RAC1 binds effectors at the plasma membrane

Stable Identifier
R-HSA-9013145
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
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In its GTP bound active form, plasma membrane associated RAC1 binds to the following cytosolic and plasma membrane effectors:
BAIAP2 (Lewis Saravalli et al. 2013, Bagci et al. 2020)
CAV1 (Nethe et al. 2010, Bagci et al. 2020)
CDC42BPA (Schwarz et al. 2012)
CIT (Madaule et al. 1995)
CIT 3 (Di Cunto et al. 1998)
CYFIP1 (Schneck et al. 2003, Bagci et al. 2020)
FMNL1 (Yayoshi Yamamoto et al. 2000)
IQGAP1 (Kuroda et al. 1996, Pelikan Conchaudron et al. 2011)
IQGAP2 (Brill et al. 1996, Ozdemir et al. 2018)
IQGAP3 (Wang et al. 2007)
KIAA0355 (Bagci et al. 2020: interaction studied in detail)
NISCH (Reddig et al. 2005)
NOX1 complex (Cheng et al. 2006, Miyano et al. 2006, Kao et al. 2008)
NOX2 complex (Ushio Fukai et al. 2002)
NOX3 complex (Ueyama et al. 2006, Miyano and Sumimoto 2007, Kao et al. 2008)
PAK1 (Parrini et al. 2002)
PAK2 (Manser et al. 1994, Manser et al. 1995, Bagci et al. 2020)
PAK3 (Manser et al. 1995)
PAK4 (Abo et al. 1998, Bagci et al. 2020)
PAK5 (Dan et al. 2002)
PAK6 (Lee et al. 2002)
PARD6A (Qiu et al. 2000)
PI3K alpha (Bokoch et at al. 1996, Murga et al. 2002)
PKN1 (Owen et al. 2003, Modha et al. 2008)
PKN2 (Zong et al. 1999)
PLD1 (Hammond et al. 1997)
PLD2 (Hiroyama and Exton 2005)
WAVE complex (Miki et al. 1998, Suetsugu et al. 2006, Bagci et al. 2020)

The following RAC1 effectors are annotated as candidate effectors either because of opposing finding reported in different studies or because they have only been reported in the high throughput screen by Bagci et al. 2020:
ABI1 (Bagci et al. 2020)
ABL2 (Bagci et al. 2020)
AMIGO2 (Bagci et al. 2020)
ARAP2 (Bagci et al. 2020)
BAIAP2L1 (Bagci et al. 2020)
BRK1 (Bagci et al. 2020)
CDC42 (Bagci et al. 2020)
CDC42EP1 (Bagci et al. 2020: binding to activated RAC1; Joberty et al. 1999: no binding to activated RAC1)
CDC42EP4 (Bagci et al. 2020: binding to activated RAC1; Joberty et al. 1999: no binding to activated RAC1)
DEPDC1B (Bagci et al. 2020)
DIAPH3 (Bagci et al. 2020)
EPHA2 (Bagci et al. 2020)
ERBIN (Bagci et al. 2020)
FERMT2 (Bagci et al. 2020)
GIT1 (Bagci et al. 2020)
GIT2 (Bagci et al. 2020)
ITGB1 (Bagci et al. 2020)
JAG1 (Bagci et al. 2020)
LAMTOR1 (Bagci et al. 2020)
MCAM (Bagci et al. 2020)
MPP7 (Bagci et al. 2020)
NCKAP1 (Bagci et al. 2020)
NHS (Bagci et al. 2020)
PLEKHG3 (Bagci et al. 2020)
PLEKHG4 (Bagci et al. 2020)
RAB7A (Bagci et al. 2020)
SLC1A5 (Bagci et al. 2020)
SNAP23 (Bagci et al. 2020)
SWAP70 (Bagci et al. 2020)
TAOK3 (Bagci et al. 2020)
TFRC (Bagci et al. 2020)
TMPO (Bagci et al. 2020)
VAMP3 (Bagci et al. 2020)
VANGL1 (Bagci et al. 2020)
WIP WASP complex (WAS, also known as WASP, a component of the WIP WASP complex, was reported to interact with active RAC1 by Aspenstrom et al. 1996 and Vastrik et al. 1999, but no interaction has been reported between RAC1 and WIP components of the complex, WIPF1, WIPF2 or WIPF3)

