5yde

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<StructureSection load='5yde' size='340' side='right'caption='[[5yde]], [[Resolution|resolution]] 1.02&Aring;' scene=''>
<StructureSection load='5yde' size='340' side='right'caption='[[5yde]], [[Resolution|resolution]] 1.02&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5yde]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YDE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5YDE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5yde]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YDE FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5yde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yde OCA], [http://pdbe.org/5yde PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yde RCSB], [http://www.ebi.ac.uk/pdbsum/5yde PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yde ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.023&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5yde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yde OCA], [https://pdbe.org/5yde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yde RCSB], [https://www.ebi.ac.uk/pdbsum/5yde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yde ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/CDC73_HUMAN CDC73_HUMAN]] Familial isolated hyperparathyroidism;Parathyroid carcinoma;Hyperparathyroidism-jaw tumor syndrome;Familial parathyroid adenoma. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry is involved in disease pathogenesis.
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[https://www.uniprot.org/uniprot/CDC73_HUMAN CDC73_HUMAN] Familial isolated hyperparathyroidism;Parathyroid carcinoma;Hyperparathyroidism-jaw tumor syndrome;Familial parathyroid adenoma. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry is involved in disease pathogenesis.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/CDC73_HUMAN CDC73_HUMAN]] Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors.<ref>PMID:15580289</ref> <ref>PMID:15632063</ref> <ref>PMID:15923622</ref> <ref>PMID:16630820</ref> <ref>PMID:16989776</ref> <ref>PMID:19136632</ref> <ref>PMID:19952111</ref> <ref>PMID:20178742</ref> <ref>PMID:20541477</ref> <ref>PMID:21329879</ref>
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[https://www.uniprot.org/uniprot/CDC73_HUMAN CDC73_HUMAN] Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors.<ref>PMID:15580289</ref> <ref>PMID:15632063</ref> <ref>PMID:15923622</ref> <ref>PMID:16630820</ref> <ref>PMID:16989776</ref> <ref>PMID:19136632</ref> <ref>PMID:19952111</ref> <ref>PMID:20178742</ref> <ref>PMID:20541477</ref> <ref>PMID:21329879</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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CDC73/Parafibromin is a critical component of the Paf1 complex (PAF1C), which is involved in transcriptional elongation and histone modifications. Mutations of the human CDC73/HRPT2 gene are associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disorder. CDC73/parafibromin was initially recognized as a tumor suppressor by inhibiting cell proliferation via repression of cyclin D1 and c-myc genes. In recent years, it has also shown oncogenic features by activating the canonical Wnt/beta-catenin signal pathway. Here, through limited proteolysis analysis, we demonstrate that the evolutionarily conserved human CDC73 N-terminal 111 residues form a globularly folded domain (hCDC73-NTD). We have determined a crystal structure of hCDC73-NTD at 1.02 A resolution, which reveals a novel protein fold. CDC73-NTD contains an extended hydrophobic groove on its surface that may be important for its function. Most pathogenic CDC73 missense mutations associated with the HPT-JT syndrome are located in the region encoding CDC73-NTD. Our crystal and biochemical data indicate that most CDC73 missense mutations disrupt the folding of the hydrophobic core of hCDC73-NTD, while others such as the K34Q mutant reduce its thermostability. Overall, our results provide a solid structural basis for understanding the structure and function of CDC73 and its association with the HPT-JT syndrome and other diseases.
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Crystal structure of the N-terminal domain of human CDC73 and its implications for the hyperparathyroidism-jaw tumor (HPT-JT) syndrome.,Sun W, Kuang XL, Liu YP, Tian LF, Yan XX, Xu W Sci Rep. 2017 Nov 15;7(1):15638. doi: 10.1038/s41598-017-15715-9. PMID:29142233<ref>PMID:29142233</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5yde" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Kuang, X L]]
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[[Category: Kuang XL]]
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[[Category: Liu, Y P]]
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[[Category: Liu YP]]
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[[Category: Sun, W]]
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[[Category: Sun W]]
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[[Category: Tian, L F]]
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[[Category: Tian LF]]
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[[Category: Xu, W Q]]
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[[Category: Xu WQ]]
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[[Category: Yan, X X]]
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[[Category: Yan XX]]
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[[Category: Cancer]]
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[[Category: Transcription]]
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[[Category: Tumor suppressor]]
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Current revision

Crystal structure of a disease-related gene, hCDC73(1-111)

PDB ID 5yde

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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