https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Elizabeth+CookProteopedia - User contributions [en]2026-09-15T21:06:46ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334515User:Elizabeth Cook/Sandbox 12025-05-01T05:29:45Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix_2/1'>αZ, αA, αB, αC</scene>), and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a <scene name='10/1079536/Helix_2/2'>hydrophobic shelf</scene> found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is also hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone-bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, <scene name='10/1079536/Cpd6/1'>Cpd6</scene>, an acetyllysine mimetic, has been synthesized and studied. The inhibitor is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form, and <scene name='10/1079536/D464/1'>D464</scene> in which there is one direct H-bond and one coordinated through water. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334514User:Elizabeth Cook/Sandbox 12025-05-01T05:19:04Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix_2/1'>αZ, αA, αB, αC</scene>), and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a <scene name='10/1079536/Helix_2/2'>hydrophobic shelf</scene> found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is also hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone-bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, <scene name='10/1079536/Cpd6/1'>Cpd6</scene>, an acetyllysine mimetic, has been synthesized and studied. The inhibitor is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334513User:Elizabeth Cook/Sandbox 12025-05-01T05:17:55Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix_2/1'>αZ, αA, αB, αC</scene>), and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a <scene name='10/1079536/Helix_2/2'>hydrophobic shelf</scene> found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is also hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone-bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6, an acetyllysine mimetic, has been synthesized and studied. The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334512User:Elizabeth Cook/Sandbox 12025-05-01T05:16:19Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix_2/1'>αZ, αA, αB, αC</scene>), and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a <scene name='10/1079536/Helix_2/2'>hydrophobic shelf</scene> found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is also hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone-bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334511User:Elizabeth Cook/Sandbox 12025-05-01T05:02:29Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix_2/1'>αZ, αA, αB, αC</scene>), and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a <scene name='10/1079536/Helix_2/2'>hydrophobic shelf</scene> found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is also hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone-bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334510User:Elizabeth Cook/Sandbox 12025-05-01T05:00:48Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix_2/1'>αZ, αA, αB, αC</scene>), and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a <scene name='10/1079536/Helix_2/2'>hydrophobic shelf</scene> found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is also hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone-bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334508User:Elizabeth Cook/Sandbox 12025-05-01T04:38:36Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|left|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334507User:Elizabeth Cook/Sandbox 12025-05-01T04:37:39Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. [[Image:Higherorderchromatin.png|thumb|right|200px|]]<br />
<br />
Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
[[Image:Postptms.png|center|600px]]<br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334506User:Elizabeth Cook/Sandbox 12025-05-01T04:20:52Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4334505User:Elizabeth Cook/Sandbox 12025-05-01T04:19:38Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 BRD in complex with Cpd6 inhibitor' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |300px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |300px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332447User:Elizabeth Cook/Sandbox 12025-04-29T14:32:27Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |300px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |300px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332443User:Elizabeth Cook/Sandbox 12025-04-29T14:17:05Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |300px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |300px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332440User:Elizabeth Cook/Sandbox 12025-04-29T14:01:32Z<p>Elizabeth Cook: </p>
<hr />
<div>== '''Cat Eye Syndrome Chromosome Region Candidate 2''' ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332393User:Elizabeth Cook/Sandbox 12025-04-29T08:53:38Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D464 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332392User:Elizabeth Cook/Sandbox 12025-04-29T08:41:18Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D646 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<br />
