Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2VI301)

• DOT Name: Small vasohibin-binding protein (SVBP)
• Synonyms: Coiled coil domain-containing protein 23
• Gene Name: SVBP
• Related Disease:
  Hepatocellular carcinoma
  Intellectual disability
  Syndromic intellectual disability
• UniProt ID: SVBP_HUMAN
• PDB ID: 6J4O; 6J4P; 6J4Q; 6J4S; 6J4U; 6J4V; 6J7B; 6J8F; 6J8N; 6J8O; 6J91; 6J9H; 6JZC; 6JZD; 6JZE; 6K81; 6LPG; 6NVQ; 6OCF; 6OCG; 6OCH; 6QBY; 6WSL; 7ZCW
• Pfam ID: PF15674
• Sequence:
  MDPPARKEKTKVKESVSRVEKAKQKSAQQELKQRQRAEIYALNRVMTELEQQQFDEFCKQ
  MQPPGE
• Function: Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin. This activity is critical for spindle function and accurate chromosome segregation during mitosis since microtubule detyronisation regulates mitotic spindle length and postioning. Also required to enhance the solubility and secretion of VASH1 and VASH2. Plays a role in axon and excitatory synapse formation.
• Reactome Pathway: Carboxyterminal post-translational modifications of tubulin (R-HSA-8955332)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[2]
Syndromic intellectual disability	DISH7SDF	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Small vasohibin-binding protein (SVBP).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small vasohibin-binding protein (SVBP).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Small vasohibin-binding protein (SVBP).	[6]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Small vasohibin-binding protein (SVBP).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Small vasohibin-binding protein (SVBP).	[5]

References

• [1] Vasohibin 2 is transcriptionally activated and promotes angiogenesis in hepatocellular carcinoma.Oncogene. 2013 Mar 28;32(13):1724-34. doi: 10.1038/onc.2012.177. Epub 2012 May 21.
• [2] Loss of function of SVBP leads to autosomal recessive intellectual disability, microcephaly, ataxia, and hypotonia. Genet Med. 2019 Aug;21(8):1790-1796. doi: 10.1038/s41436-018-0415-8. Epub 2019 Jan 4.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.