ref>PMID:11911891</ref>.
'''Bromodomain-containing proteins''' (BRD) are active as histone acetyltransferase, chromatin remodeling and transcriptional mediation.  The bromodomain is a ca. 110 amino acid long sequence which recognizes acetylated lysine residues which are found in the C-terminal of histones<ref>PMID:11911891</ref>.
   
*'''BRD1''' is essential for normal brain development<ref>PMID:35941107</ref>.
For detalis on BRD3 see [[Human bromodomain containing protein 3]]
*'''BRD2''' promotes spatial mixing and compartmentalisation of chromatin<ref>PMID:35410381</ref>.
*'''BRD3''' and '''BRD4''' regulate skeletal myogenesis<ref>PMID:28733670</ref>. For detalis on BRD3 see [[Human bromodomain containing protein 3]]
*'''BRD7''' promotes colorectal cancer by regulating the ubiquitin-proteasome-dependent stabilisation of c-Myc protein<ref>PMID:34109174</ref>.
*'''BRD9''' has a role in activation of interferon-stimulated genes<ref>PMID:34983841</ref>.


== Disease ==
== Disease ==
Line 12: Line 15:
== Structural highlights ==
== Structural highlights ==


<scene name='72/724778/Cv/3'>BRD4 bromodomain 1 inhibitors bind to the acetyl-binding pocket</scene><ref>PMID:18552174</ref>. Water molecules are shown as red spheres.
<scene name='72/724778/Cv/4'>BRD4 bromodomain 1 inhibitors bind to the acetyl-binding pocket</scene><ref>PMID:18552174</ref>. Water molecules are shown as red spheres.
 


</StructureSection>
== 3D Structures of bromodomain-containing protein ==
== 3D Structures of bromodomain-containing protein ==
[[Bromodomain-containing protein 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Bromodomain-containing protein 1
 
**[[3lyi]] – hBRD1 PWWP domain residues 925-1049 - human<br />
**[[2ku3]] – hBRD1 PHD1 zinc finger domain residues 208-269 - NMR<br />
**[[2lq6]] – hBRD1 PHD2 zinc finger domain residues 317-394 (mutant) - NMR<br />
**[[3l43]] – histone H3.3 N-terminal/hBRD1 PHD1 zinc finger domain - NMR<br />
**[[3rcw]], [[4z02]] – hBRD1 bromodomain residues 555-688<br />
**[[5pwb]], [[5pwa]], [[5pw9]], [[5pw8]], [[5pw7]], [[5pw6]], [[5pw5]], [[5pw4]], [[5pw3]], [[5pw2]], [[5pw1]], [[5pw0]], [[5pvz]], [[5pvy]], [[5pvx]], [[5pvw]], [[5pvv]], [[5pvu]], [[5pvt]], [[5pvs]], [[5pvr]], [[5pvq]], [[5pvp]], [[5pvo]], [[5pvn]], [[5pvm]], [[5pvl]], [[5pvk]], [[5pvj]], [[5pvi]], [[5pvh]], [[5pvg]], [[5pvf]], [[5pve]], [[5pvd]], [[5pvc]], [[5pvb]], [[5pva]], [[5pv9]], [[5pv8]], [[5pv7]], [[5pv6]], [[5pv5]], [[5pv4]], [[5pv3]], [[5pv2]], [[5pv1]], [[5pv0]], [[5puz]], [[5puy]], [[5pux]], [[5puw]], [[5puv]], [[5puu]], [[5put]], [[5pus]], [[5pur]], [[5puq]], [[5pup]], [[5pun]], [[5pum]], [[5puo]], [[5pul]], [[5puk]], [[5puj]], [[5pui]], [[5puh]], [[5pug]], [[5puf]], [[5pue]], [[5pud]], [[5puc]], [[5pub]], [[5pua]], [[5pu9]], [[5pu8]], [[5pu7]], [[5pu6]], [[5pu5]], [[5pu4]], [[5pu3]], [[5pu2]], [[5pu1]], [[5pu0]], [[5ptz]], [[5pty]], [[5ptx]], [[5ptw]], [[5ptv]], [[5ptu]], [[5pts]], [[5ptt]], [[5ptr]], [[5ptq]], [[5ptp]], [[5pto]], [[5ptn]], [[5ptm]], [[5ptl]], [[5ptk]], [[5ptj]], [[5pth]], [[5ptg]], [[5ptf]], [[5pte]], [[5ptd]], [[5ptc]], [[5ptb]], [[5pta]], [[5pt9]], [[5pt8]], [[5pt7]] – [[5pnx]] – hBRD1 bromodomain (mutant)<br />
**[[5n49]] – hBRD1 bromodomain + inhibitor<br />
**[[5ame]] – hBRD1 bromodomain+PHD (mutant) + piperazine derivative<br />
**[[5amf]] – hBRD1 bromodomain+PHD (mutant) + indazole derivative<br />
**[[5fg6]] – hBRD1 bromodomain+PHD + probe<br />
**[[4z02]] – hBRD1 PWWP domain + quinoline derivative<br />
 
