FMNL1 binds RAC1:GTP

Stable Identifier
Reaction [binding]
Homo sapiens
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FMNL1 (formin-like protein 1) binds the active, GTP-bound, form of RAC1 (Yayoshi-Yamamoto et al. 2000). Based on the sequence similarity with mouse formin Dia1, binding of RAC1:GTP relieves the autoinhibition of FMNL1 by displacing the C-terminal autoregulatory DAD domain of FMNL1 from the N-terminal FH3 domain (Rose et al. 2005, Lammers et al. 2005). As formins dimerize through their FH2 domains, it is not clear whether the autoinhibitory interaction between FH3 and DAD domains is intramolecular or intermolecular (Xu et al. 2004, Kuhn and Geyer 2014). Endogenous human FMNL1 interacts with endogenous human RAC1 in some leukemia-derived cell lines and promotes their migration (Favaro et al. 2013). FMNL1 gamma, a transcriptional isoform of FMNL1 with a DAD domain that significantly differs in sequence from DAD domains of FMNL1 transcription isoforms alpha and beta, localizes to the membrane and is active in the absence of RHO GTPase signaling. The membrane localization of FMNL1 gamma is regulated by the myristoylation of the N-terminal glycine which is triggered by an unknown mechanism (Han et al. 2009).

Literature References
PubMed ID Title Journal Year
15864301 Structural and mechanistic insights into the interaction between Rho and mammalian Dia

Rose, R, Weyand, M, Lammers, M, Ishizaki, T, Ahmadian, MR, Wittinghofer, A

Nature 2005
23801653 FMNL1 promotes proliferation and migration of leukemia cells

Favaro, P, Traina, F, Machado-Neto, JA, Lazarini, M, Lopes, MR, Pereira, JK, Costa, FF, Infante, E, Ridley, AJ, Saad, ST

J. Leukoc. Biol. 2013
15006353 Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture

Xu, Y, Moseley, JB, Sagot, I, Poy, F, Pellman, D, Goode, BL, Eck, MJ

Cell 2004
24914801 Formins as effector proteins of Rho GTPases

Kühn, S, Geyer, M

Small GTPases 2014
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
19815554 Formin-like 1 (FMNL1) is regulated by N-terminal myristoylation and induces polarized membrane blebbing

Han, Y, Eppinger, E, Schuster, IG, Weigand, LU, Liang, X, Kremmer, E, Peschel, C, Krackhardt, AM

J. Biol. Chem. 2009
16292343 The regulation of mDia1 by autoinhibition and its release by Rho*GTP

Lammers, M, Rose, R, Scrima, A, Wittinghofer, A

EMBO J. 2005
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