View source for 1bor


==TRANSCRIPTION FACTOR PML, A PROTO-ONCOPROTEIN, NMR, 1 REPRESENTATIVE STRUCTURE AT PH 7.5, 30 C, IN THE PRESENCE OF ZINC==
<StructureSection load='1bor' size='340' side='right'caption='[[1bor]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1bor]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BOR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BOR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=1bor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bor OCA], [https://pdbe.org/1bor PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bor RCSB], [https://www.ebi.ac.uk/pdbsum/1bor PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bor ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PML_HUMAN PML_HUMAN] Note=A chromosomal aberration involving PML may be a cause of acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) with RARA. The PML breakpoints (type A and type B) lie on either side of an alternatively spliced exon.<ref>PMID:1652369</ref> <ref>PMID:1720570</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PML_HUMAN PML_HUMAN] Key component of PML nuclear bodies that regulate a large number of cellular processes by facilitating post-translational modification of target proteins, promoting protein-protein contacts, or by sequestering proteins. Functions as tumor suppressor. Required for normal, caspase-dependent apoptosis in response to DNA damage, FAS, TNF, or interferons. Plays a role in transcription regulation, DNA damage response, DNA repair and chromatin organization. Plays a role in processes regulated by retinoic acid, regulation of cell division, terminal differentiation of myeloid precursor cells and differentiation of neural progenitor cells. Required for normal immunity to microbial infections. Plays a role in antiviral response. In the cytoplasm, plays a role in TGFB1-dependent processes. Regulates p53/TP53 levels by inhibiting its ubiquitination and proteasomal degradation. Regulates activation of p53/TP53 via phosphorylation at 'Ser-20'. Sequesters MDM2 in the nucleolus after DNA damage, and thereby inhibits ubiquitination and degradation of p53/TP53. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates RB1 phosphorylation and activity. Required for normal development of the brain cortex during embryogenesis. Can sequester herpes virus and varicella virus proteins inside PML bodies, and thereby inhibit the formation of infectious viral particles. Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum (By similarity). Regulates transcription activity of ELF4. Inhibits specifically the activity of the tetrameric form of PKM. Together with SATB1, involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Regulates PTEN compartmentalization through the inhibition of USP7-mediated deubiquitination.<ref>PMID:9756909</ref> <ref>PMID:10610177</ref> <ref>PMID:10684855</ref> <ref>PMID:11025664</ref> <ref>PMID:11432836</ref> <ref>PMID:12402044</ref> <ref>PMID:12439746</ref> <ref>PMID:12810724</ref> <ref>PMID:14976184</ref> <ref>PMID:15195100</ref> <ref>PMID:15356634</ref> <ref>PMID:17030982</ref> <ref>PMID:18298799</ref> <ref>PMID:18716620</ref> <ref>PMID:17173041</ref> <ref>PMID:19567472</ref> <ref>PMID:21172801</ref> <ref>PMID:21304940</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bo/1bor_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bor ConSurf].
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== Publication Abstract from PubMed ==
Acute promyelocytic leukaemia (APL) has been ascribed to a chromosomal translocation event which results in a fusion protein comprising the PML protein and the retinoic acid receptor alpha. PML is normally a component of a nuclear multiprotein complex (termed ND10, Kr bodies, nuclear bodies, PML oncogenic domains or PODs) which is disrupted in the APL disease state. PML contains a number of characterized motifs including a Zn2+ binding domain called the RING or C3HC4 finger. Here we describe the solution structure of the PML RING finger as solved by 1H NMR methods at physiological pH with r.m.s. deviations for backbone atoms of 0.88 and 1.39 A for all atoms. Additional biophysical studies including CD and optical spectroscopy, show that the PML RING finger requires Zn2+ for autonomous folding and that cysteines are used in metal ligation. A comparison of the structure with the previously solved equine herpes virus IE110 RING finger, shows significant differences suggesting that the RING motif is structurally diverse. The role of the RING domain in PML nuclear body formation was tested in vivo, by using site-directed mutagenesis and immunofluorescence on transiently transfected NIH 3T3 cells. Independently mutating two pairs of cysteines in each of the Zn2+ binding sites prevents PML nuclear body formation, suggesting that a fully folded RING domain is necessary for this process. These results suggest that the PML RING domain is probably involved in protein-protein interactions, a feature which may be common to other RING finger domains.

The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML.,Borden KL, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS EMBO J. 1995 Apr 3;14(7):1532-41. PMID:7729428<ref>PMID:7729428</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Borden KLB]]
[[Category: Freemont PS]]