RACGAP1

RACGAP1
Identifiers
Aliases	RACGAP1, CYK4, HsCYK-4, ID-GAP, MgcRacGAP, Rac GTPase activating protein 1, CDAN3B
External IDs	OMIM: 604980; MGI: 1349423; GeneCards: RACGAP1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2OVJ, 3W6R, 3WPQ, 3WPS, 4B6D, 5C2J, 5C2K
Gene location (Human)
Chr.	Chromosome 12 (human)
End	50,033,136 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	99,549,537 bp
RNA expression pattern
	Top expressed in
	ventricular zone; ; ganglionic eminence; ; trabecular bone; ; sperm; ; secondary oocyte; ; oral cavity; ; bone marrow; ; amniotic fluid; ; gonad; ; right testis;
	Top expressed in
	ventricular zone; ; spermatocyte; ; spermatid; ; endocardial cushion; ; yolk sac; ; dermis; ; atrioventricular valve; ; atrium; ; thymus; ; ganglionic eminence;
	More reference expression data
	n/a
Gene ontology
Molecular function	microtubule binding; alpha-tubulin binding; metal ion binding; protein binding; beta-tubulin binding; gamma-tubulin binding; protein kinase binding; phosphatidylinositol-3,4,5-trisphosphate binding; lipid binding; GTPase activator activity;
Cellular component	cytoplasm; cytosol; centralspindlin complex; membrane; extrinsic component of cytoplasmic side of plasma membrane; plasma membrane; spindle; nucleoplasm; acrosomal vesicle; spindle midzone; cleavage furrow; mitotic spindle; microtubule; extracellular exosome; cytoskeleton; nucleus; cytoplasmic vesicle; midbody; Flemming body;
Biological process	cell differentiation; intracellular signal transduction; antigen processing and presentation of exogenous peptide antigen via MHC class II; mitotic spindle midzone assembly; sulfate transport; mitotic cytokinesis; ion transport; cell division; positive regulation of cytokinesis; multicellular organism development; microtubule-based movement; actomyosin contractile ring assembly; spermatogenesis; neuroblast proliferation; cell cycle; regulation of attachment of spindle microtubules to kinetochore; regulation of small GTPase mediated signal transduction; signal transduction; positive regulation of GTPase activity; retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; regulation of embryonic development; transport;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	29127
	26934
	ENSG00000161800
	ENSMUSG00000023015
	Q9H0H5
	Q9WVM1
NM_001126103; NM_001126104; NM_013277; NM_001319999; NM_001320000;
	NM_001320001; NM_001320002; NM_001320003; NM_001320004; NM_001320005; NM_001320006; NM_001320007
	NM_001253808; NM_001253809; NM_012025
NP_001119575; NP_001119576; NP_001306928; NP_001306929; NP_001306930;
	NP_001306931; NP_001306932; NP_001306933; NP_001306934; NP_001306935; NP_001306936; NP_037409
	NP_001240737; NP_001240738; NP_036155
	Wikidata
View/Edit Human	View/Edit Mouse

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

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].

Clinical significance

Over-expression of RACGAP1 is observed in multiple human cancers including breast cancer, gastric cancer and colorectal cancer. Evidence show that RACGAP1 can modulate mitochondrial quality control by stimulating mitophagy and mitochondrial biogenesis in breast cancer. Knocking out RACGAP1 in vitro using CRISPR/Cas9 leads to cytokinesis failure.

Interactions

RACGAP1 has been shown to interact with ECT2, Rnd2 and SLC26A8.

