RND3
Protein RND3 PDB 1gwn.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRND3, ARHE, Rho8, RhoE, memB, Rnd3, Rho family GTPase 3
External IDsOMIM: 602924 MGI: 1921444 HomoloGene: 21074 GeneCards: RND3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005168
NM_001254738

NM_028810

RefSeq (protein)

NP_001241667
NP_005159

NP_083086

Location (UCSC)Chr 2: 150.47 – 150.54 MbChr 2: 51.02 – 51.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Rnd3 is a small (~21 kDa) signaling G protein (to be specific, a GTPase), and is a member of the Rnd subgroup of the Rho family of GTPases.[5] It is encoded by the gene RND3.[6]

Like other members of the Rho family of Ras-related GTPases it regulates the organization of the actin cytoskeleton in response to extracellular growth factors.

Regulation

Most Rho family members cycle between an inactive GDP-bound form and an active GTP-bound form. However, members of the Rnd subgroup of the Rho family are exceptions to this, binding detectably only to GTP, while having low GTPase activity, if any.[7] Instead, Rnd family proteins are regulated through other mechanisms that control their production, degradation, phosphorylation, and localization.[8]


Interactions

In its GTP-bound form, RhoA exposes regions that allow it to interact with downstream targets. Rnd3 contains a region which is similar to the one RhoA exposes for interaction with ROCK1, allowing Rnd3 to compete with RhoA for interaction with ROCK1. By binding to ROCK1, Rnd3 inhibits it from phosphorylating downstream targets necessary for stress fiber formation. Rnd3 is also directly involved in controlling RhoA activity through suppression of PLEKHG5[9] and activation of ARHGAP5.[10] Interaction with UBXD5 has also been shown.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115963 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017144 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Ridley AJ (October 2006). "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends in Cell Biology. 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. PMID 16949823.
  6. ^ "Entrez Gene: RND3 Rho family GTPase 3".
  7. ^ Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Molecular and Cellular Biology. 23 (12): 4219–29. doi:10.1128/MCB.23.12.4219-4229.2003. PMC 156133. PMID 12773565.
  8. ^ Chardin P (January 2006). "Function and regulation of Rnd proteins". Nature Reviews. Molecular Cell Biology. 7 (1): 54–62. doi:10.1038/nrm1788. PMID 16493413. S2CID 90941.
  9. ^ Goh LL, Manser E (August 2010). Ouchi T (ed.). "The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin-related domain". PLOS ONE. 5 (8): e12409. Bibcode:2010PLoSO...512409G. doi:10.1371/journal.pone.0012409. PMC 2928299. PMID 20811643.
  10. ^ Wennerberg K, Forget MA, Ellerbroek SM, Arthur WT, Burridge K, Settleman J, et al. (July 2003). "Rnd proteins function as RhoA antagonists by activating p190 RhoGAP". Current Biology. 13 (13): 1106–15. doi:10.1016/S0960-9822(03)00418-4. PMC 6918695. PMID 12842009.
  11. ^ Katoh H, Harada A, Mori K, Negishi M (May 2002). "Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers". Molecular and Cellular Biology. 22 (9): 2952–64. doi:10.1128/MCB.22.9.2952-2964.2002. PMC 133765. PMID 11940653.

Further reading