*Bromodomain-containing protein 2
 
**[[1x0j]], [[2dvv]] – hBRD2 bromodomain 1<br />
**[[5hel]], [[5hem]], [[5hen]], [[5hfq]] – hBRD2 bromodomain 1 (mutant)<br />
**[[2g4a]] – hBRD2 residues 1-116 - NMR<br />
**[[5ibn]] – hBRD2 bromodomain 2 <br />
**[[4qeu]], [[5dfb]] – hBRD2 bromodomain 2 (mutant)<br />
 
*Bromodomain-containing protein 2 complex
 
**[[2dvq]], [[2dvr]], [[2dvs]], [[2e3k]] – hBRD2 bromodomain 1 + histone H4 peptide<br />
**[[3oni]] – hBRD2 residues 224-335 + inhibitor<br />
**[[3aqa]], [[2ydw]], [[2yek]], [[4a9e]], [[4a9f]], [[4a9h]], [[4a9i]], [[4a9j]], [[4a9m]], [[4a9n]], [[4a9o]], [[4alh]], [[4akn]], [[4alg]], [[4uyf]], [[4uyg]], [[4uyh]] – hBRD2 N-terminal bromodomain + inhibitor<br />
**[[4mr5]], [[4mr6]], [[4j1p]], [[5ig6]], [[5ek9]], [[5dw1]], [[5xhk]], [[5xhe]], [[5u6v]], [[5n2l]] – hBRD2 bromodomain 2 + inhibitor<br />
**[[5o3i]], [[5o3h]], [[5o3g]], [[5o3f]], [[5o3e]], [[5o3d]], [[5o3c]], [[5o3b]], [[5o3a]], [[5o39]], [[5o38]] – hBRD2 bromodomain 2 (mutant) + inhibitor<br />
**[[5u5s]] – hBRD2 bromodomain 2 + STAT3 peptide - NMR<br />
**[[5bt5]] – hBRD2 bromodomain 2 + probe<br />
**[[4qev]], [[4qew]] – hBRD2 bromodomain 2 (mutant) + probe<br />
**[[5dfc]], [[5dfd]] – hBRD2 bromodomain 2 (mutant) + ligand<br />
 
*Bromodomain-containing protein 3
 
**[[2nxb]] – hBRD3 bromodomain 1<br />
**[[2yw5]] – hBRD3 bromodomain 1 - NMR<br />
**[[3s91]], [[3s92]] – hBRD3 bromodomain 1 + inhibitor<br />
**[[2l5e]] – mBRD3 bromodomain 1 + GATA-1 C-terminal – mouse - NMR<br />
**[[2oo1]] – hBRD3 bromodomain 2<br />
**[[2e7n]] – hBRD3 bromodomain 2 - NMR<br />
**[[5hfr]] – hBRD3 bromodomain 2 (mutant)<br />
**[[5hjc]] – hBRD3 bromodomain 2+ histone H3.1 peptide<br />
**[[5a7c]] – hBRD3 bromodomain 2 + inhibitor<br />
**[[6bgh]] – hBRD3 ET domain + BRG1 peptide - NMR<br />
**[[6bgg]] – hBRD3 ET domain + CHD4 peptide - NMR<br />
 
