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SOS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases SOS1, GF1, GGF1, GINGF, HGF, NS4, SOS Ras/Rac guanine nucleotide exchange factor 1, SOS-1
External IDs OMIM: 182530 MGI: 98354 HomoloGene: 4117 GeneCards: SOS1
Orthologs
SpeciesHumanMouse
Entrez

6654

20662

Ensembl

ENSG00000115904

ENSMUSG00000024241

UniProt

Q07889

Q62245

RefSeq (mRNA)

NM_005633
NM_001382394
NM_001382395

NM_009231

RefSeq (protein)

NP_005624
NP_001369323
NP_001369324

NP_033257

Location (UCSC) Chr 2: 38.96 – 39.12 Mb Chr 17: 80.7 – 80.79 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene. [5] [6]

Function

SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with Ras proteins to phosphorylate GDP into GTP, or from an inactive state to an active state to signal cell proliferation. RAS genes (e.g., MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). The first exchange factor to be identified for RAS was the S. cerevisiae Cdc25 gene product (not to be confused with the S. pombe Cdc25). Genetic analysis indicated that CDC25 is essential for activation of RAS proteins. In Drosophila, the protein encoded by the 'son of sevenless' gene (Sos) contains a domain that shows sequence similarity with the catalytic domain of Cdc25. Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange. [7]

Clinical significance

Recent studies also show that mutations in Sos1 can cause Noonan syndrome [8] and hereditary gingival fibromatosis type 1. [9] Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes. [10] activators of the MAP kinase pathway.

Inhibitors and activators

In 2019, the first SOS1 inhibitor, BAY-293, [11] was published which met the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium. [12] Shortly after, the discovery of BI-3406 [13] [14] was published.

In 2018, Fesik et al. reported the discovery of benzimidazole-derived SOS1 activators [15] (e.g. VUBI1).

Interactions

SOS1 has been shown to interact with:

See also

References

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  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024241 – Ensembl, May 2017
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Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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