RHOA

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Ras homolog family member A

PDB rendering based on 1a2b.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsRHOA; ARH12; ARHA; RHO12; RHOH12
External IDsOMIM: 165390 MGI: 1096342 HomoloGene: 68986 ChEMBL: 6052 GeneCards: RHOA Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez38711848
EnsemblENSG00000067560ENSMUSG00000007815
UniProtP61586Q9QUI0
RefSeq (mRNA)NM_001664NM_016802
RefSeq (protein)NP_001655NP_058082
Location (UCSC)Chr 3:
49.4 – 49.45 Mb		Chr 9:
108.31 – 108.34 Mb
PubMed search
This box:

Ras homolog gene family, member A (RhoA) is a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers. In humans, it is encoded by the gene RHOA.[1]

It acts upon two known effector proteins: ROCK1 (Rho-associated, coiled-coil containing protein kinase 1) and DIAPH1 (diaphanous homolog 1 (Drosophila)).

RhoA is part of a larger family of related proteins known as the Ras superfamily; proteins involved in the regulation and timing of cell division.

RhoA Pathway

Molecules act on various receptors, such as NgR1, LINGO1, p75, TROY and other unknown receptors (e.g. by CSPGs), which stimulates RhoA. RhoA activates ROCK (RhoA kinase) which stimulates LIM kinase, which then stimulates cofilin, which effectively reorganizes the actin cytoskeleton of the cell.[1] In the case of neurons, activation of this pathway results in growth cone collapse, therefore inhibits the growth and repair of neural pathways and axons. Inhibition of this pathway by its various components usually results in some level of improved re-myelination.[2][3][4][5] After global ischemia, hyperbaric oxygen (at least at 3 ATA) appears to partially suppress expression of RhoA, in addition to Nogo protein (Reticulon 4), and a subunit of its receptor Ng-R.[6]

Interactions

RHOA has been shown to interact with Phospholipase D1,[7][8] PLCG1,[9] ARHGAP5,[10] ARHGAP1,[11][12][13][14] TRPC1,[15] ITPR1,[15][16] DIAPH1,[16] GEFT,[17] ARHGEF3,[18] ARHGEF12,[19] ARHGDIA,[20][21][22][23][24] KCNA2,[25] RAP1GDS1,[26] DGKQ,[27] TRIO,[28] ROCK1,[29][30] ARHGEF11,[31] RICS,[32][33][33] PKN2,[34][35][36] Protein kinase N1,[16][35][37] CIT[16][38] and KTN1.[39][40][41]