*Bromodomain-containing protein 4
 
**[[2oss]], [[4j3i]], [[4lyi]], [[5hq7]], [[5hq6]], [[5hq5]] – hBRD4 bromodomain 1<br />
**[[2ouo]] – hBRD4 bromodomain 2<br />
**[[2i8n]] – hBRD4 bromodomain 2 - NMR<br />
**[[6bnh]] – hBRD4 ET domain + JMJD6 peptide - NMR<br />
**[[3jvj]] – mBRD4 bromodomain 1<br />
**[[2dww]], [[3jvl]], [[3jvm]] – mBRD4 bromodomain 2<br />
**[[2jns]] – mBRD4 ET domain - NMR<br />
 
*Bromodomain-containing protein 4 bromodomain 1 complex
 
**[[3jvk]], [[3muk]], [[3mul]] – mBRD4 bromodomain 1 + histone H3.3 peptide<br />
**[[3uvw]], [[3uvy]], [[3uvx]], [[3uw9]] – hBRD4 bromodomain 1 + histone H4 peptide<br />
**[[4kv1]] – hBRD4 bromodomain 1 + Rel peptide<br />
**[[3mxf]] – mBRD4 bromodomain 1 + inhibitor<br />
**[[3p5o]], [[2yel]], [[3zyu]], [[3u5j]], [[3u5k]], [[3u5l]], [[4a9l]], [[4e96]], [[4f3i]], [[4hxk]], [[4hxl]], [[4hxm]], [[4hxn]], [[4hxo]], [[4hxp]], [[4hxr]], [[4hxs]], [[4lr6]], [[4lrg]], [[3svf]], [[3svg]], [[4gpj]], [[4hbv]], [[4hbw]], [[4hbx]], [[4hby]], [[4don]], [[4j0r]], [[4j0s]], [[4bw1]], [[4bw2]], [[4bw3]], [[4bw4]], [[4men]], [[4meo]], [[4mep]], [[4meq]], [[4bjx]], [[4c66]], [[4c67]], [[4ioo]], [[4ioq]], [[4ior]], [[4mr3]], [[4mr4]], [[4nqm]], [[4nr8]], [[4cfk]], [[4cfl]], [[4lyw]], [[4ogi]], [[4ogj]], [[4o70]], [[4o71]], [[4o72]], [[4o74]], [[4o75]], [[4o76]], [[4o77]], [[4o78]], [[4o7a]], [[4o7b]], [[4o7c]], [[4o7e]], [[4o7f]], [[4ps5]], [[4nuc]], [[4nue]], [[4nud]], [[4pce]], [[4pci]], [[4uyd]], [[4qzs]], [[4wiv]], [[4cl9]], [[4clb]], [[4xy9]], [[4xya]], [[4z1q]], [[4z1s]], [[4uix]], [[4uiy]], [[4uiz]], [[4qr3]], [[4qr4]], [[4qr5]], [[5bt4]], [[5a5s]], [[5a85]], [[5acy]], [[4x2i]], [[4zc9]], [[5fbx]], [[4yh3]], [[4yh4]], [[5coi]], [[5cp5]], [[5cpe]], [[5cqt]], [[5crm]], [[5crz]], [[5cs8]], [[5ctl]], [[5cy9]], [[5d0c]], [[5dx4]], [[4lzs]], [[5d24]], [[5d25]], [[5d26]], [[5d3h]], [[5d3j]], [[5d3l]], [[5d3n]], [[5d3p]], [[5d3r]], [[5d3s]], [[5d3t]], [[5egu]], [[5ei4]], [[5eis]], [[5hls]], [[5hm0]], [[5ku3]], [[5khm]], [[5i88]], [[5i80]], [[5f63]], [[5f62]], [[5f61]], [[5f60]], [[5e0r]], [[5dw2]], [[5dlz]], [[5dlx]], [[5cfw]], [[5ad3]], [[5ad2]], [[4zw1]], [[5u2f]], [[5u2e]], [[5u28]], [[5luu]], [[5lj2]], [[5lj1]], [[5y1y]], [[5wuu]], [[5vom]], [[5v67]], [[5uvw]], [[5ula]], [[5ti7]], [[5n2m]], [[5mli]], [[5mkz]]], [[5m3a]], [[5m39]], [[5lrq]], [[5kj0]], [[5kdh]], [[5h21]], [[5f5z]] – hBRD4 bromodomain 1 + inhibitor<br />
**[[5z9c]] – hBRD4 bromodomain 1 + inhibitor - NMR<br />
**[[5ti6]], [[5ti5]], [[5ti4]], [[5ti3]], [[5ti2]] – hBRD4 bromodomain 1 (mutant) + inhibitor <br />
**[[4lys]], [[4lzr]] – hBRD4 bromodomain 1 + colchiceine<br />
**[[4qb3]] – hBRD4 bromodomain 1 + olinone<br />
**[[4whw]] – hBRD4 bromodomain 1 + probe<br />
**[[5igk]] – hBRD4 bromodomain 1 + bromosporine<br />
**[[5hcl]] – hBRD4 bromodomain 1 + drug<br />
 
