Function

Son of sevenless or Ras-specific nucleotide exchange factor SOS or son of sevenless homolog or son of sevenless protein homolog (SOS) is a Ras activator in signalling pathways. In mammals SOS is involved in coupling signals originated by cell surface receptor tyrosine kinases to Ras-dependent mitogenic signalling pathways[1]. SOS is a multi-domain protein whose catalytic domain (homologous to Cdc25 see Dual specificity phosphatase) is active towards Ras and its Dbl holology and pleckstrin homology domains are active in stimulating GTP/GDP exchage.

Disease

Mutations in SOS1 have been reported in Noonan syndrome and in type 1 hereditary gingival fibromatosis[2].

Structural highlights

SOS1 domain structure contains histone domain (HD) residues 1-191, Dbl homology domain (DH) 203-389, pleckstrin homology domain (PH) 443-548, Ras exchange motif (REM) 601-648, catalytic domain 782-1020 and proline-rich region (PR) 1146-1297.

3D structures of son of sevenless

Son of sevenless 3D structures

References

  1. Rojas JM, Oliva JL, Santos E. Mammalian son of sevenless Guanine nucleotide exchange factors: old concepts and new perspectives. Genes Cancer. 2011 Mar;2(3):298-305. doi: 10.1177/1947601911408078. PMID:21779500 doi:http://dx.doi.org/10.1177/1947601911408078
  2. Pierre S, Bats AS, Coumoul X. Understanding SOS (Son of Sevenless). Biochem Pharmacol. 2011 Nov 1;82(9):1049-56. doi: 10.1016/j.bcp.2011.07.072. Epub, 2011 Jul 20. PMID:21787760 doi:http://dx.doi.org/10.1016/j.bcp.2011.07.072

Human SOS1 REM+catalytic domains (olive) complex with HRas (green, blue), GTP, phosphate and Mg++ ion (green) (PDB code 1nvx)

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Michal Harel, Alexander Berchansky