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| <StructureSection load='6e6h' size='340' side='right'caption='[[6e6h]], [[Resolution|resolution]] 1.99Å' scene=''> | | <StructureSection load='6e6h' size='340' side='right'caption='[[6e6h]], [[Resolution|resolution]] 1.99Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6e6h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E6H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E6H FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6e6h]] 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=6E6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E6H FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.99Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6e6c|6e6c]], [[6e6p|6e6p]], [[6e6f|6e6f]], [[6e6g|6e6g]], [[6dzh|6dzh]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NRAS, HRAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6e6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e6h OCA], [https://pdbe.org/6e6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e6h RCSB], [https://www.ebi.ac.uk/pdbsum/6e6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e6h ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e6h OCA], [http://pdbe.org/6e6h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e6h RCSB], [http://www.ebi.ac.uk/pdbsum/6e6h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e6h ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/RASN_HUMAN RASN_HUMAN]] Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Defects in NRAS are the cause of Noonan syndrome type 6 (NS6) [MIM:[http://omim.org/entry/613224 613224]]. A syndrome characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:19966803</ref> Defects in NRAS are the cause of autoimmune lymphoproliferative syndrome type 4 (ALPS4) [MIM:[http://omim.org/entry/614470 614470]]. A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.<ref>PMID:17517660</ref> | | [https://www.uniprot.org/uniprot/RASN_HUMAN RASN_HUMAN] Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Defects in NRAS are the cause of Noonan syndrome type 6 (NS6) [MIM:[https://omim.org/entry/613224 613224]. A syndrome characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:19966803</ref> Defects in NRAS are the cause of autoimmune lymphoproliferative syndrome type 4 (ALPS4) [MIM:[https://omim.org/entry/614470 614470]. A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.<ref>PMID:17517660</ref> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/RASN_HUMAN RASN_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. | | [https://www.uniprot.org/uniprot/RASN_HUMAN RASN_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Ras GTPases are mutated at codons 12, 13, and 61, with different frequencies in KRas, HRas, and NRas and in a cancer-specific manner. The G13D mutant appears in 25% of KRas-driven colorectal cancers, while observed only rarely in HRas or NRas. Structures of Ras G13D in the three isoforms show an open active site, with adjustments to the D13 backbone torsion angles and with disconnected switch regions. KRas G13D has unique features that destabilize the nucleotide-binding pocket. In KRas G13D bound to GDP, A59 is placed in the Mg(2+) binding site, as in the HRas-SOS complex. Structure and biochemistry are consistent with an intermediate level of KRas G13D bound to GTP, relative to wild-type and KRas G12D, observed in genetically engineered mouse models. The results explain in part the elevated frequency of the G13D mutant in KRas over the other isoforms of Ras.
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| Isoform-Specific Destabilization of the Active Site Reveals a Molecular Mechanism of Intrinsic Activation of KRas G13D.,Johnson CW, Lin YJ, Reid D, Parker J, Pavlopoulos S, Dischinger P, Graveel C, Aguirre AJ, Steensma M, Haigis KM, Mattos C Cell Rep. 2019 Aug 6;28(6):1538-1550.e7. doi: 10.1016/j.celrep.2019.07.026. PMID:31390567<ref>PMID:31390567</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6e6h" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Johnson, C W]] | | [[Category: Johnson CW]] |
| [[Category: Mattos, C]] | | [[Category: Mattos C]] |
| [[Category: Oncogene]]
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| [[Category: P21]]
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| [[Category: Ra]]
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| [[Category: Signaling protein]]
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