Rho GTPase
From Proteopedia
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== Function == | == Function == | ||
| - | '''Rho GTPase''' of higher vertebrates include '''RhoA, RhoB''', '''RhoC''', '''RhoD''' and '''RhoE'''. These | + | '''Rho GTPase''' or '''Rho-related GTP-binding protein''' of higher vertebrates include '''RhoA, RhoB''', '''RhoC''', '''RhoD''' and '''RhoE'''. These proteins share 85% sequence identity. '''RhoA''' is the more extensively studied among these three. RhoA regulates a signal transduction phosphorylation pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Rho GTPase operates as a switch cycling between the active GTP-bound form and the inactive GDP-bound one. A number of proteins have been identified as targets of RhoA<ref>PMID:12642488</ref>. |
| + | *'''RhoB''' has a role in actin organisation, membrane trafficking, cell proliferation, DNA repair and apoptosis<ref>PMID:27875099</ref>. | ||
| + | *'''RhoD''' participates in regulating cell-cycle progression and centrosome duplication<ref>PMID:22665057</ref>. | ||
| + | *'''RhoE''' induces loss of stress fibres and inhibits cell cycle progression<ref>PMID:16042565</ref>. | ||
| + | *'''RhoG''' regulates actin-cytoskeleton dynamics, survival and proliferation in immune cells<ref>PMID:37378671</ref>. | ||
| + | * '''Mitochondrial Rho GTPase''' ('''Miro''') have tandem GTP-binding domains separated by a linker region containing calcium-binding EF hand motifs indicating a role in mitochondrial homeostasis and apoptosis<ref>PMID:12482879</ref>. | ||
| + | *'''Miro2''' regulates inter-mitochondrial communication along microtubules<ref>PMID:31455181</ref>. | ||
== Disease == | == Disease == | ||
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== Structural highlights == | == Structural highlights == | ||
| - | The <scene name='75/752220/Cv/ | + | The <scene name='75/752220/Cv/6'>transition state complex of RhoA and RhoGAP contains GDP, AlF4 and Mg+2 ion</scene><ref>PMID:9338791</ref>. Water molecules are shown as red spheres. |
| + | *<scene name='75/752220/Cv/7'>GDP binding site</scene> | ||
| + | *<scene name='75/752220/Cv/8'>AlF4 and Mg+2 ion binding site</scene>. | ||
| + | ==3D structures of Rho GTPase== | ||
| + | [[Rho GTPase 3D structures]] | ||
</StructureSection> | </StructureSection> | ||
| - | ==3D structures of Rho GTPase== | ||
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| - | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
| - | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
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| - | *RhoA | ||
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| - | **[[5ez6]], [[5c4m]], [[5a0f]], [[1dpf]], [[1ftn]] – hRhoA + GDP – human<br /> | ||
| - | **[[5a0f]] - hRhoA (mutant) + GDP<br /> | ||
| - | **[[1kmq]] – hRhoA (mutant) + GNP<br /> | ||
| - | **[[1a2b]] – hRhoA + GSP<br /> | ||
| - | **[[3tvd]] – mRhoA + GSP – mouse<br /> | ||
| - | |||
| - | *RhoA complex with guanine nucleotide exchange factor | ||
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| - | **[[4xh9]] – hRhoA (mutant) + guanine nucleotide exchange factor NET1<br /> | ||
| - | **[[5jhg]], [[5jhh]] - hRhoA + guanine nucleotide exchange factor 11<br /> | ||
| - | **[[3t06]], [[1xcg]] – hRhoA (mutant) + guanine nucleotide exchange factor 11<br /> | ||
| - | **[[1lb1]] – hRhoA (mutant) + guanine nucleotide exchange factor Dbs<br /> | ||
| - | **[[3kz1]] – hRhoA + guanine nucleotide exchange factor 11 + GSP<br /> | ||
| - | **[[1x86]] – hRhoA + guanine nucleotide exchange factor 12<br /> | ||
| - | **[[6bcb]] – hRhoA + guanine nucleotide exchange factor 18<br /> | ||
| - | **[[6bc0]] – hRhoA + guanine nucleotide exchange factor 28 + GTP analog<br /> | ||
| - | |||
| - | *RhoA complex with Rho GTPase-activating protein | ||
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| - | **[[5irc]] – hRhoA + Rho GTPase-activating protein 20 + GDP <br /> | ||
| - | **[[1ow3]], [[5m6x]], [[5m70]] – hRhoA + Rho GTPase-activating protein 1 + GDP <br /> | ||
| - | **[[3msx]] – hRhoA (mutant) + Rho GTPase-activating protein 35 + GDP <br /> | ||
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| - | *RhoA complex with ADP-ribosyltransferase | ||
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| - | **[[4xsg]] – hRhoA (mutant) + ADP-ribosyltransferase + GTP <br /> | ||
| - | **[[4xsh]] – hRhoA (mutant) + ADP-ribosyltransferase + GSP + NADH<br /> | ||
| - | **[[5bwm]] – hRhoA (mutant) + ADP-ribosyltransferase + GDP + NADH<br /> | ||
| - | |||
| - | *RhoA other complexes | ||
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| - | **[[5fr2]], [[5fr1]], [[1cc0]] – hRhoA + Rho GDP-dissociation inhibitor 1 + GDP <br /> | ||
