D
IPR000651

Ras-like guanine nucleotide exchange factor, N-terminal

InterPro entry
Short nameRas-like_Gua-exchang_fac_N
Overlapping
homologous
superfamilies
 

Description

The N-terminal domain of guanine nucleotide exchange factor (GEF) for Ras-like GTPases is also called REM domain (Ras exchanger motif). REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few
[8, 2, 3, 4, 5, 6, 7, 1]
.

The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved
[1]
. The structure consists of two distinct α helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. The N-terminal domain is likely to be important for the stability and correct placement of the hairpin structure.

This entry represents a domain found in several GEF for Ras-like small GTPases which lies N-terminal to the RasGef (Cdc25-like) domain.

References

1.The structural basis of the activation of Ras by Sos. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J. Nature 394, 337-43, (1998). View articlePMID: 9690470

2.GEFs in growth factor signaling. Bernards A, Settleman J. Growth Factors 25, 355-61, (2007). View articlePMID: 18236214

3.Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. Quilliam LA, Khosravi-Far R, Huff SY, Der CJ. Bioessays 17, 395-404, (1995). View articlePMID: 7786285

4.Proteins regulating Ras and its relatives. Boguski MS, McCormick F. Nature 366, 643-54, (1993). View articlePMID: 8259209

5.Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J. Nature 363, 85-8, (1993). View articlePMID: 8479541

6.Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state. Rehmann H, Das J, Knipscheer P, Wittinghofer A, Bos JL. Nature 439, 625-8, (2006). View articlePMID: 16452984

7.Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS. Margarit SM, Sondermann H, Hall BE, Nagar B, Hoelz A, Pirruccello M, Bar-Sagi D, Kuriyan J. Cell 112, 685-95, (2003). View articlePMID: 12628188

8.Many faces of Ras activation. Buday L, Downward J. Biochim. Biophys. Acta 1786, 178-87, (2008). View articlePMID: 18541156

Cross References

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