Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0XGQ93)

• DOT Name: SAM and SH3 domain-containing protein 3 (SASH3)
• Synonyms: SH3 protein expressed in lymphocytes homolog
• Gene Name: SASH3
• Related Disease:
  Combined immunodeficiency, X-linked
  Immunodeficiency 102
  Neoplasm
• UniProt ID: SASH3_HUMAN
• Pfam ID: PF00536 ; PF07653 ; PF12485
• Sequence:
  MLRRKPSNASEKEPTQKKKLSLQRSSSFKDFAKSKPSSPVVSEKEFNLDDNIPEDDSGVP
  TPEDAGKSGKKLGKKWRAVISRTMNRKMGKMMVKALSEEMADTLEEGSASPTSPDYSLDS
  PGPEKMALAFSEQEEHELPVLSRQASTGSELCSPSPGSGSFGEEPPAPQYTGPFCGRARV
  HTDFTPSPYDHDSLKLQKGDVIQIIEKPPVGTWLGLLNGKVGSFKFIYVDVLPEEAVGHA
  RPSRRQSKGKRPKPKTLHELLERIGLEEHTSTLLLNGYQTLEDFKELRETHLNELNIMDP
  QHRAKLLTAAELLLDYDTGSEEAEEGAESSQEPVAHTVSEPKVDIPRDSGCFEGSESGRD
  DAELAGTEEQLQGLSLAGAP
• Function: May function as a signaling adapter protein in lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined immunodeficiency, X-linked	DISQX1XE	Strong	X-linked	[1]
Immunodeficiency 102	DISOYO9P	Strong	X-linked	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SAM and SH3 domain-containing protein 3 (SASH3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of SAM and SH3 domain-containing protein 3 (SASH3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SAM and SH3 domain-containing protein 3 (SASH3).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SAM and SH3 domain-containing protein 3 (SASH3).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of SAM and SH3 domain-containing protein 3 (SASH3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SAM and SH3 domain-containing protein 3 (SASH3).	[9]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development. BMC Immunol. 2009 Jul 15;10:38. doi: 10.1186/1471-2172-10-38.
• [3] Overexpression of SASH1 Inhibits TGF-1-Induced EMT in Gastric Cancer Cells.Oncol Res. 2016;24(1):17-23. doi: 10.3727/096504016X14570992647203.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.