5grq: Difference between revisions

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<StructureSection load='5grq' size='340' side='right'caption='[[5grq]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
<StructureSection load='5grq' size='340' side='right'caption='[[5grq]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5grq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GRQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GRQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[5grq]] is a 4 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=5GRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GRQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.584&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5grq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5grq OCA], [http://pdbe.org/5grq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5grq RCSB], [http://www.ebi.ac.uk/pdbsum/5grq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5grq ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5grq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5grq OCA], [https://pdbe.org/5grq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5grq RCSB], [https://www.ebi.ac.uk/pdbsum/5grq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5grq ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ATRX_HUMAN ATRX_HUMAN]] Defects in ATRX are the cause of alpha-thalassemia mental retardation syndrome X-linked (ATRX) [MIM:[http://omim.org/entry/301040 301040]]. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.<ref>PMID:8968741</ref> <ref>PMID:7697714</ref> <ref>PMID:9043863</ref> <ref>PMID:9326931</ref> <ref>PMID:10660327</ref> <ref>PMID:10417298</ref> <ref>PMID:10204841</ref> <ref>PMID:10995512</ref> <ref>PMID:12116232</ref> <ref>PMID:16955409</ref>  Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:[http://omim.org/entry/309580 309580]]; also called Carpenter-Waziri syndrome (CWS), Juberg-Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.<ref>PMID:10751095</ref> <ref>PMID:8630485</ref> <ref>PMID:10398237</ref> <ref>PMID:11050622</ref> <ref>PMID:16222662</ref> <ref>PMID:15565397</ref>  Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:[http://omim.org/entry/300448 300448]]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.<ref>PMID:12858175</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/DAXX_HUMAN DAXX_HUMAN]] Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively.<ref>PMID:12140263</ref> <ref>PMID:15364927</ref> <ref>PMID:17081986</ref> <ref>PMID:16845383</ref> [[http://www.uniprot.org/uniprot/ATRX_HUMAN ATRX_HUMAN]] Could be a global transcriptional regulator. Modifies gene expression by affecting chromatin. May be involved in brain development and facial morphogenesis.
[https://www.uniprot.org/uniprot/DAXX_HUMAN DAXX_HUMAN] Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively.<ref>PMID:12140263</ref> <ref>PMID:15364927</ref> <ref>PMID:17081986</ref> <ref>PMID:16845383</ref>  


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: DNA helicase]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Li, H]]
[[Category: Li H]]
[[Category: Helical bundle protein]]
[[Category: Hydrolase]]

Latest revision as of 14:40, 2 August 2023

Crystal Structure of DHB domain of Daxx in complex with an ATRX peptideCrystal Structure of DHB domain of Daxx in complex with an ATRX peptide

Structural highlights

5grq is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.584Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DAXX_HUMAN Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively.[1] [2] [3] [4]

See Also

References

  1. ↑ Hollenbach AD, McPherson CJ, Mientjes EJ, Iyengar R, Grosveld G. Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci. 2002 Aug 15;115(Pt 16):3319-30. PMID:12140263
  2. ↑ Zhao LY, Liu J, Sidhu GS, Niu Y, Liu Y, Wang R, Liao D. Negative regulation of p53 functions by Daxx and the involvement of MDM2. J Biol Chem. 2004 Nov 26;279(48):50566-79. Epub 2004 Sep 10. PMID:15364927 doi:10.1074/jbc.M406743200
  3. ↑ Lin DY, Huang YS, Jeng JC, Kuo HY, Chang CC, Chao TT, Ho CC, Chen YC, Lin TP, Fang HI, Hung CC, Suen CS, Hwang MJ, Chang KS, Maul GG, Shih HM. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell. 2006 Nov 3;24(3):341-54. PMID:17081986 doi:10.1016/j.molcel.2006.10.019
  4. ↑ Tang J, Qu LK, Zhang J, Wang W, Michaelson JS, Degenhardt YY, El-Deiry WS, Yang X. Critical role for Daxx in regulating Mdm2. Nat Cell Biol. 2006 Aug;8(8):855-62. Epub 2006 Jul 16. PMID:16845383 doi:10.1038/ncb1442

5grq, resolution 1.58Å

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