Structural highlights
Function
[TIAM1_MOUSE] Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA (By similarity). Affects invasiveness of T-lymphoma cells.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Tiam1 and Tiam2 (Tiam1/2) are guanine nucleotide-exchange factors that possess the PH-CC-Ex (pleckstrin homology, coiled coil and extra) region that mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. Crystal structures of the PH-CC-Ex regions revealed a single globular domain, PHCCEx domain, comprising a conventional PH subdomain associated with an antiparallel coiled coil of CC subdomain and a novel three-helical globular Ex subdomain. The PH subdomain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. Mutational and binding studies indicated that CC and Ex subdomains form a positively charged surface for protein binding. We identified two unique acidic sequence motifs in Tiam1/2-interacting proteins for binding to PHCCEx domain, Motif-I in CD44 and ephrinB's and the NMDA receptor, and Motif-II in Par3 and JIP2. Our results suggest the molecular basis by which the Tiam1/2 PHCCEx domain facilitates dual binding to membranes and signalling proteins.
The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module.,Terawaki S, Kitano K, Mori T, Zhai Y, Higuchi Y, Itoh N, Watanabe T, Kaibuchi K, Hakoshima T EMBO J. 2010 Jan 6;29(1):236-50. Epub 2009 Nov 5. PMID:19893486[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Terawaki S, Kitano K, Mori T, Zhai Y, Higuchi Y, Itoh N, Watanabe T, Kaibuchi K, Hakoshima T. The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module. EMBO J. 2010 Jan 6;29(1):236-50. Epub 2009 Nov 5. PMID:19893486 doi:10.1038/emboj.2009.323
