Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTITDZW9)

• DOT Name: Serine palmitoyltransferase small subunit B (SPTSSB)
• Synonyms: Protein ADMP; Small subunit of serine palmitoyltransferase B; ssSPTb
• Gene Name: SPTSSB
• Related Disease: Parkinson disease
• UniProt ID: SPTSB_HUMAN
• Pfam ID: PF11779
• Sequence:
  MDLRRVKEYFSWLYYQYQIISCCAVLEPWERSMFNTILLTIIAMVVYTAYVFIPIHIRLA
  WEFFSKICGYHSTISN
• Function: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. Within the SPT complex, SPTSSB stimulates the catalytic activity and plays a role in substrate specificity. SPT complexes with this subunit showing a preference for longer acyl-CoAs. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.
• Tissue Specificity: Expression is seen predominantly in the prostate epithelium with weaker expression in the fibroblasts and endothelial cells.
• KEGG Pathway: Sphingolipid sig.ling pathway (hsa04071)
• Reactome Pathway: Sphingolipid de novo biosynthesis (R-HSA-1660661)
• BioCyc Pathway: MetaCyc:MONOMER66-34372

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Serine palmitoyltransferase small subunit B (SPTSSB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine palmitoyltransferase small subunit B (SPTSSB).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine palmitoyltransferase small subunit B (SPTSSB).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serine palmitoyltransferase small subunit B (SPTSSB).	[5]

References

• [1] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] 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.