Rho guanine nucleotide exchange factor: Difference between revisions

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<StructureSection load='3kz1' size='340' side='right' caption='Human Rho guanine nucleotide exchange factor 11 DH/PH domain (grey) complex with  transforming protein RhoA (cyan), GSP (stick model) and Mg+2 ion (green) (PDB code [[3kz1]])' scene=''>
<StructureSection load='3kz1' size='340' side='right' caption='Human Rho guanine nucleotide exchange factor 11 DH/PH domain (grey) complex with  transforming protein RhoA (cyan), GSP and Mg+2 ion (green) (PDB code [[3kz1]])' scene=''>
__TOC__
== Function ==
== Function ==
'''Rho guanine nucleotide exchange factor''' (GEF) stimulate the exchange of the inactive GDP-bound GTPase to its active GTP-bound form.  Binding of GEF to GDP-GTPase catalyzes the dissociation of GDP from the protein<ref>PMID:23303910</ref>.  GEF domains include the catalytic DH/PH (Dbl Homology/Pleckstrin Homology) domain; the CH (Calponin Homology) domain is believed to be involved in calcium regulation; the SH3 domain interacts with proline-rich sequences.
'''Rho guanine nucleotide exchange factor''' (GEF) stimulate the exchange of the inactive GDP-bound GTPase to its active GTP-bound form.  Binding of GEF to GDP-GTPase catalyzes the dissociation of GDP from the protein<ref>PMID:23303910</ref>.  GEF domains include the catalytic DH/PH (Dbl Homology/Pleckstrin Homology) domain; the CH (Calponin Homology) domain is believed to be involved in calcium regulation; the SH3 domain interacts with proline-rich sequences.


*'''Rho guanine nucleotide exchange factor 1''' binds to G proteins and stimulate Rho-dependent signals.<br />
*'''Rho guanine nucleotide exchange factor 1''' binds to G proteins and stimulate Rho-dependent signals.<br />
*'''Rho guanine nucleotide exchange factor 6''' acts on RAC1.<br />
*'''Rho guanine nucleotide exchange factor 3''' acts on RHOA and RHOB involved in bone biology.<br />
*'''Rho guanine nucleotide exchange factor 6''' and '''Rho guanine nucleotide exchange factor 7''' act on Rac1.<br />
*'''Rho guanine nucleotide exchange factor 9''' mutations involved in developmental and epileptic encephalopathy<ref>PMID:35638461</ref>.
*'''Rho guanine nucleotide exchange factor 11''' mediates Rho-myosin light chain signaling pathways at cell-cell junctions<ref>PMID:22665792</ref>.
*'''Rho guanine nucleotide exchange factor 18''' regulates tissue architecture and function via RhoA activation<ref>PMID:23698346</ref>.
*'''Rho guanine nucleotide exchange factor 25''' involved in contraction of vascular smooth muscle.


== Disease ==
== Disease ==
Increased GEF activity is involved in cancer cell proliferation by affecting Rho GTPases <ref>PMID:24037532</ref>.
Increased GEF activity is involved in cancer cell proliferation by affecting Rho GTPases <ref>PMID:24037532</ref>.
 
== 3D Structures of Rho guanine nucleotide exchange factor ==
== Relevance ==
[[Rho guanine nucleotide exchange factor 3D structures]]
 
