Reactome | RHOA binds effectors at the plasma membrane

RHOA binds effectors at the plasma membrane

Stable Identifier

R-HSA-9013009

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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RHOA binds effectors at the plasma membrane

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In its GTP bound active form, plasma membrane associated RHOA (or constitutively active RHOA mutant in the high throughput study by Bagci et al. 2020) binds to the following effectors:
ANLN (Piekny and Glotzer 2008; Budnar et al. 2019; Bagci et al. 2020)
CIT (Madaule et al. 1995; Bagci et al. 2020) and its neuron specific splicing isoform CIT 3 (Di Cunto et al. 1998)
DAAM1 (Aspenstrom et al. 2006; Higashi et al. 2008)
DIAPH1 (Otomo et al. 2005; Higashi et al. 2008; Lammers et al. 2008; Gao et al. 2009; Li and Sewer 2010; Bagci et al. 2020)
DIAPH3 (Alberts et al. 1998; Watanabe et al. 2010; Staus et al. 2011; Chen et al. 2017; Bagci et al. 2020)
IQGAP1 (Casteel et al. 2012)
PKN1 (Maesaki et al. 1999; Hutchinson et al. 2011; Hutchinson et al. 2013)
PKN2 (Hutchinson et al. 2013; Bagci et al. 2020)
PKN3 (Hutchinson et al. 2013)
PLD1 (Hammond et al. 1997; Yamazaki et al. 1999)
RHPN1 (Watanabe et al. 1996; Peck et al. 2002)
RHPN2 (Peck et al. 2002)
ROCK1 (Ishizaki et al. 1996; Leung et al. 1996; Bagci et al. 2020)
ROCK2 (Leung et al. 1996; Bagci et al. 2020)
RTKN (Reid et al. 1996; Fu et al. 2000)
SLK (Bagci et al. 2020: interaction and activation of SLK downstream of RHOA confirmed in detail)
STK10 (Bagci et al. 2020: interaction corroborated by additional experimental methods)

The following putative RHOA effectors are annotated as candidates either because of opposing findings reported by different studies or because their binding to RHOA was only shown in the context of constitutively active RHOA mutant in the high throughput screen by Bagci et al. 2020:
AAAS (Bagci et al. 2020)
ABCD3 (Bagci et al. 2020)
ACBD5 (Bagci et al. 2020)
ACTC1 (Bagci et al. 2020)
ARHGAP1 (Bagci et al. 2020)
BCR (Bagci et al. 2020)
C1QBP (Bagci et al. 2020)
CAV1 (Bagci et al. 2020)
CAVIN1 (Bagci et al. 2020)
DEPDC1B (Bagci et al. 2020)
ERBIN (Bagci et al. 2020)
FAF2 (Bagci et al. 2020)
FLOT1 (Bagci et al. 2020)
FLOT2 (Bagci et al. 2020)
FMNL3 (Bagci et al. 2020: binding to RHOA; Vega et al. 2011: no binding to RHOA)
HMOX2 (Bagci et al. 2020)
IQGAP3 (Bagci et al. 2020)
JUP (Bagci et al. 2020)
MCAM (Bagci et al. 2020)
MYO9B (Bagci et al. 2020)
PCDH7 (Bagci et al. 2020)
SCFD1 (Bagci et al. 2020)
SNAP23 (Bagci et al. 2020)
SOWAHC (Bagci et al. 2020)
STBD1 (Bagci et al. 2020)
STOM (Bagci et al. 2020)
TFRC (Bagci et al. 2020)
TJP2 (Bagci et al. 2020)
TMPO (Bagci et al. 2020)
VAMP3 (Bagci et al. 2020)
VANGL1 (Bagci et al. 2020)

RHOA does not bind the following effectors:
CCDC187 (Bagci et al. 2020)
CDC42BPA (Leung et al. 1998)
CDC42BPB (Leung et al. 1998)
CDC42EP1 (Joberty et al. 1999)
CDC42EP2 (Joberty et al. 1999)
CDC42EP3 (Joberty et al. 1999)
CDC42EP4 (Joberty et al. 1999)
CDC42EP5 (Joberty et al. 1999)
FMNL2 (Kitzing et al. 2010)
IQGAP2 (Brill et al. 1996)
KIAA0355 (Bagci et al. 2020)
PLD2 (Kodaki and Yamashita 1997)
WAS (WASP) (Aspenstrom et al. 1996)

