Rho GTPase activating protein: Difference between revisions

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<StructureSection load='1ow3' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load='' size='350' side='right' caption='Human RhoGAP 1 (magenta) complex with RhoA (blue), GDP, MgF3 and Mg+2 ions (PDB code [[1ow3]])' scene='75/750307/Cv1/1' pspeed='8'>
 
__TOC__
== Function ==
== Function ==
'''Rho GTPase acivating protein''' (RhoGAP) are one of the main classes of Rho GTPase regulators that are crucial in cell cytoskeletal organization, growth, differentiation, neuronal development and synaptic functions<ref>PMID:12480336</ref>.  RhoGAPs contain a RhoGAP domain.
'''Rho GTPase activating protein''' (RhoGAP) are one of the main classes of Rho GTPase regulators that are crucial in cell cytoskeletal organization, growth, differentiation, neuronal development and synaptic functions<ref>PMID:12480336</ref>,<ref>PMID:17222083</ref>.  RhoGAPs contain a RhoGAP domain.
*'''RhoGAP7''' activates the small GTPases RHOA, RHOB, RHOC and CDC42.
*'''RhoGAP9''' regulates adhesion of hematopoietic cells to the extracellular matrix.
*'''RhoGAP11''' causes cell-cycle arrest and apoptosis in response to DNA damage.
*'''RhoGAP12''' may be involved in suppressing tumor formation.
*'''RhoGAP21''' involved in cell adhesion, migration, Golgi regulation, cell trafficking and insulin secretion<ref>PMID:29856495</ref>.
*'''RhoGAP21''' involved in cell adhesion, migration, Golgi regulation, cell trafficking and insulin secretion<ref>PMID:29856495</ref>.
*'''RhoGAP35''' involved in cell adhesion, migration and invasion<ref>PMID:35758029</ref>.


== Relevance ==
== Relevance ==
RhoGAPs are present in altered abundance in a variety of human cancers and may serve as targets for cancer therapy<ref>PMID:16918449</ref>.
RhoGAPs are present in altered abundance in a variety of human cancers and may serve as targets for cancer therapy<ref>PMID:16918449</ref>,<ref>PMID:34365932</ref>.  RhoGAP10 variants may be associated with schizophrenia<ref>PMID:32699248</ref>.


== Structural highlights ==
== Structural highlights ==
The <scene name='75/750307/Cv/6'>active site of RhoGAP</scene> contains a <scene name='75/750307/Cv/7'>catalytic arginine</scene> and GDP<ref>PMID:11927263</ref>. Water molecules are shown as red spheres. <scene name='75/750307/Cv/8'>Mg/MgF3 coordination site</scene>.


 
==3D structures of Rho GTPase activating protein==
[[Rho GTPase activating protein 3D structures]]


</StructureSection>
</StructureSection>
==3D structures of Rho GTPase activating protein==
[[4u3k]] - yRhoGAP 1 RhoGAP domain - yeast<br />
[[1ow3]] - hRhoGAP 1 residues 198-439 + RhoA + GDP - human<br />
[[5irc]] - RhoGAP 35 + RhoA - rat<br />
[[4rtt]], [[4rug]], [[2gnc]] - hRhoGAP 2 SLIT-ROBO SH3 domain <br />
[[2dl8]] - hRhoGAP 2 SLIT-ROBO SH3 domain - NMR<br />
[[2epd]] - hRhoGAP 4 SH3 domain - NMR<br />
[[2ee4]] , [[2ee5]] - hRhoGAP 5 (mutant) RhoGAP domain - NMR<br />
[[3kuq]] - hRhoGAP 7 RhoGAP domain<br />
[[2kap]], [[2dky]] - hRhoGAP 7 SAM domain - NMR<br />
[[2p0d]], [[2p0f]], [[2p0h]] - hRhoGAP 9 pleckstrin homology domain + phosphoinositide<br />
[[2mio]] - hRhoGAP 10 SH3 domain - NMR<br />
[[2j59]] - hRhoGAP 10 ARF-binding domain + ADP-ribosylation factor<br />
[[3eap]] - hRhoGAP 11A RhoGAP domain<br />
[[3byi]] - RhoGAP 15 residues 262-473<br />
[[3msx]] - hRhoGAP 20 RhoGAP domain + RhoA<br />
[[2yuy]] - hRhoGAP 21 PDZ domain - NMR<br />
[[2dhj]] - hRhoGAP 21 pleckstrin homology domain - NMR<br />
[[3pp2]] - hRhoGAP 27 pleckstrin homology domain<br />
[[4wpc]] - yRhoGAP 1 F-BARR domain + inositol phosphate<br />
[[1grn]] - hRhoGAP C-terminal + GTP-binding protein<br />


== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]

Latest revision as of 11:00, 7 August 2024

Function

Rho GTPase activating protein (RhoGAP) are one of the main classes of Rho GTPase regulators that are crucial in cell cytoskeletal organization, growth, differentiation, neuronal development and synaptic functions[1],[2]. RhoGAPs contain a RhoGAP domain.

