PROSITE documentation PDOC51231Diaphanous 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 <PDOC50176>) in the DID or GBD/FH3 domain [1,2,3]. 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 α-helical structure (see <PDB:2BAP; D>) [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.
Last update:July 2006 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Higgs H.N. |
| Title | Formin proteins: a domain-based approach. | |
| Source | Trends Biochem. Sci. 30:342-353(2005). | |
| PubMed ID | 15950879 | |
| DOI | 10.1016/j.tibs.2005.04.014 |
| 2 | Authors | Rivero F. Muramoto T. Meyer A.-K. Urushihara H. Uyeda T.Q.P. Kitayama C. |
| Title | A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa. | |
| Source | BMC Genomics 6:28-28(2005). | |
| PubMed ID | 15740615 | |
| DOI | 10.1186/1471-2164-6-28 |
| 3 | Authors | Lammers M. Rose R. Scrima A. Wittinghofer A. |
| Title | The regulation of mDia1 by autoinhibition and its release by Rho*GTP. | |
| Source | EMBO J. 24:4176-4187(2005). | |
| PubMed ID | 16292343 | |
| DOI | 10.1038/sj.emboj.7600879 |
| 4 | Authors | Nezami A.G. Poy F. Eck M.J. |
| Title | Structure of the autoinhibitory switch in formin mDia1. | |
| Source | Structure 14:257-263(2006). | |
| PubMed ID | 16472745 | |
| DOI | 10.1016/j.str.2005.12.003 |
| 5 | Authors | Alberts A.S. |
| Title | Identification of a carboxyl-terminal diaphanous-related formin homology protein autoregulatory domain. | |
| Source | J. Biol. Chem. 276:2824-2830(2001). | |
| PubMed ID | 11035012 | |
| DOI | 10.1074/jbc.M006205200 |
| 6 | Authors | Wallar B.J. Stropich B.N. Schoenherr J.A. Holman H.A. Kitchen S.M. Alberts A.S. |
| Title | The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the diaphanous-related formin inhibitory domain. | |
| Source | J. Biol. Chem. 281:4300-4307(2006). | |
| PubMed ID | 16361707 | |
| DOI | 10.1074/jbc.M510277200 |
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