Peregrin: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman, Brian Boyle

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 == '''Overview''' ==
-'''Peregrin''', also known as Bromodomain and PHD Finger-containing 1 ('''BRPF1''') is a 137 kDa protein that plays a versatile role in epigenetic signaling events. It contains three chromatin reader domains, including a <scene name='91/910741/Apo_bromodomain/1'>bromodomain</scene>, <scene name='91/910741/Apo_pzp/1'>PZP domain</scene> (two PHD fingers separated by a Zinc Knuckle), and '''proline-tryptophan-tryptophan-proline (<scene name='91/910741/Pwwp_unliganded/1'>PWWP</scene>) domain''' (from N to C terminus)<ref name="Yan">PMID:27939640</ref>. Through these three domains, it is capable of recognizing both modified and unmodified histones, as well as non-specifically binding DNA <ref name="Klein">PMID:31711755</ref>,<ref name="Glass1">PMID:24333487</ref>. BRPF1 carries out its function as a component of the MOZ (monocytic leukemic zinc-finger protein) histone acetyltransferase (HAT) complex <ref name="Obi">PMID:33554132</ref>. This complex is involved in the regulation of gene expression, particularly those involved with skeletal development, hematopoiesis, and neurodevelopmental processes <ref>PMID:19254709</ref>,<ref>PMID:27500495</ref>,<ref name="Klein" />. Accordingly, it has the greatest tissue distribution in the bone marrow and brain.
+'''Peregrin''', also known as '''Bromodomain and PHD Finger-containing 1''' ('''BRPF1''') is a 137 kDa protein that plays a versatile role in epigenetic signaling events. It contains three chromatin reader domains, including a <scene name='91/910741/Apo_bromodomain/1'>bromodomain</scene>, <scene name='91/910741/Apo_pzp/1'>PZP domain</scene> (two PHD fingers separated by a Zinc Knuckle), and '''proline-tryptophan-tryptophan-proline (<scene name='91/910741/Pwwp_unliganded/1'>PWWP</scene>) domain''' (from N to C terminus)<ref name="Yan">PMID:27939640</ref>. Through these three domains, it is capable of recognizing both modified and unmodified histones, as well as non-specifically binding DNA <ref name="Klein">PMID:31711755</ref>,<ref name="Glass1">PMID:24333487</ref>. BRPF1 carries out its function as a component of the MOZ (monocytic leukemic zinc-finger protein) histone acetyltransferase (HAT) complex <ref name="Obi">PMID:33554132</ref>. This complex is involved in the regulation of gene expression, particularly those involved with skeletal development, hematopoiesis, and neurodevelopmental processes <ref>PMID:19254709</ref>,<ref>PMID:27500495</ref>,<ref name="Klein" />. Accordingly, it has the greatest tissue distribution in the bone marrow and brain.
 == '''PZP Domain''' ==
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 == '''PWWP Domain''' ==
-PWWP domains are a weakly conserved protein module that often contain a proline-tryptophan-tryptophan-proline motif and have been show to recognize methylated histones<ref name="chen">PMID:11836534</ref>. The BRPF1 PWWP domain has high selectivity for histone H3 Lys-36 ([[2x4w]]) that has been trimethylated (H3K36me3)<ref name="Vezzoli">PMID:20400950</ref>. The trimethyl mark at H3K36 has gained a lot attention due to its established roles is RNA splicing and developmental disorders<ref name="Paulina">PMID:19182803</ref>,<ref name="Nimura">PMID:19483677</ref>. Recognition of H3K36me3 is strongly dependent on the <scene name='91/910741/Pwwp_aromatic_cage/1'>aromatic cage</scene>, which consists of Tyr-1096, Tyr-1099, and Phe-1147.
+PWWP domains are a weakly conserved protein module that often contain a proline-tryptophan-tryptophan-proline motif and have been show to recognize methylated histones<ref name="chen">PMID:11836534</ref>. The BRPF1 PWWP domain has high selectivity for histone H3 Lys-36 ([[2x4w]]) that has been trimethylated (H3K36me3)<ref name="Vezzoli">PMID:20400950</ref>. The trimethyl mark at H3K36 has gained a lot attention due to its established roles is RNA splicing and developmental disorders<ref name="Paulina">PMID:19182803</ref>,<ref name="Nimura">PMID:19483677</ref>. Recognition of H3K36me3 is strongly dependent on the <scene name='91/910741/Pwwp_aromatic_cage/1'>aromatic cage</scene>, which consists of Tyr-1096, Tyr-1099, and Phe-1147. Mutations of any of these aromatic residues abolishes all binding to the histone peptide<ref name="Vezzoli" />.
 </StructureSection>
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 Mutations within the gene itself have been associated with neurological disorders and widespread reduced histone acetylation <ref name="Yan" />.
-== '''Available Structures''' ==
+==Peregrin PDB structures==
-The following are some, but not all, of the available structures containing domains of BRPF1:
-Bromodomain (apo): [[2d92]]
+Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-Bromodomain w/ histone peptides: [[4qyl]], [[4qyd]], [[5ffv]], [[5ffw]]
+{{#tree:id=OrganizedByTopic|openlevels=0|
-Bromodomain w/ inhibitors: [[6ekq]], [[5ov8]], [[5o5h]], [[5o5f]], [[5o5a]], [[5o55]]
-PZP (apo): [[5erc]]
+* Peregrin; Domains – PZP 274-450; bromodomain 626-740; PWWP 1079-1207
-PZP w/ histone H3 peptide: [[6u04]]
-PWWP (apo): [[2x35]]
+**[[3l42]] – hBRPF1 PWWP domain - human<br />
-PWWP w/ H3K36me3: [[2x4w]], [[2x4y]], [[2x4x]]
+**[[5erc]] – hBRPF1 PZP domain<br />
+**[[4lc2]], [[7c4i]]  – hBRPF1 bromodomain <br />
+**[[2d9e]]  – hBRPF1 bromodomain - NMR<br />
+* Peregrin complexes
+**[[5ewv]], [[5eww]], [[5c89]], [[5g4r]], [[5g4s]], [[5em3]], [[5ev9]], [[5eva]], [[5ewh]], [[5c85]], [[5c87]], [[5d7x]], [[5dy7]], [[5d7a]], [[5dyc]], [[5e3d]], [[5e3g]], [[5epr]], [[5eps]], [[5eq1]], [[5etb]], [[5etd]], [[5ewc]], [[5ewd]], [[5ffy]], [[5c7n]], [[4uye]], [[5dya]]  – hBRPF1 bromodomain + ligand <br />
+**[[5ffv]], [[5ffw]], [[4qyd]], [[4qyl]]  – hBRPF1 bromodomain + histone peptide<br />
+**[[2rs9]]  – hBRPF1 bromodomain + histone peptide - NMR<br />
+**[[3mo8]], [[2x4w]], [[2x4x]], [[2x4y]], [[2x35]]  – hBRPF1 PWWP domain + histone peptide<br />
+**[[5fg5]], [[5fg4]], [[5myg]]  – hBRPF1 bromodomain + chemical probe<br />
+**[[5t4u]], [[5t4v]], [[5mwg]], [[5mwh]], [[5mwz]], [[5o4s]], [[5o4t]], [[5o55]], [[5o5a]], [[5o5f]], [[5o5h]], [[5ov8]], [[5owa]], [[5owb]], [[5owe]], [[6ekq]] – hBRPF1 bromodomain + inhibitor<br />
+**[[5c6s]]  – hBRPF1 PWWP domain + ligand <br />
+}}
 == '''References''' ==
 <references/>
+[[Category:Topic Page]]