  • RhoGAP7 activates the small GTPases RHOA, RHOB, RHOC and CDC42.
  • RhoGAP9 regulates adhesion of hematopoietic cells to the extracellular matrix.
  • RhoGAP11 causes cell-cycle arrest and apoptosis in response to DNA damage.
  • RhoGAP12 may be involved in suppressing tumor formation.
  • RhoGAP21 involved in cell adhesion, migration, Golgi regulation, cell trafficking and insulin secretion[3].
  • RhoGAP21 involved in cell adhesion, migration, Golgi regulation, cell trafficking and insulin secretion[4].
  • RhoGAP35 involved in cell adhesion, migration and invasion[5].

Relevance

RhoGAPs are present in altered abundance in a variety of human cancers and may serve as targets for cancer therapy[6],[7]. RhoGAP10 variants may be associated with schizophrenia[8].

Structural highlights

The contains a and GDP[9]. Water molecules are shown as red spheres. .

3D structures of Rho GTPase activating protein

Rho GTPase activating protein 3D structures


Human RhoGAP 1 (magenta) complex with RhoA (blue), GDP, MgF3 and Mg+2 ions (PDB code 1ow3)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol. 2003 Jan;13(1):13-22. PMID:12480336
  2. ↑ Tcherkezian J, Lamarche-Vane N. Current knowledge of the large RhoGAP family of proteins. Biol Cell. 2007 Feb;99(2):67-86. doi: 10.1042/BC20060086. PMID:17222083 doi:http://dx.doi.org/10.1042/BC20060086
  3. ↑ Rosa LRO, Soares GM, Silveira LR, Boschero AC, Barbosa-Sampaio HCL. ARHGAP21 as a master regulator of multiple cellular processes. J Cell Physiol. 2018 Nov;233(11):8477-8481. PMID:29856495 doi:10.1002/jcp.26829
  4. ↑ Rosa LRO, Soares GM, Silveira LR, Boschero AC, Barbosa-Sampaio HCL. ARHGAP21 as a master regulator of multiple cellular processes. J Cell Physiol. 2018 Nov;233(11):8477-8481. PMID:29856495 doi:10.1002/jcp.26829
  5. ↑ Sun Y, Du R, Shang Y, Liu C, Zheng L, Sun R, Wang Y, Lu G. Rho GTPase-activating protein 35 suppresses gastric cancer metastasis by regulating cytoskeleton reorganization and epithelial-to-mesenchymal transition. Bioengineered. 2022 Jun;13(6):14605-14615. PMID:35758029 doi:10.1080/21655979.2022.2092677
  6. ↑ Kandpal RP. Rho GTPase activating proteins in cancer phenotypes. Curr Protein Pept Sci. 2006 Aug;7(4):355-65. PMID:16918449
  7. ↑ Song W, Chen J, Li S, Li D, Zhang Y, Zhou H, Yu W, He B, Zhang W, Li L. Rho GTPase Activating Protein 9 (ARHGAP9) in Human Cancers. Recent Pat Anticancer Drug Discov. 2022;17(1):55-65. PMID:34365932 doi:10.2174/1574892816666210806155754
  8. ↑ Sekiguchi M, Sobue A, Kushima I, Wang C, Arioka Y, Kato H, Kodama A, Kubo H, Ito N, Sawahata M, Hada K, Ikeda R, Shinno M, Mizukoshi C, Tsujimura K, Yoshimi A, Ishizuka K, Takasaki Y, Kimura H, Xing J, Yu Y, Yamamoto M, Okada T, Shishido E, Inada T, Nakatochi M, Takano T, Kuroda K, Amano M, Aleksic B, Yamomoto T, Sakuma T, Aida T, Tanaka K, Hashimoto R, Arai M, Ikeda M, Iwata N, Shimamura T, Nagai T, Nabeshima T, Kaibuchi K, Yamada K, Mori D, Ozaki N. ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk. Transl Psychiatry. 2020 Jul 22;10(1):247. PMID:32699248 doi:10.1038/s41398-020-00917-z
  9. ↑ Graham DL, Lowe PN, Grime GW, Marsh M, Rittinger K, Smerdon SJ, Gamblin SJ, Eccleston JF. MgF(3)(-) as a transition state analog of phosphoryl transfer. Chem Biol. 2002 Mar;9(3):375-81. PMID:11927263

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