During cytokinesis, RACGAP1 has been shown to interact with KIF23 to form the centralspindlin complex. 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. RACGAP1 can also interact with ECT2 during anaphase of cytokinesis, loss of RACGAP1 leads to cytokinesis failure.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000161800 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023015 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Touré A, Dorseuil O, Morin L, Timmons P, Jégou B, Reibel 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): 6019–6023. doi:10.1074/jbc.273.11.6019. PMID 9497316.
↑ "Entrez Gene: RACGAP1 Rac GTPase activating protein 1".
1 2 3 4 5 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.
↑ 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.
↑ 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): 346–354. doi:10.1093/carcin/bgu327. PMID 25568185.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Gerwins P, Blank JL, Johnson GL (March 1997). "Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway". The Journal of Biological Chemistry. 272 (13): 8288–8295. doi:10.1074/jbc.272.13.8288. PMID 9079650.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Nagata K, Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T, et al. (January 1998). "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3". The EMBO Journal. 17 (1): 149–158. doi:10.1093/emboj/17.1.149. PMC 1170366. PMID 9427749.
Tapon N, Nagata K, Lamarche N, Hall A (March 1998). "A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways". The EMBO Journal. 17 (5): 1395–1404. doi:10.1093/emboj/17.5.1395. PMC 1170487. PMID 9482736.
Abo A, Qu J, Cammarano MS, Dan C, Fritsch A, Baud V, et al. (November 1998). "PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia". The EMBO Journal. 17 (22): 6527–6540. doi:10.1093/emboj/17.22.6527. PMC 1171000. PMID 9822598.
Zuber J, Tchernitsa OI, Hinzmann B, Schmitz AC, Grips M, Hellriegel M, et al. (February 2000). "A genome-wide survey of RAS transformation targets". Nature Genetics. 24 (2): 144–152. doi:10.1038/72799. PMID 10655059. S2CID 21887748.
Das B, Shu X, Day GJ, Han J, Krishna UM, Falck JR, et al. (May 2000). "Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding". The Journal of Biological Chemistry. 275 (20): 15074–15081. doi:10.1074/jbc.M907269199. PMID 10748082.
Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O (April 2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (2): 143–150. doi:10.1093/dnares/7.2.143. PMID 10819331.
Kawashima T, Hirose K, Satoh T, Kaneko A, Ikeda Y, Kaziro Y, et al. (September 2000). "MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells". Blood. 96 (6): 2116–2124. doi:10.1182/blood.V96.6.2116. PMID 10979956.
Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Hirose K, Kawashima T, Iwamoto I, Nosaka T, Kitamura T (February 2001). "MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody". The Journal of Biological Chemistry. 276 (8): 5821–5828. doi:10.1074/jbc.M007252200. PMID 11085985.
Caloca MJ, Wang H, Delemos A, Wang S, Kazanietz MG (May 2001). "Phorbol esters and related analogs regulate the subcellular localization of beta 2-chimaerin, a non-protein kinase C phorbol ester receptor". The Journal of Biological Chemistry. 276 (21): 18303–18312. doi:10.1074/jbc.M011368200. PMID 11278894.
Mishima M, Kaitna S, Glotzer M (January 2002). "Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity". Developmental Cell. 2 (1): 41–54. doi:10.1016/S1534-5807(01)00110-1. PMID 11782313.
Vikis HG, Li W, Guan KL (April 2002). "The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding". Genes & Development. 16 (7): 836–845. doi:10.1101/gad.966402. PMC 186329. PMID 11937491.
Kitamura T, Kawashima T, Minoshima Y, Tonozuka Y, Hirose K, Nosaka T (December 2001). "Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation". Cell Structure and Function. 26 (6): 645–651. doi:10.1247/csf.26.645. PMID 11942621.
Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". Journal of Cell Science. 115 (Pt 24): 4901–4913. doi:10.1242/jcs.00219. PMID 12432077.
Jantsch-Plunger V, Gönczy P, Romano A, Schnabel H, Hamill D, Schnabel R, et al. (June 2000). "CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis". The Journal of Cell Biology. 149 (7): 1391–1404. doi:10.1083/jcb.149.7.1391. PMC 2175131. PMID 10871280.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000161800 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[Touré_1998-5] Touré A, Dorseuil O, Morin L, Timmons P, Jégou B, Reibel 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): 6019–6023. doi:10.1074/jbc.273.11.6019. PMID 9497316.

[entrez-6] "Entrez Gene: RACGAP1 Rac GTPase activating protein 1".

[Ren_2021-7] 1 2 3 4 5 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): 346–354. doi:10.1093/carcin/bgu327. PMID 25568185.

[10] 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.

[Naud_2003-11] 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.

[Toure_2001-12] 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.

[cytokinesis-13] 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.

[14] 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.

RACGAP1

Function

Clinical significance

Interactions

References

Further reading