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
Orthologs
SpeciesHumanMouse
Entrez

29127

26934

Ensembl

ENSG00000161800

ENSMUSG00000023015

UniProt

Q9H0H5

Q9WVM1

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

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

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

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000161800 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023015 - 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. ↑ Touré A, Dorseuil O, Morin L, Timmons P, Jégou B, Reibel L, Gacon G (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, Li E, Hou C, Su Y, 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, Ohi M, Shimura T, Kitajima T, 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, Kawamura M, Kawamoto A, Okugawa Y, 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, Li E, Hou C, Su Y, 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, Wang J, Li E, Hou C, 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, Kehan; Zhou, Danmei; Wang, Meili; Li, Ermin; Hou, Chenjian; Su, Ying; Zou, Qiang; Zhou, Ping; Liu, Xiuping (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, Li E, Hou C, Su Y, 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, Pineau C, Morin L, Dorseuil O, 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, Becq F, Dorseuil O, Gacon G (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. doi:10.1016/j.cub.2013.01.006. PMID 23428321.
  17. ↑ Lee KY, Esmaeili B, Zealley B, Mishima M (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, Li E, Hou C, Su Y, 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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