{PDOC51231} {PS51231; DAD} {BEGIN} ************************************************** * Diaphanous autoregulatory domain (DAD) profile * ************************************************** Formins participate in the assembly of the actin and microtubule cytoskeletons in processes like cell division, migration, and development. Diaphanous-related formins (DRF) contain an N-terminal GTPase-binding domain (GBD) and a C-terminal diaphanous autoregulatory domain (DAD). DRFs are regulated by an autoinhibitory interaction of the C-terminal DAD with the DRF N-terminal armadillo repeat-like region (see ) in the DID or GBD/FH3 domain [1-3]. This autoinhibition is released upon competitive binding of an activated Rho GTPase to the GBD. The release of DAD allows the catalytical formin homology 2 (FH2) domain to then nucleate and elongate nonbranched actin filaments. The DAD domain is a ~32 amino acid autoinhibitory domain, which facilitates intramolecular binding. The DAD core forms an alpha-helical structure (see ) [3, 4] and the C-terminal part of the domain contains several basic residues that form a basic region [5, 6]. Some proteins known to contain a DAD domain: - Fruit fly protein diaphanous, which plays an important role during cytokinesis. - Mammalian diaphanous-related formins (DRF) 1-3, which act as Rho GTPase effectors during cytoskeletal remodeling. - Baker's yeast proteins BNI1 and BNI1-related protein 1 (BNR1). - Aspergillus nidulans cytokinesis protein sepA, which participates in two actin-mediated processes, septum formation and polarized growth. - Mammalian disheveled-associated activator of morphogenesis (DAAM) proteins. - Mammalian formin-like 1 protein (Fmnl1) or formin-related protein gene in leukocytes (FRL). The profile we developed covers the entire DAD domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: July 2006 / First entry. [ 1] Higgs H.N. "Formin proteins: a domain-based approach." Trends Biochem. Sci. 30:342-353(2005). PubMed=15950879; DOI=10.1016/j.tibs.2005.04.014 [ 2] Rivero F., Muramoto T., Meyer A.-K., Urushihara H., Uyeda T.Q.P., Kitayama C. "A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa." BMC Genomics 6:28-28(2005). PubMed=15740615; DOI=10.1186/1471-2164-6-28 [ 3] Lammers M., Rose R., Scrima A., Wittinghofer A. "The regulation of mDia1 by autoinhibition and its release by Rho*GTP." EMBO J. 24:4176-4187(2005). PubMed=16292343; DOI=10.1038/sj.emboj.7600879 [ 4] Nezami A.G., Poy F., Eck M.J. "Structure of the autoinhibitory switch in formin mDia1." Structure 14:257-263(2006). PubMed=16472745; DOI=10.1016/j.str.2005.12.003 [ 5] Alberts A.S. "Identification of a carboxyl-terminal diaphanous-related formin homology protein autoregulatory domain." J. Biol. Chem. 276:2824-2830(2001). PubMed=11035012; DOI=10.1074/jbc.M006205200 [ 6] Wallar B.J., Stropich B.N., Schoenherr J.A., Holman H.A., Kitchen S.M., Alberts A.S. "The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the diaphanous-related formin inhibitory domain." J. Biol. Chem. 281:4300-4307(2006). PubMed=16361707; DOI=10.1074/jbc.M510277200 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}