9btm: Difference between revisions

Latest revision as of 09:11, 2 April 2025

NRas 1-169 Q61R in Complex with Shoc2 80-582

Structural highlights

9btm is a 2 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 2.73Å
Ligands:	GTP, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SHOC2_HUMAN Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.

Function

SHOC2_HUMAN Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway (PubMed:10783161, PubMed:16630891, PubMed:25137548, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Acts as a scaffolding protein in the SMP complex (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:10783161, PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Li W, Han M, Guan KL. The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf. Genes Dev. 2000 Apr 15;14(8):895-900. PMID:10783161
↑ Rodriguez-Viciana P, Oses-Prieto J, Burlingame A, Fried M, McCormick F. A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity. Mol Cell. 2006 Apr 21;22(2):217-30. doi: 10.1016/j.molcel.2006.03.027. PMID:16630891 doi:https://dx.doi.org/10.1016/j.molcel.2006.03.027
↑ Hannig V, Jeoung M, Jang ER, Phillips JA 3rd, Galperin E. A Novel SHOC2 Variant in Rasopathy. Hum Mutat. 2014 Nov;35(11):1290-4. doi: 10.1002/humu.22634. Epub 2014 Sep 11. PMID:25137548 doi:https://dx.doi.org/10.1002/humu.22634
↑ Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Structural basis for SHOC2 modulation of RAS signalling. Nature. 2022 Jun 29. pii: 10.1038/s41586-022-04838-3. doi:, 10.1038/s41586-022-04838-3. PMID:35768504 doi:https://dx.doi.org/10.1038/s41586-022-04838-3
↑ Hauseman ZJ, Fodor M, Dhembi A, Viscomi J, Egli D, Bleu M, Katz S, Park E, Jang DM, Porter KA, Meili F, Guo H, Kerr G, Molle S, Velez-Vega C, Beyer KS, Galli GG, Maira SM, Stams T, Clark K, Eck MJ, Tordella L, Thoma CR, King DA. Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature. 2022 Jul 13. pii: 10.1038/s41586-022-05086-1. doi:, 10.1038/s41586-022-05086-1. PMID:35830882 doi:https://dx.doi.org/10.1038/s41586-022-05086-1
↑ Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ. Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. Nature. 2022 Jul 13. pii: 10.1038/s41586-022-04928-2. doi:, 10.1038/s41586-022-04928-2. PMID:35831509 doi:https://dx.doi.org/10.1038/s41586-022-04928-2
↑ Bonsor DA, Alexander P, Snead K, Hartig N, Drew M, Messing S, Finci LI, Nissley DV, McCormick F, Esposito D, Rodriguez-Viciana P, Stephen AG, Simanshu DK. Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome. Nat Struct Mol Biol. 2022 Oct;29(10):966-977. PMID:36175670 doi:10.1038/s41594-022-00841-4

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Li W, Han M, Guan KL. The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf. Genes Dev. 2000 Apr 15;14(8):895-900. PMID:10783161

[2] Rodriguez-Viciana P, Oses-Prieto J, Burlingame A, Fried M, McCormick F. A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity. Mol Cell. 2006 Apr 21;22(2):217-30. doi: 10.1016/j.molcel.2006.03.027. PMID:16630891 doi:https://dx.doi.org/10.1016/j.molcel.2006.03.027

[3] Hannig V, Jeoung M, Jang ER, Phillips JA 3rd, Galperin E. A Novel SHOC2 Variant in Rasopathy. Hum Mutat. 2014 Nov;35(11):1290-4. doi: 10.1002/humu.22634. Epub 2014 Sep 11. PMID:25137548 doi:https://dx.doi.org/10.1002/humu.22634

[4] Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Structural basis for SHOC2 modulation of RAS signalling. Nature. 2022 Jun 29. pii: 10.1038/s41586-022-04838-3. doi:, 10.1038/s41586-022-04838-3. PMID:35768504 doi:https://dx.doi.org/10.1038/s41586-022-04838-3

[5] Hauseman ZJ, Fodor M, Dhembi A, Viscomi J, Egli D, Bleu M, Katz S, Park E, Jang DM, Porter KA, Meili F, Guo H, Kerr G, Molle S, Velez-Vega C, Beyer KS, Galli GG, Maira SM, Stams T, Clark K, Eck MJ, Tordella L, Thoma CR, King DA. Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature. 2022 Jul 13. pii: 10.1038/s41586-022-05086-1. doi:, 10.1038/s41586-022-05086-1. PMID:35830882 doi:https://dx.doi.org/10.1038/s41586-022-05086-1

[6] Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ. Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. Nature. 2022 Jul 13. pii: 10.1038/s41586-022-04928-2. doi:, 10.1038/s41586-022-04928-2. PMID:35831509 doi:https://dx.doi.org/10.1038/s41586-022-04928-2

[7] Bonsor DA, Alexander P, Snead K, Hartig N, Drew M, Messing S, Finci LI, Nissley DV, McCormick F, Esposito D, Rodriguez-Viciana P, Stephen AG, Simanshu DK. Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome. Nat Struct Mol Biol. 2022 Oct;29(10):966-977. PMID:36175670 doi:10.1038/s41594-022-00841-4

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9btm is ON HOLD
+==NRas 1-169 Q61R in Complex with Shoc2 80-582==
+<StructureSection load='9btm' size='340' side='right'caption='[[9btm]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9btm]] is a 2 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=9BTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BTM FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.73&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9btm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9btm OCA], [https://pdbe.org/9btm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9btm RCSB], [https://www.ebi.ac.uk/pdbsum/9btm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9btm ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN] Noonan syndrome-like disorder with loose anagen hair. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/SHOC2_HUMAN SHOC2_HUMAN] Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway (PubMed:10783161, PubMed:16630891, PubMed:25137548, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Acts as a scaffolding protein in the SMP complex (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:10783161, PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670).<ref>PMID:10783161</ref> <ref>PMID:16630891</ref> <ref>PMID:25137548</ref> <ref>PMID:35768504</ref> <ref>PMID:35830882</ref> <ref>PMID:35831509</ref> <ref>PMID:36175670</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Fodor M]]
+[[Category: Hauseman ZJ]]
+[[Category: King D]]
+[[Category: Viscomi J]]

9btm: Difference between revisions

Latest revision as of 09:11, 2 April 2025

NRas 1-169 Q61R in Complex with Shoc2 80-582

Structural highlights

Disease

Function

References

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