Literature References

PubMed ID	Title	Journal	Year
18218625	Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDia1 and Daam1, in platelets Ikeda, T, Kondo, H, Horiuchi, H, Okuda, T, Okawa, K, Shirakawa, R, Higashi, T, Kita, T, Kawato, M, Nureki, O, Fukai, S, Horiguchi, M	J. Biol. Chem.	2008
8617235	The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase Saito, Y, Fujita, A, Narumiya, S, Okawa, K, Iwamatsu, A, Morii, N, Fujisawa, K, Kakizuka, A, Ishizaki, T, Watanabe, N, Maekawa, M	EMBO J	1996
10873388	Molecular cloning, expression characterization, and mapping of a novel putative inhibitor of rho GTPase activity, RTKN, to D2S145-D2S286 Yu, L, Zhang, J, Fu, Q, Zhao, S, Zhang, H, Liu, Q	Genomics	2000
8816443	The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton Lim, L, Manser, E, Leung, T, Chen, XQ	Mol. Cell. Biol.	1996
20101212	Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC Grosse, R, Copeland, JW, Kitzing, TM, Pertz, O, Wang, Y	Oncogene	2010
9535835	Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the yeast response regulator protein Skn7 Johnston, LH, Bouquin, N, Alberts, AS, Treisman, R	J. Biol. Chem.	1998
8662891	Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the rho-binding domain Madaule, P, Fujisawa, K, Narumiya, S, Furuyashiki, T, Watanabe, G, Reid, T, Watanabe, N, Ishizaki, T, Morii, N	J. Biol. Chem.	1996
10619026	The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1 Kaibuchi, K, Kuroda, S, Hakoshima, T, Shimizu, T, Ihara, K, Maesaki, R	Mol. Cell	1999
9829970	Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3 Lassam, N, Leung, IW	J Biol Chem	1998
15866170	Structural basis of Rho GTPase-mediated activation of the formin mDia1 Rosen, MK, Tomchick, DR, Machius, M, Otomo, C, Otomo, T	Mol. Cell	2005
12221077	The RhoA-binding protein, rhophilin-2, regulates actin cytoskeleton organization Bouker, KB, Burbelo, PD, Peck, JW, Oberst, M, Bowden, E	J. Biol. Chem.	2002
10490598	The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins Joberty, G, Macara, IG, Perlungher, RR	Mol. Cell. Biol.	1999
21351730	Mutational analysis reveals a single binding interface between RhoA and its effector, PRK1 Mott, HR, Owen, D, McLaughlin, SH, Hutchinson, CL, Lowe, PN	Biochemistry	2011
20030946	[PI3-kinase mediates activity of RhoA and interaction of RhoA with mDia1 in thrombin-induced platelet aggregation] Chen, XQ, Gao, Y, Gao, GX, Yang, Y, Pan, YZ, Dong, HJ, Gu, HT	Zhongguo Shi Yan Xue Ye Xue Za Zhi	2009
29146911	Cytokinesis requires localized β-actin filament production by an actin isoform specific nucleator Chen, A, McCulloch, CA, Wilde, A, Arora, PD	Nat Commun	2017
31871319	Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms Tran, V, Gingras, AC, Elkholi, IE, Robert, A, Boulais, J, Faubert, D, Dubé, N, Hipfner, DR, Cote, JF, Lin, ZY, Bagci, H, Sriskandarajah, N, Thibault, MP	Nat. Cell Biol.	2020
20660154	Rho and anillin-dependent control of mDia2 localization and function in cytokinesis Narumiya, S, Ishizaki, T, Arakawa, T, Sakamoto, S, Okawa, K, Watanabe, S, Segawa, K, Miki, T, Kinoshita, M, Morinaga, T	Mol. Biol. Cell	2010
22992742	Rho isoform-specific interaction with IQGAP1 promotes breast cancer cell proliferation and migration Su-Yuo, J, Casteel, DE, Zhuang, S, Schwappacher, R, Pilz, RB, Rangaswami, H, Turner, S, Boss, GR	J. Biol. Chem.	2012
21699497	Enhancement of mDia2 activity by Rho-kinase-dependent phosphorylation of the diaphanous autoregulatory domain Mack, CP, Taylor, JM, Staus, DP	Biochem. J.	2011
9792683	Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron Calautti, E, Turco, E, Di Cunto, F, Ong, L, Dotto, GP, Topley, G, Hsiao, J	J. Biol. Chem.	1998
24128008	Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB Mott, HR, Owen, D, McLaughlin, SH, Hutchinson, CL, Lowe, PN	Biochemistry	2013
20591975	RhoA and DIAPH1 mediate adrenocorticotropin-stimulated cortisol biosynthesis by regulating mitochondrial trafficking Li, D, Sewer, MB	Endocrinology	2010
18829452	Specificity of interactions between mDia isoforms and Rho proteins Lammers, M, Wittinghofer, A, Kühlmann, D, Meyer, S	J. Biol. Chem.	2008
8571126	Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho Madaule, P, Kakizuka, A, Mukai, H, Fujisawa, K, Narumiya, S, Watanabe, G, Ishizaki, T, Saito, Y, Morii, N, Ono, Y	Science	1996
8543060	A novel partner for the GTP-bound forms of rho and rac Madaule, P, Narumiya, S, Furuyashiki, T, Watanabe, G, Reid, T, Ishizaki, T, Morii, N	FEBS Lett.	1995
9013646	Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C-alpha Morris, AJ, Nozawa, Y, Frohman, MA, Cadwallader, K, Hammond, SM, Prestwich, GD, Cook, S, Gu, Q, Jenco, JM, Nakashima, S	J. Biol. Chem.	1997
9418861	Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization Manser, E, Leung, T, Lim, L, Tan, I, Chen, XQ	Mol Cell Biol	1998
8756646	The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases Li, S, Church, DM, Weissbach, L, Wasmuth, JJ, Lyman, CW, Snijders, AJ, Bernards, A, Brill, S	Mol. Cell. Biol.	1996
9111050	Cloning, expression, and characterization of a novel phospholipase D complementary DNA from rat brain Yamashita, S, Kodaki, T	J. Biol. Chem.	1997
31105010	Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics Yap, AS, Naghibosadat, M, Budnar, S, Verma, S, Husain, KB, Morris, RG, Gomez, GA, Varma, A, Hamilton, NA	Dev. Cell	2019
10037681	Interaction of the small G protein RhoA with the C terminus of human phospholipase D1 Zhang, Y, Shibata, H, Kanaho, Y, Watanabe, H, Kaibuchi, K, Ohno, S, Mukai, H, Yamazaki, M, Frohman, MA, Ono, Y, Yokozeki, T	J. Biol. Chem.	1999
16630611	The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics Richnau, N, Johansson, AS, Aspenström, P	Exp. Cell Res.	2006
18158243	Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis Glotzer, M, Piekny, AJ	Curr. Biol.	2008