The <scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> is coordinated by the conserved <scene name='10/1079536/N514/1'>N514</scene> in which <scene name='10/1079536/2_bonds/1'>2 direct H-bonds</scene> form. <br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332391User:Elizabeth Cook/Sandbox 12025-04-29T08:37:59Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Abnormal regulation of CECR2 has been linked to several diseases. It was first studied in connection with Cat Eye Syndrome, a rare congenital disorder caused by duplication of a region on chromosome 22 that includes CECR2, leading to developmental abnormalities. More recently, CECR2 has been implicated in cancer, particularly in breast cancer metastasis, where it appears to promote tumor cell invasion and immune system evasion by altering gene expression patterns. Because CECR2 influences chromatin structure and gene activity, its dysregulation can have wide-ranging effects on development, immune response, and cancer progression, making it an important target for further research and potential therapies. CECR2 is an attractive drug target because of its bromodomain, as bromodomains already have many small molecule inhibitors in use clinically.<br />
<br />
In efforts to develop new small molecule inhibitors for the CECR2 bromodomain, Cpd6 has been found and studied. <br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
Cpd6 makes contacts to CECR2 through N514 (2 direct H-bonds) and D646 (1 direct H-bond, and 1 H-bond coordinated by water). <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332390User:Elizabeth Cook/Sandbox 12025-04-29T08:28:53Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
CECR2 has multiple 100% sequence alignment matches across various species, indicative of its importance and how well it has been conserved, particularly the bromodomain. This provides insight into the essential biological roles performed by CECR2 that have remained critical across millions of years of evolution. The high similarity across different species suggest that even small changes could be harmful, meaning CECR2 is fundamental to processes like DNA replication and gene regulation. <br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
In addition to being sequentially conserved, CECR2 is also structurally conserved, particularly within the binding pocket. Conservation of structure is indicative of the structural properties being crucial for CECR2’s function and that the mechanism in which it functions is critical across species. <br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Diseases found<br />
<br />
inhibition with small molecule<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332389User:Elizabeth Cook/Sandbox 12025-04-29T07:33:36Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
100% match, indicative of its importance<br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
It is also structurally conserved, function, mechanism is important<br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound CECR2, it can be assumed that it binds in a similar fashion to other bromodomains, considering the high levels of conservation amongst bromodomain-containing proteins. <br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Diseases found<br />
<br />
inhibition with small molecule<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332388User:Elizabeth Cook/Sandbox 12025-04-29T07:31:13Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
100% match, indicative of its importance<br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
It is also structurally conserved, function, mechanism is important<br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene>, N514 for CECR2, located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix (WPF in CECR2). There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic, although it is Y520 in CECR2. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound, we can assume (ref)<br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Diseases found<br />
<br />
inhibition with small molecule<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332387User:Elizabeth Cook/Sandbox 12025-04-29T07:28:15Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
100% match, indicative of its importance<br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
It is also structurally conserved, function, mechanism is important<br />
<br />
== Bromodomains ==<br />
<br />
The organization and compaction of DNA relies on the fundamental unit of chromatin, the nucleosome. The nucleosome is composed of an octamer of positively charged histone proteins that negatively charged DNA wraps around. Epigenetic modifications are a mechanism for gene regulation in which chemical modifications are added to histone proteins or DNA without altering the underlying DNA sequence. For example, acetylated lysine residues are an epigenetic signal found on the tails of histone proteins that are associated with an up-regulation of gene expression. The negative charge found on the acetyl group neutralizes the positive charge of the lysine residue, disrupting electrostatic interactions, allowing for a more open chromatin state. This allows for increased access to DNA for transcription factors and coactivators. <br />
<br />
