Ras-related C3 botulinum toxin substrate 3 (Rac3) is a G protein that in humans is encoded by the RAC3 gene.[5] It is an important component of intracellular signalling pathways. Rac3 is a member of the Rac subfamily of the Rho family of small G proteins.[6][7] Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.[5]

RAC3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRAC3, ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3), Rac family small GTPase 3
External IDsOMIM: 602050; MGI: 2180784; HomoloGene: 68433; GeneCards: RAC3; OMA:RAC3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005052
NM_001316307

NM_133223

RefSeq (protein)

NP_001303236
NP_005043

NP_573486

Location (UCSC)Chr 17: 82.03 – 82.03 MbChr 11: 120.61 – 120.61 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interactions

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RAC3 has been shown to interact with CIB1[8] and HNF1A.[9] RAC3 also interacts with Nrf2 proteins.[10] ETAR, ILK, and β-arr1 interact with RAC3 as well.[11]

Location

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RAC3 gene is located in the third sub-band of the fifth band in the second region of the q arm on chromosome 17. There's many tumor suppressor genes that are located around the RAC3 gene.[12]

Therapeutic Use

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Since the RAC3 gene is over-expressed in carcinoma cells, it can function as a therapeutic target for the treatment of different cancer such as lung adenocarcinoma. To become invasive, epithelial cells have to transform into mesenchymal cells and the transformation is regulated by the RAC3 gene. As a result, if the RAC3 gene is silenced, lung adenocarcinoma cells cannot metastasize. In addition, drugs designed to silence the RAC3 gene lead to the apoptosis of tumor cells, thus preventing the cells from colonizing.[13]

Pathological mutations

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Mutations of the RAC3 gene may result in neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, first described in 2018 by White et al.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000169750Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018012Ensembl, 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. ^ a b "Entrez Gene: RAC3 ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)".
  6. ^ Courjal F, Chuchana P, Theillet C, Fort P (September 1997). "Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes". Genomics. 44 (2): 242–6. doi:10.1006/geno.1997.4871. PMID 9299243.
  7. ^ Haataja L, Groffen J, Heisterkamp N (August 1997). "Characterization of RAC3, a novel member of the Rho family". The Journal of Biological Chemistry. 272 (33): 20384–8. doi:10.1074/jbc.272.33.20384. PMID 9252344.
  8. ^ Haataja L, Kaartinen V, Groffen J, Heisterkamp N (March 2002). "The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading". The Journal of Biological Chemistry. 277 (10): 8321–8. doi:10.1074/jbc.M105363200. PMID 11756406. yes
  9. ^ Soutoglou E, Papafotiou G, Katrakili N, Talianidis I (April 2000). "Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins". The Journal of Biological Chemistry. 275 (17): 12515–20. doi:10.1074/jbc.275.17.12515. PMID 10777539. yes
  10. ^ Kim JH, Yu S, Chen JD, Kong AN (January 2013). "The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains". Oncogene. 32 (4): 514–27. doi:10.1038/onc.2012.59. PMC 3538952. PMID 22370642.
  11. ^ Masi I, Caprara V, Spadaro F, Chellini L, Sestito R, Zancla A, et al. (March 2021). "Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK". Cell Reports. 34 (9): 108800. doi:10.1016/j.celrep.2021.108800. PMID 33657382.
  12. ^ Morris CM, Haataja L, McDonald M, Gough S, Markie D, Groffen J, Heisterkamp N (2000). "The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours". Cytogenetics and Cell Genetics. 89 (1–2): 18–23. doi:10.1159/000015583. PMID 10894930. S2CID 22901214.
  13. ^ de Curtis I (September 2019). "The Rac3 GTPase in Neuronal Development, Neurodevelopmental Disorders, and Cancer". Cells. 8 (9): 1063. doi:10.3390/cells8091063. PMC 6770886. PMID 31514269.

Further reading

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