== Structural highlights ==


</StructureSection>
</StructureSection>


== 3D Structures of Rho guanine nucleotide exchange factor ==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
*Rho guanine nucleotide exchange factor 1 (P115-RhoGEF)
**[[1iap]] – hGEF N terminal - human<br />
**[[3odo]], [[3odw]], [[3odx]] – hGEF DH/PH domain <br />
**[[3p6a]] – hGEF DH/PH domain (mutant)<br />
**[[1shz]], [[3ab3]] – hGEF N terminal + guanine nucleotide-binding protein<br />
*Rho guanine nucleotide exchange factor 4 (Asef)
**[[2dx1]], [[2pz1]] – hGEF <br />
**[[3nmx]], [[3nmz]] – hGEF + APC variant protein<br />
*Rho guanine nucleotide exchange factor 6
**[[1ujy]] – hGEF SH3 domain - NMR<br />
**[[1wyr]] – hGEF CH domain - NMR<br />
*Rho guanine nucleotide exchange factor 7 (β-PIX)
**[[1by1]] – hGEF DH domain - NMR<br />
**[[2l3g]] – hGEF CH domain - NMR<br />
**[[2esw]] – GEF SH3 domain – mouse<br />
**[[2g6f]] – rGEF SH3 domain – rat<br />
**[[2w6b]] – rGEF coiled-coil domain  <br />
*Rho guanine nucleotide exchange factor 7 complex with peptide
**[[2ak5]] – hGEF SH3 domain + CBL-b peptide <br />
**[[2df6]] – hGEF SH3 domain + PAK-1 peptide <br />
**[[1zsg]] – hGEF residues 179-243 + PAK-1 peptide – NMR<br />
**[[2p4r]] – rGEF SH3 domain + E3 ubiquitin protein ligase peptide <br />
**[[3l4f]] – rGEF coiled-coil domain + SHANK1 PDZ domain <br />
*Rho guanine nucleotide exchange factor 8 (PRONE8)
**[[2ntx]] – AtGEF PRONE domain – ''Arabidopasis thaliana''<br />
**[[2wbl]] – AtGEF PRONE domain + GTPase ROP7 <br />
**[[2nty]] – AtGEF PRONE domain + GTPase ROP4 + GDP <br />
**[[3eo2]] – hGEF residues 161-373 <br />
**[[4xh9]] – hGEF DH/PH domain + transforming protein RhoA <br />
*Rho guanine nucleotide exchange factor 9 (collybistin)
**[[2ysq]] – hGEF SH3 domain - NMR<br />
**[[4mt6]], [[4mt7]] – rGEF (mutant)<br />
**[[2dfk]] – rGEF + CDC42 <br />
*Rho guanine nucleotide exchange factor 11
**[[2dls]] – hGEF PDZ domain - NMR<br />
**[[3kz1]], [[3t06]] – hGEF DH/PH domain + transforming protein RhoA <br />
**[[1xcg]] – hGEF DH/PH domain + transforming protein RhoA - NMR<br />
**[[3cx6]] – rGEF RGS domain + guanine nucleotide-binding protein <br />
*Rho guanine nucleotide exchange factor 12 (Leukemia-associated RhoGEF)
**[[1txd]] – hGEF DH/PH domain <br />
**[[2omj]] – hGEF PDZ domain <br />
**[[1x86]] – hGEF DH/PH domain (mutant) + transforming protein RhoA <br />
**[[2os6]] – hGEF PDZ domain + plexin peptide – NMR<br />
*Rho guanine nucleotide exchange factor 16
**[[1x6b]] – hGEF SH3 domain - NMR<br />
}}
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]

Latest revision as of 13:02, 6 August 2024

Function

Rho guanine nucleotide exchange factor (GEF) stimulate the exchange of the inactive GDP-bound GTPase to its active GTP-bound form. Binding of GEF to GDP-GTPase catalyzes the dissociation of GDP from the protein[1]. GEF domains include the catalytic DH/PH (Dbl Homology/Pleckstrin Homology) domain; the CH (Calponin Homology) domain is believed to be involved in calcium regulation; the SH3 domain interacts with proline-rich sequences.

  • Rho guanine nucleotide exchange factor 1 binds to G proteins and stimulate Rho-dependent signals.
  • Rho guanine nucleotide exchange factor 3 acts on RHOA and RHOB involved in bone biology.
  • Rho guanine nucleotide exchange factor 6 and Rho guanine nucleotide exchange factor 7 act on Rac1.
  • Rho guanine nucleotide exchange factor 9 mutations involved in developmental and epileptic encephalopathy[2].
  • Rho guanine nucleotide exchange factor 11 mediates Rho-myosin light chain signaling pathways at cell-cell junctions[3].
  • Rho guanine nucleotide exchange factor 18 regulates tissue architecture and function via RhoA activation[4].
  • Rho guanine nucleotide exchange factor 25 involved in contraction of vascular smooth muscle.

Disease

Increased GEF activity is involved in cancer cell proliferation by affecting Rho GTPases [5].

3D Structures of Rho guanine nucleotide exchange factor

Rho guanine nucleotide exchange factor 3D structures


Human Rho guanine nucleotide exchange factor 11 DH/PH domain (grey) complex with transforming protein RhoA (cyan), GSP and Mg+2 ion (green) (PDB code 3kz1)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Cherfils J, Zeghouf M. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev. 2013 Jan;93(1):269-309. doi: 10.1152/physrev.00003.2012. PMID:23303910 doi:http://dx.doi.org/10.1152/physrev.00003.2012
  2. ↑ Yang H, Liao H, Gan S, Xiao T, Wu L. ARHGEF9 gene variant leads to developmental and epileptic encephalopathy: Genotypic phenotype analysis and treatment exploration. Mol Genet Genomic Med. 2022 Jul;10(7):e1967. PMID:35638461 doi:10.1002/mgg3.1967
  3. ↑ Itoh M, Tsukita S, Yamazaki Y, Sugimoto H. Rho GTP exchange factor ARHGEF11 regulates the integrity of epithelial junctions by connecting ZO-1 and RhoA-myosin II signaling. Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):9905-10. PMID:22665792 doi:10.1073/pnas.1115063109
  4. ↑ Herder C, Swiercz JM, Müller C, Peravali R, Quiring R, Offermanns S, Wittbrodt J, Loosli F. ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation. Development. 2013 Jul;140(13):2787-97. PMID:23698346 doi:10.1242/dev.096487
  5. ↑ Cook DR, Rossman KL, Der CJ. Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease. Oncogene. 2014 Jul 31;33(31):4021-35. doi: 10.1038/onc.2013.362. Epub 2013 Sep, 16. PMID:24037532 doi:http://dx.doi.org/10.1038/onc.2013.362

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Michal Harel, Joel L. Sussman
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