Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0SHIZ6)

• DOT Name: Protein sprouty homolog 3 (SPRY3)
• Synonyms: Spry-3; Sprouty RTK signaling antagonist 3; Sprouty3
• Gene Name: SPRY3
• Related Disease:
  Autism
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: SPY3_HUMAN
• Pfam ID: PF05210
• Sequence:
  MDAAVTDDFQQILPIEQLRSTHASNDYVERPPAPCKQALSSPSLIVQTHKSDWSLATMPT
  SLPRSLSQCHQLQPLPQHLSQSSIASSMSHSTTASDQRLLASITPSPSGQSIIRTQPGAG
  VHPKADGALKGEAEQSAGHPSEHLFICEECGRCKCVPCTAARPLPSCWLCNQRCLCSAES
  LLDYGTCLCCVKGLFYHCSTDDEDNCADEPCSCGPSSCFVRWAAMSLISLFLPCLCCYLP
  TRGCLHLCQQGYDSLRRPGCRCKRHTNTVCRKISSGSAPFPKAQEKSV
• Function: Inhibits neurite branching, arbor length and neurite complexity. Inhibits EGF-mediated p42/44 ERK signaling. Negatively regulates the MAPK cascade, resulting in a reduction of extracellular matrix protein accumulation. May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.
• Tissue Specificity: Widely expressed; particularly in the fetal tissues. Expressed in the brain with expression the highest in Purkinje cells in the cerebellum (at protein level) . Expressed in the myocardium of the heart .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Genetic Variation	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein sprouty homolog 3 (SPRY3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein sprouty homolog 3 (SPRY3).	[5]

References

• [1] Regulation of SPRY3 by X chromosome and PAR2-linked promoters in an autism susceptibility region.Hum Mol Genet. 2015 Sep 15;24(18):5126-41. doi: 10.1093/hmg/ddv231. Epub 2015 Jun 18.
• [2] Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells.Cells. 2019 Aug 1;8(8):808. doi: 10.3390/cells8080808.
• [3] Differential expression of sprouty genes in hepatocellular carcinoma.J Surg Oncol. 2012 Mar;105(3):273-6. doi: 10.1002/jso.22095. Epub 2011 Sep 19.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.