*Bromodomain-containing protein 4 bromodomain 2 complex
 
**[[2yem]], [[4z93]], [[5u2c]], [[5jwm]], [[5uvz]], [[5uvy]], [[5uvx]], [[5uvv]], [[5uvu]], [[5uvt]], [[5uvs]], [[5uoo]], [[5uf0]], [[5uez]], [[5uey]], [[5uex]], [[5uew]], [[5uev]], [[5ueu]], [[5uet]], [[5ues]], [[5uer]], [[5ueq]], [[5uep]], [[5ueo]] – hBRD4 bromodomain 2 + inhibitor<br />
**[[2lsp]] – hBRD4 bromodomain 2 + Nf-Kb peptide<br />
**[[4kv4]] – hBRD4 bromodomain 2 + Rel peptide<br />
**[[2mjv]] – hBRD4 bromodomain 2 + Twist peptide<br />
**[[5t35]] – hBRD4 bromodomain 2 + ELOB + ELOC + PVHL peptide<br />
 
*Bromodomain-containing protein 7
 
**[[5mq1]] – hBRD7 bromodomain + inhibitor<br />
 
*Bromodomain-containing protein 9
 
**[[3hme]] – hBRD9 bromodomain <br />
**[[5ji8]] – hBRD9 JUS-SPRY domain <br />
**[[5ign]] – hBRD9 bromodomain + L999 <br />
**[[5igm]] – hBRD9 bromodomain + bromosporine <br />
**[[4nqn]], [[4xy8]], [[4z6h]], [[4z6i]], [[5e9v]], [[5f2p]], [[5f25]], [[5f1l]], [[5f1h]], [[5eu1]], [[5mky]] – hBRD9 bromodomain + inhibitor<br />
**[[4yy4]] – hBRD9 bromodomain + DMSO<br />
**[[4yy6]], [[4yyd]], [[4yyg]], [[4yyh]], [[4yyj]], [[4yyk]], [[4yyi]] – hBRD9 bromodomain + histone H4 peptide<br />
**[[4uit]], [[4uiu]], [[4uiv]], [[4uiw]] – hBRD9 JUS-SPRY domain + inhibitor<br />
**[[5i7y]], [[5i7x]], [[5i40]] – hBRD9 JUS-SPRY domain + inhibitor<br />
**[[5twx]] – hBRD9 bromodomain residues 134-250 + heterobifunctional ligand<br />
}}
 
 


== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 09:43, 2 June 2024

Function

Bromodomain-containing proteins (BRD) are active as histone acetyltransferase, chromatin remodeling and transcriptional mediation. The bromodomain is a ca. 110 amino acid long sequence which recognizes acetylated lysine residues which are found in the C-terminal of histones[1].