Bromodomains are well characterized and known to recognize acetylated lysine residues. In doing so, the proteins that contain bromodomains are able to respond the information they receive from the epigenetic "signal" via various other domains. These proteins can call upon various regulatory complexes including writers, easers, and transcription factors. <br />
<br />
CECR2 is shown to recognize various acetyl post-translational modifications, singly and combinatorically, on the tails of histone H3 and H4. <br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene> located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound, we can assume (ref)<br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Diseases found<br />
<br />
inhibition with small molecule<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332386User:Elizabeth Cook/Sandbox 12025-04-29T05:28:02Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
100% match, indicative of its importance<br />
<br />
[[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
It is also structurally conserved, function, mechanism is important<br />
<br />
== Bromodomains ==<br />
<br />
Acetyllysine on histones (how and what)<br />
<br />
Meaning, bromodomain function<br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene> located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
While there is no solved structure for histone bound, we can assume (ref)<br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
Diseases found<br />
<br />
inhibition with small molecule<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332385User:Elizabeth Cook/Sandbox 12025-04-29T05:21:59Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
The full-length CECR2 is composed of an N-terminus DDT domain (DNA-binding homeobox and different transcription factors), an AT-hook, and a bromodomain.<ref>DOI: 10.1074/jbc.RA120.014598 </ref><ref>DOI: 10.1387/ijdb.092933jc</ref>The DDT and the AT-hook domain bind DNA, while the bromodomain recognizes acetylated lysine.<ref>DOI: 10.1093/nar/26.19.4413.</ref><ref>DOI: 10.1111/jipb.12069 From NLM Medline.</ref><ref>DOI: 10.1016/j.cell.2012.02.013</ref><br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]][[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene> located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332384User:Elizabeth Cook/Sandbox 12025-04-29T05:15:24Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]][[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene> located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly.<ref>PMID:27769355</ref><br />
<br />
<br />
== Disease and Therapeutics ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332383User:Elizabeth Cook/Sandbox 12025-04-29T05:11:47Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]][[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514_part_2/1'>conserved asparagine</scene> located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a <scene name='10/1079536/Gatekeeper/1'>gatekeeper residue</scene> that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<scene name='10/1079536/N514/1'>conserved asparagine</scene><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332372User:Elizabeth Cook/Sandbox 12025-04-29T04:49:04Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]][[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the <scene name='10/1079536/N514/1'>conserved asparagine</scene> located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a gatekeeper residue that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332370User:Elizabeth Cook/Sandbox 12025-04-29T04:46:54Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]][[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
Bromodomains are composed of 4 alpha helices (<scene name='10/1079536/Helix/1'>αZ, αA, αB, αC)</scene>, and 2 loops (ZA and BC). There are typically 4 conserved water molecules found within the acetyllysine binding pocket of the bromodomain. The two loops contain the majority of the residues responsible for ligand coordination, including the conserved asparagine located in the BC loop. In addition, there is a hydrophobic shelf found before the before the ZA loop and following αZ helix. There is also a gatekeeper residue that corresponds to the first residue found in the αC that is usually hydrophobic. Histone acetyllysines form a hydrogen bond with the conserved asparagine of bromodomains while various other residues make polar contacts to stabilize the interaction, directly or indirectly. <br />
<br />
== Disease and Therapeutics ==<br />
<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332365User:Elizabeth Cook/Sandbox 12025-04-29T03:48:10Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]][[Image:Conserved_cecr2.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:Conserved_cecr2.jpg&diff=4332364File:Conserved cecr2.jpg2025-04-29T03:47:17Z<p>Elizabeth Cook: </p>
<hr />
<div></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332362User:Elizabeth Cook/Sandbox 12025-04-29T03:46:44Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |500px|]]<br />
<br />
== Bromodomains ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332359User:Elizabeth Cook/Sandbox 12025-04-29T03:46:14Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
[[Image:Msa.jpg |300px|]]<br />
<br />
== Bromodomains ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:Msa.jpg&diff=4332358File:Msa.jpg2025-04-29T03:44:58Z<p>Elizabeth Cook: </p>
