RACGAP1

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

RACGAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2OVJ, 3W6R, 3WPQ, 3WPS, 4B6D, 5C2J, 5C2K
Identifiers
Aliases	RACGAP1, CYK4, HsCYK-4, ID-GAP, MgcRacGAP, Rac GTPase activating protein 1
External IDs	OMIM: 604980 MGI: 1349423 HomoloGene: 8077 GeneCards: RACGAP1
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.12 Start 49,976,923 bp[1] End 50,033,136 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F1 Start 99,620,496 bp[2] End 99,651,656 bp[2]
Gene ontology Molecular function • microtubule binding • alpha-tubulin binding • metal ion binding • GO:0001948 protein binding • beta-tubulin binding • gamma-tubulin binding • protein kinase binding • phosphatidylinositol-3,4,5-trisphosphate binding • lipid binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity Cellular component • cytoplasm • cytosol • centralspindlin complex • membrane • extrinsic component of cytoplasmic side of plasma membrane • cell membrane • spindle • nucleoplasm • Acrosome • spindle midzone • cleavage furrow • mitotic spindle • microtubule • extracellular exosome • cytoskeleton • cell nucleus • cytoplasmic vesicle • midbody • Flemming body Biological process • cell differentiation • GO:0007243 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 • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • retrograde vesicle-mediated transport, Golgi to ER • regulation of embryonic development • transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	29127	26934
Ensembl	ENSG00000161800	ENSMUSG00000023015
UniProt	Q9H0H5	Q9WVM1
RefSeq (mRNA)	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
RefSeq (protein)	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
Location (UCSC)	Chr 12: 49.98 – 50.03 Mb	Chr 15: 99.62 – 99.65 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Interactions

RACGAP1 has been shown to interact with Rnd2[7] and SLC26A8.[8]

During cytokinesis, RACGAP1 has been shown to interact with KIF23 to form the centralspindlin complex.[9] 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.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000161800 - Ensembl, May 2017
2. 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. Naud N, Touré A, Liu J, Pineau C, Morin L, Dorseuil O, Escalier D, Chardin P, Gacon G (May 2003). "Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells". The Biochemical Journal. 372 (Pt 1): 105–12. doi:10.1042/BJ20021652. PMC 1223378. PMID 12590651.
8. 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): 20309–15. doi:10.1074/jbc.M011740200. PMID 11278976.
9. 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.
10. Lee KY, Esmaeili B, Zealley B, Mishima M (2015). "Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle". Nature Communications. 6: 7290. doi:10.1038/ncomms8290. PMC 4557309. PMID 26088160.

Further reading

• 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): 171–4. 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): 8288–95. 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): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Nagata Ki, Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T, Hirokawa N, Hall A (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): 149–58. 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): 1395–404. doi:10.1093/emboj/17.5.1395. PMC 1170487. PMID 9482736.
• Abo A, Qu J, Cammarano MS, Dan C, Fritsch A, Baud V, Belisle B, Minden A (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): 6527–40. doi:10.1093/emboj/17.22.6527. PMC 1171000. PMID 9822598.
• Zuber J, Tchernitsa OI, Hinzmann B, Schmitz AC, Grips M, Hellriegel M, Sers C, Rosenthal A, Schäfer R (February 2000). "A genome-wide survey of RAS transformation targets". Nature Genetics. 24 (2): 144–52. doi:10.1038/72799. PMID 10655059.
• Das B, Shu X, Day GJ, Han J, Krishna UM, Falck JR, Broek D (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): 15074–81. 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): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331.
• Kawashima T, Hirose K, Satoh T, Kaneko A, Ikeda Y, Kaziro Y, Nosaka T, Kitamura T (September 2000). "MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells". Blood. 96 (6): 2116–24. PMID 10979956.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. 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): 5821–8. 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): 18303–12. doi:10.1074/jbc.M011368200. PMID 11278894.
• 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): 20309–15. doi:10.1074/jbc.M011740200. PMID 11278976.
• 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): 836–45. 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): 645–51. 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): 4901–13. doi:10.1242/jcs.00219. PMID 12432077.
• Jantsch-Plunger V, Gönczy P, Romano A, Schnabel H, Hamill D, Schnabel R, Hyman AA, Glotzer M (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): 1391–404. doi:10.1083/jcb.149.7.1391. PMC 2175131. PMID 10871280.