Active RAC1 does not bind the following RHO GTPase effectors:
ANKLE2 (Bagci et al. 2020)
ARFGAP3 (Bagci et al. 2020)
ARMCX3 (Bagci et al. 2020)
CDC42EP2 (Joberty et al. 1999)
CDC42EP3 (Joberty et al. 1999)
CDC42EP5 (Joberty et al. 1999)
DSG2 (Bagci et al. 2020)
DIAPH1 (Higashi et al. 2008)
DOCK1 (Bagci et al. 2020)
DOCK5 (Bagci et al. 2020)
ELMO2 (Bagci et al. 2020)
FMNL2 (Block et al. 2012)
HSPE1 (Bagci et al. 2020)
IL32 (Bagci et al. 2020)
LETM1 (Bagci et al. 2020)
LMAN1 (Bagci et al. 2020)
NDUFA5 (Bagci et al. 2020)
NDUFS3 (Bagci et al. 2020)
PGRMC2 (Bagci et al. 2020)
RAPGEF1 (Bagci et al. 2020)
ROCK1 (Leung et al. 1996)
ROCK2 (Leung et al. 1996)
RTKN (Reid et al. 1996)
SHMT2 (Bagci et al. 2020)
SLK (Yamada et al. 2000)
SLITRK3 (Bagci et al. 2020)
SLITRK5 (Bagci et al. 2020)
STBD1 (Bagci et al. 2020)
STX5 (Bagci et al. 2020)
VAPB (Bagci et al. 2020)

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

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
7559638 Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family

Manser, E, Chong, C, Zhao, ZS, Leung, T, Michael, G, Hall, C, Lim, L

J. Biol. Chem. 1995
10508610 Sema3A-induced growth-cone collapse is mediated by Rac1 amino acids 17-32

Västrik, I, Eickholt, BJ, Walsh, FS, Ridley, A, Doherty, P

Curr. Biol. 1999
16702231 Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP(3), and Rac

Suetsugu, S, Kurisu, S, Oikawa, T, Yamazaki, D, Oda, A, Takenawa, T

J Cell Biol 2006
11756552 PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells

Dan, C, Nath, N, Liberto, M, Minden, A

Mol. Cell. Biol. 2002
21730051 The IQGAP1 protein is a calmodulin-regulated barbed end capper of actin filaments: possible implications in its function in cell migration

Pelikan-Conchaudron, A, Le Clainche, C, Didry, D, Carlier, MF

J. Biol. Chem. 2011
9843499 WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac

Miki, H, Suetsugu, S, Takenawa, T

EMBO J 1998
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
16762923 Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1

Miyano, K, Ueno, N, Takeya, R, Sumimoto, H

J. Biol. Chem. 2006
10699464 Molecular cloning and characterization of a novel human STE20-like kinase, hSLK

Yamada, E, Tsujikawa, K, Itoh, S, Kameda, Y, Kohama, Y, Yamamoto, H

Biochim. Biophys. Acta 2000
23707487 ARF1 controls Rac1 signaling to regulate migration of MDA-MB-231 invasive breast cancer cells

Lewis-Saravalli, S, Campbell, S, Claing, A

Cell. Signal. 2013
17583407 Role of the small GTPase Rac in p22phox-dependent NADPH oxidases

Miyano, K, Sumimoto, H

Biochimie 2007
10958683 FRL, a novel formin-related protein, binds to Rac and regulates cell motility and survival of macrophages

Yayoshi-Yamamoto, S, Taniuchi, I, Watanabe, T

Mol. Cell. Biol. 2000
18347018 Identification of a conserved Rac-binding site on NADPH oxidases supports a direct GTPase regulatory mechanism