<hr />
<div></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332315User:Elizabeth Cook/Sandbox 12025-04-29T02:08:48Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
CECR2 is composed of a DDT domain, an AT hook, an NLS, and a bromodomain.<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332314User:Elizabeth Cook/Sandbox 12025-04-29T02:03:36Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332313User:Elizabeth Cook/Sandbox 12025-04-29T02:02:50Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <br />
<br />
== CECR2 Bromodomain ==<br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
<scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332311User:Elizabeth Cook/Sandbox 12025-04-29T02:01:17Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg|400px|]]<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332309User:Elizabeth Cook/Sandbox 12025-04-29T02:00:25Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
[[Image:CECR2 domain org.jpg]]<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:CECR2_domain_org.jpg&diff=4332306File:CECR2 domain org.jpg2025-04-29T01:57:26Z<p>Elizabeth Cook: </p>
<hr />
<div></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332304User:Elizabeth Cook/Sandbox 12025-04-29T01:55:37Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
The Cat Eye Syndrome Chromosome Region Candidate 2 (CECR2) is the regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes that modulate nucleosome spacing and DNA accessibility during replication and transcription.<ref>PMID:15640247</ref><ref>PMID:22464331</ref><ref>PMID:26365797</ref><ref>PMID:28801535</ref>. CECR2 also plays a key role in the DNA damage repair response, as it inhibits γ-H2AX activity.<ref>PMID:22699752</ref>. CECR2 is involved in various processes during development, including embryogenesis and spermatogenesis.<ref>PMID:22464331,</ref><ref>PMID:26365797</ref>. Recent studies have identified CECR2 as an epigenetic regulator of NF-kB pro-inflammatory gene expression through the recognition of acetylated RelA and driving breast cancer metastasis.<ref>PMID:35108062</ref><br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332298User:Elizabeth Cook/Sandbox 12025-04-29T01:18:10Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. N514, D464, Y520 (no contact) <ref>PMID:28740608</ref><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332297User:Elizabeth Cook/Sandbox 12025-04-29T01:16:38Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.png|center|400px|]]<br />
These contacts in CECR2. <ref>PMID:28740608</ref><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:Cecr2_contacts.png&diff=4332296File:Cecr2 contacts.png2025-04-29T01:15:58Z<p>Elizabeth Cook: </p>
<hr />
<div></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332256User:Elizabeth Cook/Sandbox 12025-04-28T23:40:45Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.jpg|center|400px|]]<br />
These contacts in CECR2. <ref>PMID:28740608</ref><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332255User:Elizabeth Cook/Sandbox 12025-04-28T23:39:50Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
[[Image:Cecr2_contacts.jpg|center|400px|alt=These contacts in CECR2. <ref>PMID:28740608</ref> ]]<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332254User:Elizabeth Cook/Sandbox 12025-04-28T23:38:22Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
These contacts in CECR2. [[Image:Cecr2_contacts.jpg|center|400px|]]<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332253User:Elizabeth Cook/Sandbox 12025-04-28T23:35:20Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
These contacts in CECR2. [[Image:Cecr2_contacts.jpg]]<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:Cecr2_contacts.jpg&diff=4332252File:Cecr2 contacts.jpg2025-04-28T23:33:35Z<p>Elizabeth Cook: </p>
<hr />
<div><ref> PMID: 28740608 <ref><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:Cecr2_contacts.jpg&diff=4332251File:Cecr2 contacts.jpg2025-04-28T23:32:31Z<p>Elizabeth Cook: </p>
<hr />
<div><ref> PMID: 28740608 <ref></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=File:Cecr2_contacts.jpg&diff=4332250File:Cecr2 contacts.jpg2025-04-28T23:31:27Z<p>Elizabeth Cook: </p>
<hr />
<div></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332246User:Elizabeth Cook/Sandbox 12025-04-28T23:24:06Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
== Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cookhttps://proteopedia.org/index.php?title=User:Elizabeth_Cook/Sandbox_1&diff=4332242User:Elizabeth Cook/Sandbox 12025-04-28T23:23:30Z<p>Elizabeth Cook: </p>
<hr />
<div>== Cat Eye Syndrome Chromosome Region Candidate 2 ==<br />
<br />
<StructureSection load='5V84' size='340' side='right' caption='PDB ID: 5V84. CECR2 in complex with Cpd6' scene=''><br />
<br />
Jmol <ref>PMID:21638687</ref><br />
<br />
== Function ==<br />
<br />
== Domain Organization ==<br />
<br />
== Sequential and Structural Conservation ==<br />
<br />
== Bromodomains ==<br />
<br />
== CECR2 Bromodomain ==<br />
<br />
= Disease and Therapeutics ==<br />
<br />
<scene name='10/1079536/Cpd6/1'>Cpd6 inhibitor</scene> <scene name='10/1079536/N514/1'>N514</scene> <scene name='10/1079536/2_bonds/1'>2 bonds</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Elizabeth Cook