| - | **[[5hpy]] – hRhoA (mutant) + unconventional myosin-IXB + GDP <br /> | ||
| - | **[[4xoi]] – hRhoA (mutant) + actin-binding protein anillin + GTP <br /> | ||
| - | **[[4f38]] – mRhoA + Rho GDP-dissociation inhibitor 1 + GPPNP <br /> | ||
| - | **[[4d0n]], [[6bca]] – hRhoA + A-kinase anchor protein 13 + GDP<br /> | ||
| - | **[[3lw8]], [[3lwn]], [[3lxr]] – hRhoA + IpgB2 + GDP<br /> | ||
| - | **[[1s1c]] – hRhoA + ROCKI + GNP<br /> | ||
| - | **[[1cxz]] – hRhoA + Pkn/Prk1 + GSP<br /> | ||
| - | **[[1tx4]] – hRhoA + RhoGap + GDP<br /> | ||
| - | **[[2rgn]] – hRhoA + guanine nucleotide-binding protein alpha-Q + RhoA/Rac/CDC42 exchange factor + GDP<br /> | ||
| - | **[[5c2k]] – hRhoA/Rac GTPase-activating protein 1 + GDP <br /> | ||
| - | **[[5jcp]] – hRhoA/ARAP3 + GDP <br /> | ||
| - | **[[5zhx]] – hRhoA (mutant) + RAP1 <br /> | ||
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| - | *RhoB | ||
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| - | **[[2fv8]] – hRhoB + GDP <br /> | ||
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| - | *RhoC | ||
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| - | **[[2gcn]] – hRhoC + GDP <br /> | ||
| - | **[[2gco]] – hRhoC + GPPNP <br /> | ||
| - | **[[2gcp]] – hRhoC + GSP <br /> | ||
| - | **[[2gcn]] – hRhoC (mutant) + diaphanous protein homolog 1 + GMPPNP <br /> | ||
| - | |||
| - | *RhoD | ||
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| - | **[[2j1l]] – hRhoD + GDP <br /> | ||
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| - | *RhoE | ||
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| - | **[[1m7b]] – hRhoE + GTP <br /> | ||
| - | **[[1gwn]] – mRhoE core domain + GTP <br /> | ||
| - | **[[2v55]] – hRhoE + ROCKI + GTP + ANP<br /> | ||
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| - | *Miro1 | ||
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| - | **[[5kso]], [[5ksp]], [[5ksy]] – hMiro1 C-terminal + GDP <br /> | ||
| - | **[[5ksz]] – hMiro1 EF hand and kinase domain + GMPPCP <br /> | ||
| - | **[[5kty]], [[5ku1]] – hMiro1 EF hand and kinase domain + GDP <br /> | ||
| - | |||
| - | *Miro2 | ||
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| - | **[[5kut]] – hMiro2 C-terminal + GDP <br /> | ||
| - | |||
| - | *Miro | ||
| - | |||
| - | **[[4c0j]], [[4c0k]] – DmMiro – ''Drosophila melanogaster'' <br /> | ||
| - | **[[4c0l]] – DmMiro + GDP <br /> | ||
| - | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Current revision
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References
- ↑ Sepp KJ, Auld VJ. RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Development. 2003 May;130(9):1825-35. PMID:12642488
- ↑ Vega FM, Ridley AJ. The RhoB small GTPase in physiology and disease. Small GTPases. 2018 Sep 3;9(5):384-393. PMID:27875099 doi:10.1080/21541248.2016.1253528
- ↑ Kyrkou A, Soufi M, Bahtz R, Ferguson C, Bai M, Parton RG, Hoffmann I, Zerial M, Fotsis T, Murphy C. RhoD participates in the regulation of cell-cycle progression and centrosome duplication. Oncogene. 2013 Apr 4;32(14):1831-42. PMID:22665057 doi:10.1038/onc.2012.195
- ↑ Riento K, Villalonga P, Garg R, Ridley A. Function and regulation of RhoE. Biochem Soc Trans. 2005 Aug;33(Pt 4):649-51. PMID:16042565 doi:10.1042/BST0330649
- ↑ Rai SK, Singh D, Sarangi PP. Role of RhoG as a regulator of cellular functions: integrating insights on immune cell activation, migration, and functions. Inflamm Res. 2023 Jul;72(7):1453-1463. PMID:37378671 doi:10.1007/s00011-023-01761-9
- ↑ Fransson A, Ruusala A, Aspenstrom P. Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem. 2003 Feb 21;278(8):6495-502. Epub 2002 Dec 12. PMID:12482879 doi:http://dx.doi.org/10.1074/jbc.M208609200
- ↑ Cao Y, Xu C, Ye J, He Q, Zhang X, Jia S, Qiao X, Zhang C, Liu R, Weng L, Liu Y, Liu L, Zheng M. Miro2 Regulates Inter-Mitochondrial Communication in the Heart and Protects Against TAC-Induced Cardiac Dysfunction. Circ Res. 2019 Sep 27;125(8):728-743. PMID:31455181 doi:10.1161/CIRCRESAHA.119.315432
- ↑ Zhou J, Hayakawa Y, Wang TC, Bass AJ. RhoA mutations identified in diffuse gastric cancer. Cancer Cell. 2014 Jul 14;26(1):9-11. doi: 10.1016/j.ccr.2014.06.022. PMID:25026207 doi:http://dx.doi.org/10.1016/j.ccr.2014.06.022
- ↑ Jin L, Burnett AL. RhoA/Rho-kinase in erectile tissue: mechanisms of disease and therapeutic insights. Clin Sci (Lond). 2006 Feb;110(2):153-65. PMID:16411892 doi:http://dx.doi.org/10.1042/CS20050255
- ↑ Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ. Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue. Nature. 1997 Oct 16;389(6652):758-62. PMID:9338791 doi:10.1038/39651
