Rnd3

Last updated
RND3
Protein RND3 PDB 1gwn.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RND3 , ARHE, Rho8, RhoE, memB, Rnd3, Rho family GTPase 3
External IDs OMIM: 602924; MGI: 1921444; HomoloGene: 21074; GeneCards: RND3; OMA:RND3 - orthologs
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 Mb Chr 2: 51.02 – 51.04 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

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]

Related Research Articles

The Rho family of GTPases is a family of small signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog is a protein that in humans is encoded by the CDC42 gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in humans

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">ROCK1</span> Protein

ROCK1 is a protein serine/threonine kinase also known as rho-associated, coiled-coil-containing protein kinase 1. Other common names are ROKβ and P160ROCK. ROCK1 is a major downstream effector of the small GTPase RhoA and is a regulator of the actomyosin cytoskeleton which promotes contractile force generation. ROCK1 plays a role in cancer and in particular cell motility, metastasis, and angiogenesis.

<span class="mw-page-title-main">RAP1A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rap-1A is a protein that in humans is encoded by the RAP1A gene.

<span class="mw-page-title-main">RALA</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Ral-A (RalA) is a protein that in humans is encoded by the RALA gene on chromosome 7. This protein is one of two paralogs of the Ral protein, the other being RalB, and part of the Ras GTPase family. RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. Its biological role thus implicates it in many cancers.

<span class="mw-page-title-main">RhoG</span> Protein-coding gene in the species Homo sapiens

RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.

<span class="mw-page-title-main">Citron kinase</span> Enzyme found in humans

Citron Rho-interacting kinase is an enzyme that in humans is encoded by the CIT gene.

<span class="mw-page-title-main">Rnd1</span> Protein-coding gene in the species Homo sapiens

Rnd1 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND1.

<span class="mw-page-title-main">ARHGAP5</span> Protein-coding gene in the species Homo sapiens

Rho GTPase-activating protein 5 is an enzyme that in humans is encoded by the ARHGAP5 gene.

<span class="mw-page-title-main">RhoD</span> Protein-coding gene in the species Homo sapiens

RhoD is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOD.

<span class="mw-page-title-main">Rnd2</span> Protein-coding gene in the species Homo sapiens

Rnd2 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND2.

<span class="mw-page-title-main">RhoH</span> Protein-coding gene in the species Homo sapiens

RhoH is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOH.

Rac is a subfamily of the Rho family of GTPases, small signaling G proteins. Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to GDP and activated once GEFs remove GDP, permitting GTP to bind. When bound to GTP, Rac is activated. In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin Cytoskeleton. By changing the cytoskeletal dynamics within the cell, Rac-GTPases are able to facilitate the recruitment of neutrophils to the infected tissues, and to regulate degranulation of azurophil and integrin-dependent phagocytosis.

<span class="mw-page-title-main">UBXD5</span> Protein-coding gene in the species Homo sapiens

UBX domain-containing protein 11 is a protein that in humans is encoded by the UBXN11 gene.

<span class="mw-page-title-main">GNA12</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.

<span class="mw-page-title-main">Rho-associated protein kinase</span>

Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton.

<span class="mw-page-title-main">Alan Hall</span> British cell biologist and professor

Alan Hall FRS was a British cell biologist and a biology professor at the Sloan-Kettering Institute, where he was chair of the Cell Biology program. Hall was elected a Fellow of the Royal Society in 1999.

<span class="mw-page-title-main">PLEKHG2</span> Protein-coding gene in the species Homo sapiens

Pleckstrin homology domain containing, family G member 2 (PLEKHG2) is a protein that in humans is encoded by the PLEKHG2 gene. It is sometimes written as ARHGEF42, FLJ00018.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000115963 Ensembl, May 2017
  2. 1 2 3 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. Bibcode:2003CBio...13.1106W. 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