References

  1. ↑ 1.0 1.1 Kiss C, Li J, Szeles A, Gizatullin RZ, Kashuba VI, Lushnikova T, Protopopov AI, Kelve M, Kiss H, Kholodnyuk ID, Imreh S, Klein G, Zabarovsky ER (1997). "Assignment of the ARHA and GPX1 genes to human chromosome bands 3p21.3 by in situ hybridization and with somatic cell hybrids". Cytogenet. Cell Genet. 79 (3–4): 228–230. doi:10.1159/000134729. PMID 9605859. 
  2. ↑ Yiu G, He Z (August 2006). "Glial inhibition of CNS axon regeneration". Nat. Rev. Neurosci. 7 (8): 617–627. doi:10.1038/nrn1956. PMC 2693386. PMID 16858390. 
  3. ↑ Bradbury EJ, McMahon SB (August 2006). "Spinal cord repair strategies: why do they work?". Nat. Rev. Neurosci. 7 (8): 644–653. doi:10.1038/nrn1964. PMID 16858392. 
  4. ↑ Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC (July 2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination". Nat. Neurosci. 7 (7): 736–744. doi:10.1038/nn1261. PMID 15184901. 
  5. ↑ Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME (November 1995). "Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors". Nature 378 (6556): 498–501. doi:10.1038/378498a0. PMID 7477407. 
  6. ↑ Yiu G, He Z (September 2003). "Glial inhibition of CNS axon regeneration". Biochem. Biophys. Res. Commun. 309 (2): 368–76. doi:10.1016/j.bbrc.2003.08.006. PMID 12951059. 
  7. ↑ Genth H, Schmidt M, Gerhard R, Aktories K, Just I (February 2003). "Activation of phospholipase D1 by ADP-ribosylated RhoA". Biochem. Biophys. Res. Commun. 302 (1): 127–132. doi:10.1016/S0006-291X(03)00112-8. PMID 12593858. 
  8. ↑ Cai S, Exton JH (May 2001). "Determination of interaction sites of phospholipase D1 for RhoA". Biochem. J. 355 (Pt 3): 779–85. PMC 1221795. PMID 11311142. 
  9. ↑ Thodeti CK, Massoumi R, Bindslev L, Sjölander A (July 2002). "Leukotriene D4 induces association of active RhoA with phospholipase C-gamma1 in intestinal epithelial cells". Biochem. J. 365 (Pt 1): 157–63. doi:10.1042/BJ20020248. PMC 1222665. PMID 12071848. 
  10. ↑ Wennerberg K, Forget MA, Ellerbroek SM, Arthur WT, Burridge K, Settleman J, Der CJ, Hansen SH (July 2003). "Rnd proteins function as RhoA antagonists by activating p190 RhoGAP". Curr. Biol. 13 (13): 1106–1115. doi:10.1016/S0960-9822(03)00418-4. PMID 12842009. 
  11. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514. 
  12. ↑ Zhang B, Zheng Y (April 1998). "Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and 3BP-1". Biochemistry 37 (15): 5249–5257. doi:10.1021/bi9718447. PMID 9548756. 
  13. ↑ Li R, Zhang B, Zheng Y (December 1997). "Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190". J. Biol. Chem. 272 (52): 32830–32835. doi:10.1074/jbc.272.52.32830. PMID 9407060. 
  14. ↑ Zhang B, Chernoff J, Zheng Y (April 1998). "Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA". J. Biol. Chem. 273 (15): 8776–8782. doi:10.1074/jbc.273.15.8776. PMID 9535855. 
  15. ↑ 15.0 15.1 Mehta D, Ahmmed GU, Paria BC, Holinstat M, Voyno-Yasenetskaya T, Tiruppathi C, Minshall RD, Malik AB (August 2003). "RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability". J. Biol. Chem. 278 (35): 33492–33500. doi:10.1074/jbc.M302401200. PMID 12766172. 
  16. ↑ 16.0 16.1 16.2 16.3 Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Mol. Cell. Biol. 23 (12): 4219–4229. doi:10.1128/MCB.23.12.4219-4229.2003. PMC 156133. PMID 12773565. 
  17. ↑ Lutz S, Freichel-Blomquist A, Rümenapp U, Schmidt M, Jakobs KH, Wieland T (May 2004). "p63RhoGEF and GEFT are Rho-specific guanine nucleotide exchange factors encoded by the same gene". Naunyn Schmiedebergs Arch. Pharmacol. 369 (5): 540–546. doi:10.1007/s00210-004-0926-5. PMID 15069594. 
  18. ↑ Arthur WT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K (November 2002). "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC". J. Biol. Chem. 277 (45): 42964–42972. doi:10.1074/jbc.M207401200. PMID 12221096. 
  19. ↑ Suzuki N, Nakamura S, Mano H, Kozasa T (January 2003). "Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF". Proc. Natl. Acad. Sci. U.S.A. 100 (2): 733–738. doi:10.1073/pnas.0234057100. PMC 141065. PMID 12515866. 
  20. ↑ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. 
  21. ↑ Gajate C, Mollinedo F (March 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–11647. doi:10.1074/jbc.M411781200. PMID 15659383. 
  22. ↑ Michaelson D, Silletti J, Murphy G, D'Eustachio P, Rush M, Philips MR (January 2001). "Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding". J. Cell Biol. 152 (1): 111–126. doi:10.1083/jcb.152.1.111. PMC 2193662. PMID 11149925. 
  23. ↑ Gorvel JP, Chang TC, Boretto J, Azuma T, Chavrier P (January 1998). "Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity". FEBS Lett. 422 (2): 269–273. doi:10.1016/S0014-5793(98)00020-9. PMID 9490022. 
  24. ↑ Fauré J, Dagher MC (May 2001). "Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI)". Biochimie 83 (5): 409–414. doi:10.1016/S0300-9084(01)01263-9. PMID 11368848. 