Kao, YY, Gianni, D, Bohl, B, Taylor, RM, Bokoch, GM

J. Biol. Chem. 2008
16002401 Regulation of p21-activated kinase-independent Rac1 signal transduction by nischarin

Reddig, PJ, Xu, D, Juliano, RL

J. Biol. Chem. 2005
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
22608513 FMNL2 drives actin-based protrusion and migration downstream of Cdc42

Block, J, Breitsprecher, D, Kühn, S, Winterhoff, M, Kage, F, Geffers, R, Duwe, P, Rohn, JL, Baum, B, Brakebusch, C, Geyer, M, Stradal, TE, Faix, J, Rottner, K

Curr. Biol. 2012
12480817 Novel role of gp91(phox)-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis

Ushio-Fukai, M, Tang, Y, Fukai, T, Dikalov, SI, Ma, Y, Fujimoto, M, Quinn, MT, Pagano, PJ, Johnson, C, Alexander, RW

Circ. Res. 2002
8798539 Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1

Kuroda, S, Fukata, M, Kobayashi, K, Nakafuku, M, Nomura, N, Iwamatsu, A, Kaibuchi, K

J. Biol. Chem. 1996
22970203 Serine-71 phosphorylation of Rac1 modulates downstream signaling

Schwarz, J, Proff, J, Hävemeier, A, Ladwein, M, Rottner, K, Barlag, B, Pich, A, Tatge, H, Just, I, Gerhard, R

PLoS ONE 2012
11773441 AR and ER interaction with a p21-activated kinase (PAK6)

Lee, SR, Ramos, SM, Ko, A, Masiello, D, Swanson, KD, Lu, ML, Balk, SP

Mol. Endocrinol. 2002
8805223 Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome

Aspenström, P, Lindberg, U, Hall, A

Curr Biol 1996
11803464 Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-kappaB

Murga, C, Zohar, M, Teramoto, H, Gutkind, JS

Oncogene 2002
10490598 The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins

Joberty, G, Perlungher, RR, Macara, IG

Mol. Cell. Biol. 1999
8107774 A brain serine/threonine protein kinase activated by Cdc42 and Rac1

Manser, E, Leung, T, Salihuddin, H, Zhao, ZS, Lim, L

Nature 1994
18006505 The Rac1 polybasic region is required for interaction with its effector PRK1

Modha, R, Campbell, LJ, Nietlispach, D, Buhecha, HR, Owen, D, Mott, HR

J. Biol. Chem. 2008
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
9988689 Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation

Zong, H, Raman, N, Mickelson-Young, LA, Atkinson, SJ, Quilliam, LA

J. Biol. Chem. 1999
8645157 Rac GTPase interacts specifically with phosphatidylinositol 3-kinase

Bokoch, GM, Vlahos, CJ, Wang, Y, Knaus, UG, Traynor-Kaplan, AE

Biochem J 1996
29358323 Unraveling the molecular mechanism of interactions of the Rho GTPases Cdc42 and Rac1 with the scaffolding protein IQGAP2

Ozdemir, ES, Jang, H, Gursoy, A, Keskin, O, Li, Z, Sacks, DB, Nussinov, R

J. Biol. Chem. 2018
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
16507994 Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases

Ueyama, T, Geiszt, M, Leto, TL

Mol. Cell. Biol. 2006
17244649 IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth

Wang, S, Watanabe, T, Noritake, J, Fukata, M, Yoshimura, T, Itoh, N, Harada, T, Nakagawa, M, Matsuura, Y, Arimura, N, Kaibuchi, K

J. Cell. Sci. 2007
14514689 Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1)

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J. Biol. Chem. 2003
9822598 PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia

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11804587 Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1

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Mol Cell 2002
20460433 Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway

Nethe, M, Anthony, EC, Fernandez-Borja, M, Dee, R, Geerts, D, Hensbergen, PJ, Deelder, AM, Schmidt, G, Hordijk, PL

J. Cell. Sci. 2010
8543060 A novel partner for the GTP-bound forms of rho and rac

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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

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Mol. Cell. Biol. 1996
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J. Biol. Chem. 2006
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