Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTNP6H7)

DOT Name	Fibroblast growth factor receptor substrate 3 (FRS3)
Synonyms	FGFR substrate 3; FGFR-signaling adaptor SNT2; Suc1-associated neurotrophic factor target 2; SNT-2
Gene Name	FRS3
Related Disease	Neoplasm ( ) Non-small-cell lung cancer ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	FRS3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2KUP; 2KUQ; 2YS5; 2YT2
Pfam ID	PF02174
Sequence	MGSCCSCLNRDSVPDNHPTKFKVTNVDDEGVELGSGVMELTQSELVLHLHRREAVRWPYL CLRRYGYDSNLFSFESGRRCQTGQGIFAFKCSRAEEIFNLLQDLMQCNSINVMEEPVIIT RNSHPAELDLPRAPQPPNALGYTVSSFSNGCPGEGPRFSAPRRLSTSSLRHPSLGEESTH ALIAPDEQSHTYVNTPASEDDHRRGRHCLQPLPEGQAPFLPQARGPDQRDPQVFLQPGQV KFVLGPTPARRHMVKCQGLCPSLHDPPHHNNNNEAPSECPAQPKCTYENVTGGLWRGAGW RLSPEEPGWNGLAHRRAALLHYENLPPLPPVWESQAQQLGGEAGDDGDSRDGLTPSSNGF PDGEEDETPLQKPTSTRAAIRSHGSFPVPLTRRRGSPRVFNFDFRRPGPEPPRQLNYIQV ELKGWGGDRPKGPQNPSSPQAPMPTTHPARSSDSYAVIDLKKTVAMSNLQRALPRDDGTA RKTRHNSTDLPL
Function	Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2.
Reactome Pathway	FRS-mediated FGFR2 signaling (R-HSA-5654700 ) FRS-mediated FGFR3 signaling (R-HSA-5654706 ) FRS-mediated FGFR4 signaling (R-HSA-5654712 ) RAF/MAP kinase cascade (R-HSA-5673001 ) Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731 ) RND2 GTPase cycle (R-HSA-9696270 ) RND1 GTPase cycle (R-HSA-9696273 ) Signaling by ALK fusions and activated point mutants (R-HSA-9725370 ) FRS-mediated FGFR1 signaling (R-HSA-5654693 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	moderate	Biomarker	[3]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Fibroblast growth factor receptor substrate 3 (FRS3).	[4]
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References

1	Adaptor protein complex of FRS2 and CIN85/CD2AP provides a novel mechanism for ErbB2/HER2 protein downregulation.Cancer Sci. 2013 Mar;104(3):345-52. doi: 10.1111/cas.12086. Epub 2013 Feb 8.
2	FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding.Oncogene. 2010 May 27;29(21):3087-99. doi: 10.1038/onc.2010.69. Epub 2010 Mar 15.
3	Role and expression of FRS2 and FRS3 in prostate cancer.BMC Cancer. 2011 Nov 11;11:484. doi: 10.1186/1471-2407-11-484.
4	Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.