  25. ↑ Cachero TG, Morielli AD, Peralta EG (June 1998). "The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel". Cell 93 (6): 1077–1085. doi:10.1016/S0092-8674(00)81212-X. PMID 9635436. 
  26. ↑ Vikis HG, Stewart S, Guan KL (April 2002). "SmgGDS displays differential binding and exchange activity towards different Ras isoforms". Oncogene 21 (15): 2425–2432. doi:10.1038/sj.onc.1205306. PMID 11948427. 
  27. ↑ Houssa B, de Widt J, Kranenburg O, Moolenaar WH, van Blitterswijk WJ (March 1999). "Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA". J. Biol. Chem. 274 (11): 6820–6822. doi:10.1074/jbc.274.11.6820. PMID 10066731. 
  28. ↑ Medley QG, Serra-Pagès C, Iannotti E, Seipel K, Tang M, O'Brien SP, Streuli M (November 2000). "The trio guanine nucleotide exchange factor is a RhoA target. Binding of RhoA to the trio immunoglobulin-like domain". J. Biol. Chem. 275 (46): 36116–36123. doi:10.1074/jbc.M003775200. PMID 10948190. 
  29. ↑ Leung T, Chen XQ, Manser E, Lim L (October 1996). "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton". Mol. Cell. Biol. 16 (10): 5313–27. PMC 231530. PMID 8816443. 
  30. ↑ Fujisawa K, Fujita A, Ishizaki T, Saito Y, Narumiya S (September 1996). "Identification of the Rho-binding domain of p160ROCK, a Rho-associated coiled-coil containing protein kinase". J. Biol. Chem. 271 (38): 23022–23028. doi:10.1074/jbc.271.38.23022. PMID 8798490. 
  31. ↑ Rümenapp U, Blomquist A, Schwörer G, Schablowski H, Psoma A, Jakobs KH (October 1999). "Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member". FEBS Lett. 459 (3): 313–318. doi:10.1016/S0014-5793(99)01270-3. PMID 10526156. 
  32. ↑ Nakazawa T, Watabe AM, Tezuka T, Yoshida Y, Yokoyama K, Umemori H, Inoue A, Okabe S, Manabe T, Yamamoto T (July 2003). "p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling". Mol. Biol. Cell 14 (7): 2921–2934. doi:10.1091/mbc.E02-09-0623. PMC 165687. PMID 12857875. 
  33. ↑ 33.0 33.1 Nakamura, Takeshi; Komiya Misako, Sone Kiyoaki, Hirose Eiji, Gotoh Noriko, Morii Hiroshi, Ohta Yasutaka, Mori Nozomu (December 2002). "Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules". Mol. Cell. Biol. (United States) 22 (24): 8721–8734. doi:10.1128/MCB.22.24.8721-8734.2002. ISSN 0270-7306. PMC 139861. PMID 12446789. 
  34. ↑ Quilliam LA, Lambert QT, Mickelson-Young LA, Westwick JK, Sparks AB, Kay BK, Jenkins NA, Gilbert DJ, Copeland NG, Der CJ (November 1996). "Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling". J. Biol. Chem. 271 (46): 28772–28776. doi:10.1074/jbc.271.46.28772. PMID 8910519. 
  35. ↑ 35.0 35.1 Flynn P, Mellor H, Palmer R, Panayotou G, Parker PJ (January 1998). "Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif". J. Biol. Chem. 273 (5): 2698–2705. doi:10.1074/jbc.273.5.2698. PMID 9446575. 
  36. ↑ Gebbink MF, Kranenburg O, Poland M, van Horck FP, Houssa B, Moolenaar WH (June 1997). "Identification of a novel, putative Rho-specific GDP/GTP exchange factor and a RhoA-binding protein: control of neuronal morphology". J. Cell Biol. 137 (7): 1603–1613. doi:10.1083/jcb.137.7.1603. PMC 2137826. PMID 9199174. 
  37. ↑ Alberts AS, Bouquin N, Johnston LH, Treisman R (April 1998). "Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the yeast response regulator protein Skn7". J. Biol. Chem. 273 (15): 8616–8622. doi:10.1074/jbc.273.15.8616. PMID 9535835. 
  38. ↑ Madaule P, Furuyashiki T, Reid T, Ishizaki T, Watanabe G, Morii N, Narumiya S (December 1995). "A novel partner for the GTP-bound forms of rho and rac". FEBS Lett. 377 (2): 243–248. doi:10.1016/0014-5793(95)01351-2. PMID 8543060. 
  39. ↑ Neudauer CL, Joberty G, Macara IG (January 2001). "PIST: a novel PDZ/coiled-coil domain binding partner for the rho-family GTPase TC10". Biochem. Biophys. Res. Commun. 280 (2): 541–547. doi:10.1006/bbrc.2000.4160. PMID 11162552. 
  40. ↑ Hotta K, Tanaka K, Mino A, Kohno H, Takai Y (August 1996). "Interaction of the Rho family small G proteins with kinectin, an anchoring protein of kinesin motor". Biochem. Biophys. Res. Commun. 225 (1): 69–74. doi:10.1006/bbrc.1996.1132. PMID 8769096. 
  41. ↑ Vignal E, Blangy A, Martin M, Gauthier-Rouvière C, Fort P (December 2001). "Kinectin is a key effector of RhoG microtubule-dependent cellular activity". Mol. Cell. Biol. 21 (23): 8022–8034. doi:10.1128/MCB.21.23.8022-8034.2001. PMC 99969. PMID 11689693. 

Further reading

External links

3.6.1
3.6.2
3.6.3-4: ATPase
3.6.3
Cu++ (3.6.3.4)
Ca+ (3.6.3.8)
Na+/K+ (3.6.3.9)
H+/K+ (3.6.3.10)
  • ATP4A
Other P-type ATPase
3.6.4
3.6.5: GTPase
3.6.5.1: Heterotrimeric G protein
3.6.5.2: Small GTPase > Ras superfamily
3.6.5.3: Protein-synthesizing GTPase
3.6.5.5-6: Polymerization motors
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3.6.1
3.6.2
3.6.3-4: ATPase
3.6.3
Cu++ (3.6.3.4)
Ca+ (3.6.3.8)
Na+/K+ (3.6.3.9)
H+/K+ (3.6.3.10)
  • ATP4A
Other P-type ATPase
3.6.4
3.6.5: GTPase
3.6.5.1: Heterotrimeric G protein
3.6.5.2: Small GTPase > Ras superfamily
3.6.5.3: Protein-synthesizing GTPase
3.6.5.5-6: Polymerization motors
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