SOS1

SOS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSOS1, GF1, GGF1, GINGF, HGF, NS4, SOS Ras/Rac guanine nucleotide exchange factor 1, SOS-1
External IDsOMIM: 182530; MGI: 98354; HomoloGene: 4117; GeneCards: SOS1; OMA:SOS1 - orthologs
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 MbChr 17: 80.7 – 80.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

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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

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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

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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

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SOS1 has been shown to interact with:

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115904 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024241 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. ^ Xiao S, Wang X, Qu B, Yang M, Liu G, Bu L, et al. (September 2000). "Refinement of the locus for autosomal dominant hereditary gingival fibromatosis (GINGF) to a 3.8-cM region on 2p21". Genomics. 68 (3): 247–252. doi:10.1006/geno.2000.6285. PMID 10995566.
  7. ^ "Entrez Gene: SOS1 son of sevenless homolog 1 (Drosophila)".
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  9. ^ Hart TC, Zhang Y, Gorry MC, Hart PS, Cooper M, Marazita ML, et al. (April 2002). "A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1". American Journal of Human Genetics. 70 (4): 943–954. doi:10.1086/339689. PMC 379122. PMID 11868160.
  10. ^ Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, et al. (December 2001). "Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome". Nature Genetics. 29 (4): 465–468. doi:10.1038/ng772. PMID 11704759. S2CID 14627986.
  11. ^ Hillig RC, Sautier B, Schroeder J, Moosmayer D, Hilpmann A, Stegmann CM, et al. (February 2019). "Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction". Proceedings of the National Academy of Sciences of the United States of America. 116 (7): 2551–2560. Bibcode:2019PNAS..116.2551H. doi:10.1073/pnas.1812963116. PMC 6377443. PMID 30683722.
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Further reading

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

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