  • BRD1 is essential for normal brain development[2].
  • BRD2 promotes spatial mixing and compartmentalisation of chromatin[3].
  • BRD3 and BRD4 regulate skeletal myogenesis[4]. For detalis on BRD3 see Human bromodomain containing protein 3
  • BRD7 promotes colorectal cancer by regulating the ubiquitin-proteasome-dependent stabilisation of c-Myc protein[5].
  • BRD9 has a role in activation of interferon-stimulated genes[6].

Disease

Dysfunction of BRD is involved in cancer, inflammation, obesity and multiple sclerosis[7]. BRD4 translocations are detected in NUT midline carcinoma and a variety of BRD4 inhibitors are clinically tested at the present[8].

Structural highlights

[9]. Water molecules are shown as red spheres.


3D Structures of bromodomain-containing protein

Bromodomain-containing protein 3D structures


Human bromodomain-containing protein 4 bromodomain 1 complex with inhibitor and ethylene glycol (PDB code 3p5o)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Zeng L, Zhou MM. Bromodomain: an acetyl-lysine binding domain. FEBS Lett. 2002 Feb 20;513(1):124-8. PMID:11911891
  2. ↑ Paternoster V, Cömert C, Kirk LS, la Cour SH, Fryland T, Fernandez-Guerra P, Stougaard M, Nyengaard JR, Qvist P, Bross P, Børglum AD, Christensen JH. The psychiatric risk gene BRD1 modulates mitochondrial bioenergetics by transcriptional regulation. Transl Psychiatry. 2022 Aug 8;12(1):319. PMID:35941107 doi:10.1038/s41398-022-02053-2
  3. ↑ Xie L, Dong P, Qi Y, Hsieh TS, English BP, Jung S, Chen X, De Marzio M, Casellas R, Chang HY, Zhang B, Tjian R, Liu Z. BRD2 compartmentalizes the accessible genome. Nat Genet. 2022 Apr;54(4):481-491. PMID:35410381 doi:10.1038/s41588-022-01044-9
  4. ↑ Roberts TC, Etxaniz U, Dall'Agnese A, Wu SY, Chiang CM, Brennan PE, Wood MJA, Puri PL. BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis. Sci Rep. 2017 Jul 21;7(1):6153. PMID:28733670 doi:10.1038/s41598-017-06483-7
  5. ↑ Zhao R, Liu Y, Wu C, Li M, Wei Y, Niu W, Yang J, Fan S, Xie Y, Li H, Wang W, Zeng Z, Xiong W, Li X, Li G, Zhou M. BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer. Front Cell Dev Biol. 2021 May 24;9:659392. PMID:34109174 doi:10.3389/fcell.2021.659392
  6. ↑ Ahmed NS, Gatchalian J, Ho J, Burns MJ, Hah N, Wei Z, Downes M, Evans RM, Hargreaves DC. BRD9 regulates interferon-stimulated genes during macrophage activation via cooperation with BET protein BRD4. Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2110812119. PMID:34983841 doi:10.1073/pnas.2110812119
  7. ↑ Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer. 2012 Jun 22;12(7):465-77. doi: 10.1038/nrc3256. PMID:22722403 doi:http://dx.doi.org/10.1038/nrc3256
  8. ↑ French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol. 2010 Jun;63(6):492-6. doi: 10.1136/jcp.2007.052902. Epub 2008 Jun , 13. PMID:18552174 doi:http://dx.doi.org/10.1136/jcp.2007.052902
  9. ↑ French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol. 2010 Jun;63(6):492-6. doi: 10.1136/jcp.2007.052902. Epub 2008 Jun , 13. PMID:18552174 doi:http://dx.doi.org/10.1136/jcp.2007.052902

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