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RACGAP1

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RACGAP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRACGAP1, CYK4, HsCYK-4, ID-GAP, MgcRacGAP, Rac GTPase activating protein 1, CDAN3B
External IDsOMIM: 604980; MGI: 1349423; HomoloGene: 8077; GeneCards: RACGAP1; OMA:RACGAP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001253808
NM_001253809
NM_012025

RefSeq (protein)

NP_001240737
NP_001240738
NP_036155

Location (UCSC)Chr 12: 49.98 – 50.03 MbChr 15: 99.52 – 99.55 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Rac GTPase-activating protein 1 is an enzyme that in humans is encoded by the RACGAP1 gene.[5]

Function

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Rho GTPases control a variety of cellular processes. There are 3 subtypes of Rho GTPases in the Ras superfamily of small G proteins: RHO (see MIM 165370), RAC (see RAC1; MIM 602048), and CDC42 (MIM 116952). GTPase-activating proteins (GAPs) bind activated forms of Rho GTPases and stimulate GTP hydrolysis. Through this catalytic function, Rho GAPs negatively regulate Rho-mediated signals. GAPs may also serve as effector molecules and play a role in signaling downstream of Rho and other Ras-like GTPases.[supplied by OMIM].[6] Over-expression of RACGAP1 is observed in multiple human cancers including breast cancer,[7] gastric cancer[8] and colorectal cancer.[9] Evidence show that RACGAP1 can modulate mitochondrial quality control by stimulating mitopahy and mitochondrial biogenesis in breast cancer.[10][11] Knocking out RACGAP1 in vitro using CRISPR/Cas9 leads to cytokinesis failure.[12]

Interactions

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RACGAP1 has been shown to interact with ECT2,[13] Rnd2[14] and SLC26A8.[15]

During cytokinesis, RACGAP1 has been shown to interact with KIF23 to form the centralspindlin complex.[16] This complex is essential for the formation of the central spindle. RACGAP1 also interacts with PRC1 to stabilize and maintain the central spindle as anaphase proceeds.[17] RACGAP1 can also interact with ECT2 during anaphase of cytokinesis, loss of RACGAP1 leads to cytokinesis failure.[18]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000161800Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023015Ensembl, 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. ^ Touré A, Dorseuil O, Morin L, et al. (March 1998). "MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells". The Journal of Biological Chemistry. 273 (11): 6019–23. doi:10.1074/jbc.273.11.6019. PMID 9497316.
  6. ^ "Entrez Gene: RACGAP1 Rac GTPase activating protein 1".
  7. ^ Ren K, Zhou D, Wang M, et al. (March 2021). "RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis". Experimental Cell Research. 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. PMID 33485843. S2CID 231701513.
  8. ^ Saigusa S, Tanaka K, Mohri Y, et al. (January 2015). "Clinical significance of RacGAP1 expression at the invasive front of gastric cancer". Gastric Cancer. 18 (1): 84–92. doi:10.1007/s10120-014-0355-1. PMID 24615626. S2CID 13008506.
  9. ^ Imaoka H, Toiyama Y, Saigusa S, et al. (March 2015). "RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer". Carcinogenesis. 36 (3): 346–54. doi:10.1093/carcin/bgu327. PMID 25568185.
  10. ^ Ren K, Zhou D, Wang M, et al. (March 2021). "RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis". Experimental Cell Research. 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. PMID 33485843. S2CID 231701513.
  11. ^ Zhou D, Ren K, Wang M, et al. (February 2021). "Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission". Molecular Oncology. 15 (2): 543–559. doi:10.1002/1878-0261.12866. ISSN 1574-7891. PMC 7858103. PMID 33252198.
  12. ^ Ren K, Zhou D, Wang M, et al. (2021-03-01). "RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis". Experimental Cell Research. 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. ISSN 0014-4827. PMID 33485843. S2CID 231701513.
  13. ^ Ren K, Zhou D, Wang M, et al. (March 2021). "RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis". Experimental Cell Research. 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. PMID 33485843. S2CID 231701513.
  14. ^ Naud N, Touré A, Liu J, et al. (May 2003). "Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells". The Biochemical Journal. 372 (Pt 1): 105–112. doi:10.1042/BJ20021652. PMC 1223378. PMID 12590651.
  15. ^ Toure A, Morin L, Pineau C, et al. (June 2001). "Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling". The Journal of Biological Chemistry. 276 (23): 20309–20315. doi:10.1074/jbc.M011740200. PMID 11278976.
  16. ^ Glotzer M (February 2013). "Cytokinesis: centralspindlin moonlights as a membrane anchor". Current Biology. 23 (4): R145-7. Bibcode:2013CBio...23.R145G. doi:10.1016/j.cub.2013.01.006. PMID 23428321.
  17. ^ Lee KY, Esmaeili B, Zealley B, et al. (June 2015). "Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle". Nature Communications. 6: 7290. Bibcode:2015NatCo...6.7290L. doi:10.1038/ncomms8290. PMC 4557309. PMID 26088160.
  18. ^ Ren K, Zhou D, Wang M, et al. (March 2021). "RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis". Experimental Cell Research. 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. PMID 33485843. S2CID 231701513.

Further reading

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