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Fibroblast growth factor receptor substrate 2
Protein FRS2 PDB 1xr0.png
PDB rendering based on 1xr0.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols FRS2 ; FRS2A; FRS2alpha; SNT; SNT-1; SNT1
External IDs OMIM607743 MGI1100860 HomoloGene4846 GeneCards: FRS2 Gene
RNA expression pattern
PBB GE FRS2 221308 at tn.png
More reference expression data
Species Human Mouse
Entrez 10818 327826
Ensembl ENSG00000166225 ENSMUSG00000020170
UniProt Q8WU20 Q8C180
RefSeq (mRNA) NM_001042555 NM_177798
RefSeq (protein) NP_001036020 NP_808466
Location (UCSC) Chr 12:
69.86 – 69.97 Mb
Chr 10:
117.07 – 117.15 Mb
PubMed search [1] [2]

Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the FRS2 gene.[1][2][3]

FRS2 is overexpressed and amplified in several cancer types, including prostate cancer.[4][5]


FRS2 has been shown to interact with PRKCI,[6] Grb2,[7][8][9][10] PTPN11,[11][12][13] Fibroblast growth factor receptor 1,[2][14][15][16] TrkA,[9] Cbl gene[8] and SOS1.[8][10][17]


  1. ^ Wang JK, Xu H, Li HC, Goldfarb M (October 1996). "Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras". Oncogene 13 (4): 721–9. PMID 8761293. 
  2. ^ a b Xu H, Lee KW, Goldfarb M (August 1998). "Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins". J Biol Chem 273 (29): 17987–90. doi:10.1074/jbc.273.29.17987. PMID 9660748. 
  3. ^ "Entrez Gene: FRS2 Fibroblast growth factor receptor substrate 2". 
  4. ^ Valencia, T; Joseph, A; Kachroo, N; Darby, S; Meakin, S; Gnanapragasam, VJ (Nov 11, 2011). "Role and expression of FRS2 and FRS3 in prostate cancer.". BMC cancer 11: 484. PMID 22078327. 
  5. ^ Chen, Y; McGee, J; Chen, X; Doman, TN; Gong, X; Zhang, Y; Hamm, N; Ma, X; Higgs, RE; Bhagwat, SV; Buchanan, S; Peng, SB; Staschke, KA; Yadav, V; Yue, Y; Hosein, Kouros-Mehr (2014). "Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets.". PloS one 9 (5): e98293. PMID 24874471. 
  6. ^ Lim, Y P; Low B C; Lim J; Wong E S; Guy G R (July 1999). "Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling". J. Biol. Chem. (UNITED STATES) 274 (27): 19025–34. doi:10.1074/jbc.274.27.19025. ISSN 0021-9258. PMID 10383403. 
  7. ^ Ong, S H; Goh K C; Lim Y P; Low B C; Klint P; Claesson-Welsh L; Cao X; Tan Y H; Guy G R (August 1996). "Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2". Biochem. Biophys. Res. Commun. (UNITED STATES) 225 (3): 1021–6. doi:10.1006/bbrc.1996.1288. ISSN 0006-291X. PMID 8780727. 
  8. ^ a b c Wong, Andy; Lamothe Betty; Lee Arnold; Schlessinger Joseph; Lax Irit; Li Arnold (May 2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (10): 6684–9. doi:10.1073/pnas.052138899. ISSN 0027-8424. PMC 124463. PMID 11997436. 
  9. ^ a b Meakin, S O; MacDonald J I; Gryz E A; Kubu C J; Verdi J M (April 1999). "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem. (UNITED STATES) 274 (14): 9861–70. doi:10.1074/jbc.274.14.9861. ISSN 0021-9258. PMID 10092678. 
  10. ^ a b Kouhara, H; Hadari Y R; Spivak-Kroizman T; Schilling J; Bar-Sagi D; Lax I; Schlessinger J (May 1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell (UNITED STATES) 89 (5): 693–702. doi:10.1016/S0092-8674(00)80252-4. ISSN 0092-8674. PMID 9182757. 
  11. ^ Delahaye, L; Rocchi S; Van Obberghen E (February 2000). "Potential involvement of FRS2 in insulin signaling". Endocrinology (UNITED STATES) 141 (2): 621–8. doi:10.1210/en.141.2.621. ISSN 0013-7227. PMID 10650943. 
  12. ^ Kurokawa, K; Iwashita T; Murakami H; Hayashi H; Kawai K; Takahashi M (April 2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene (England) 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. ISSN 0950-9232. PMID 11360177. 
  13. ^ Hadari, Y R; Kouhara H; Lax I; Schlessinger J (July 1998). "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Mol. Cell. Biol. (UNITED STATES) 18 (7): 3966–73. ISSN 0270-7306. PMC 108981. PMID 9632781. 
  14. ^ Yan, Kelley S; Kuti Miklos, Yan Sherry, Mujtaba Shiraz, Farooq Amjad, Goldfarb Mitchell P, Zhou Ming-Ming (May 2002). "FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors". J. Biol. Chem. (United States) 277 (19): 17088–94. doi:10.1074/jbc.M107963200. ISSN 0021-9258. PMID 11877385. 
  15. ^ Ong, S H; Guy G R; Hadari Y R; Laks S; Gotoh N; Schlessinger J; Lax I (February 2000). "FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors". Mol. Cell. Biol. (UNITED STATES) 20 (3): 979–89. doi:10.1128/MCB.20.3.979-989.2000. ISSN 0270-7306. PMC 85215. PMID 10629055. 
  16. ^ Dhalluin, C; Yan K S; Plotnikova O; Lee K W; Zeng L; Kuti M; Mujtaba S; Goldfarb M P; Zhou M M (October 2000). "Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors". Mol. Cell (United States) 6 (4): 921–9. doi:10.1016/S1097-2765(05)00087-0. ISSN 1097-2765. PMID 11090629. 
  17. ^ Foehr, E D; Tatavos A; Tanabe E; Raffioni S; Goetz S; Dimarco E; De Luca M; Bradshaw R A (May 2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB J. (UNITED STATES) 14 (7): 973–81. ISSN 0892-6638. PMID 10783152. 

Further reading[edit]