RHOA binds effectors at the plasma membrane

Stable Identifier
R-HSA-9013009
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
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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
8617235 The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase

Ishizaki, T, Maekawa, M, Fujisawa, K, Okawa, K, Iwamatsu, A, Fujita, A, Watanabe, N, Saito, Y, Kakizuka, A, Morii, N, Narumiya, S

EMBO J 1996
18218625 Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDia1 and Daam1, in platelets

Higashi, T, Ikeda, T, Shirakawa, R, Kondo, H, Kawato, M, Horiguchi, M, Okuda, T, Okawa, K, Fukai, S, Nureki, O, Kita, T, Horiuchi, H

J. Biol. Chem. 2008
10873388 Molecular cloning, expression characterization, and mapping of a novel putative inhibitor of rho GTPase activity, RTKN, to D2S145-D2S286

Fu, Q, Yu, L, Liu, Q, Zhang, J, Zhang, H, Zhao, S

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

Leung, T, Chen, XQ, Manser, E, Lim, L

Mol. Cell. Biol. 1996
20101212 Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC

Kitzing, TM, Wang, Y, Pertz, O, Copeland, JW, Grosse, R

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

Alberts, AS, Bouquin, N, Johnston, LH, 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

Reid, T, Furuyashiki, T, Ishizaki, T, Watanabe, G, Watanabe, N, Fujisawa, K, Morii, N, Madaule, P, Narumiya, S

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

Maesaki, R, Ihara, K, Shimizu, T, Kuroda, S, Kaibuchi, K, Hakoshima, T

Mol. Cell 1999
9829970 Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3

Leung, IW, Lassam, N

J Biol Chem 1998
15866170 Structural basis of Rho GTPase-mediated activation of the formin mDia1

Otomo, T, Otomo, C, Tomchick, DR, Machius, M, Rosen, MK

Mol. Cell 2005
12221077 The RhoA-binding protein, rhophilin-2, regulates actin cytoskeleton organization

Peck, JW, Oberst, M, Bouker, KB, Bowden, E, Burbelo, PD

J. Biol. Chem. 2002
10490598 The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins

Joberty, G, Perlungher, RR, Macara, IG

Mol. Cell. Biol. 1999
21351730 Mutational analysis reveals a single binding interface between RhoA and its effector, PRK1

Hutchinson, CL, Lowe, PN, McLaughlin, SH, Mott, HR, Owen, D

Biochemistry 2011
20030946 [PI3-kinase mediates activity of RhoA and interaction of RhoA with mDia1 in thrombin-induced platelet aggregation]

Gao, GX, Dong, HJ, Gu, HT, Gao, Y, Pan, YZ, Yang, Y, Chen, XQ

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, Arora, PD, McCulloch, CA, Wilde, A

Nat Commun 2017
31871319 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms

Bagci, H, Sriskandarajah, N, Robert, A, Boulais, J, Elkholi, IE, Tran, V, Lin, ZY, Thibault, MP, Dubé, N, Faubert, D, Hipfner, DR, Gingras, AC, Cote, JF

Nat. Cell Biol. 2020
20660154 Rho and anillin-dependent control of mDia2 localization and function in cytokinesis

Watanabe, S, Okawa, K, Miki, T, Sakamoto, S, Morinaga, T, Segawa, K, Arakawa, T, Kinoshita, M, Ishizaki, T, Narumiya, S

Mol. Biol. Cell 2010
22992742 Rho isoform-specific interaction with IQGAP1 promotes breast cancer cell proliferation and migration

Casteel, DE, Turner, S, Schwappacher, R, Rangaswami, H, Su-Yuo, J, Zhuang, S, Boss, GR, Pilz, RB

J. Biol. Chem. 2012
21699497 Enhancement of mDia2 activity by Rho-kinase-dependent phosphorylation of the diaphanous autoregulatory domain

Staus, DP, Taylor, JM, Mack, CP

Biochem. J. 2011
9792683 Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron

Di Cunto, F, Calautti, E, Hsiao, J, Ong, L, Topley, G, Turco, E, Dotto, GP

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

Hutchinson, CL, Lowe, PN, McLaughlin, SH, Mott, HR, Owen, D

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, Meyer, S, Kühlmann, D, Wittinghofer, A

J. Biol. Chem. 2008
8571126 Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho

Watanabe, G, Saito, Y, Madaule, P, Ishizaki, T, Fujisawa, K, Morii, N, Mukai, H, Ono, Y, Kakizuka, A, Narumiya, S

Science 1996
8543060 A novel partner for the GTP-bound forms of rho and rac

Madaule, P, Furuyashiki, T, Reid, T, Ishizaki, T, Watanabe, G, Morii, N, Narumiya, S

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

Hammond, SM, Jenco, JM, Nakashima, S, Cadwallader, K, Gu, Q, Cook, S, Nozawa, Y, Prestwich, GD, Frohman, MA, Morris, AJ

J. Biol. Chem. 1997
9418861 Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization

Leung, T, Chen, XQ, Tan, I, Manser, E, Lim, L

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

Brill, S, Li, S, Lyman, CW, Church, DM, Wasmuth, JJ, Weissbach, L, Bernards, A, Snijders, AJ

Mol. Cell. Biol. 1996
9111050 Cloning, expression, and characterization of a novel phospholipase D complementary DNA from rat brain

Kodaki, T, Yamashita, S

J. Biol. Chem. 1997
31105010 Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics

Budnar, S, Husain, KB, Gomez, GA, Naghibosadat, M, Varma, A, Verma, S, Hamilton, NA, Morris, RG, Yap, AS

Dev. Cell 2019
10037681 Interaction of the small G protein RhoA with the C terminus of human phospholipase D1

Yamazaki, M, Zhang, Y, Watanabe, H, Yokozeki, T, Ohno, S, Kaibuchi, K, Shibata, H, Mukai, H, Ono, Y, Frohman, MA, Kanaho, Y

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

Aspenström, P, Richnau, N, Johansson, AS

Exp. Cell Res. 2006
18158243 Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis

Piekny, AJ, Glotzer, M

Curr. Biol. 2008
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