Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWCJTT3)

• DOT Name: Sushi domain-containing protein 4 (SUSD4)
• Gene Name: SUSD4
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: SUSD4_HUMAN
• Pfam ID: PF00084
• Sequence:
  MYHGMNPSNGDGFLEQQQQQQQPQSPQRLLAVILWFQLALCFGPAQLTGGFDDLQVCADP
  GIPENGFRTPSGGVFFEGSVARFHCQDGFKLKGATKRLCLKHFNGTLGWIPSDNSICVQE
  DCRIPQIEDAEIHNKTYRHGEKLIITCHEGFKIRYPDLHNMVSLCRDDGTWNNLPICQGC
  LRPLASSNGYVNISELQTSFPVGTVISYRCFPGFKLDGSAYLECLQNLIWSSSPPRCLAL
  EVCPLPPMVSHGDFVCHPRPCERYNHGTVVEFYCDPGYSLTSDYKYITCQYGEWFPSYQV
  YCIKSEQTWPSTHETLLTTWKIVAFTATSVLLVLLLVILARMFQTKFKAHFPPRGPPRSS
  SSDPDFVVVDGVPVMLPSYDEAVSGGLSALGPGYMASVGQGCPLPVDDQSPPAYPGSGDT
  DTGPGESETCDSVSGSSELLQSLYSPPRCQESTHPASDNPDIIASTAEEVASTSPGIDIA
  DEIPLMEEDP
• Function: Acts as a complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.
• Tissue Specificity: Isoform 3 is the predominant isoform in all tissues except cortex, cerebellum, kidney, and breast. Isoform 1 is found primarily in the esophagus and the brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]

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 Sushi domain-containing protein 4 (SUSD4).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sushi domain-containing protein 4 (SUSD4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sushi domain-containing protein 4 (SUSD4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sushi domain-containing protein 4 (SUSD4).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Sushi domain-containing protein 4 (SUSD4).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sushi domain-containing protein 4 (SUSD4).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sushi domain-containing protein 4 (SUSD4).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sushi domain-containing protein 4 (SUSD4).	[9]

References

• [1] The human complement inhibitor Sushi Domain-Containing Protein 4 (SUSD4) expression in tumor cells and infiltrating T cells is associated with better prognosis of breast cancer patients.BMC Cancer. 2015 Oct 19;15:737. doi: 10.1186/s12885-015-1734-7.
• [2] 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.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message. Toxicol Sci. 2010 Aug;116(2):549-61.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.