Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ZVT8R)

• DOT Name: SPRY domain-containing SOCS box protein 2 (SPSB2)
• Synonyms: SSB-2; Gene-rich cluster protein C9
• Gene Name: SPSB2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Hepatitis C virus infection
• UniProt ID: SPSB2_HUMAN
• PDB ID: 3EMW; 5XN3; 6DN5; 6DN6; 6JKJ; 6JWM; 6JWN; 6KEY
• Pfam ID: PF07525 ; PF00622
• Sequence:
  MGQTALAGGSSSTPTPQALYPDLSCPEGLEELLSAPPPDLGAQRRHGWNPKDCSENIEVK
  EGGLYFERRPVAQSTDGARGKRGYSRGLHAWEISWPLEQRGTHAVVGVATALAPLQTDHY
  AALLGSNSESWGWDIGRGKLYHQSKGPGAPQYPAGTQGEQLEVPERLLVVLDMEEGTLGY
  AIGGTYLGPAFRGLKGRTLYPAVSAVWGQCQVRIRYLGERRAEPHSLLHLSRLCVRHNLG
  DTRLGQVSALPLPPAMKRYLLYQ
• Function: Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2. Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[2]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[3]

8 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 SPRY domain-containing SOCS box protein 2 (SPSB2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SPRY domain-containing SOCS box protein 2 (SPSB2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SPRY domain-containing SOCS box protein 2 (SPSB2).	[10]

References

• [1] Antitumor effects of saikosaponin b2 on breast cancer cell proliferation and migration.Mol Med Rep. 2019 Aug;20(2):1943-1951. doi: 10.3892/mmr.2019.10385. Epub 2019 Jun 13.
• [2] Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.Gastroenterology. 2016 Jun;150(7):1633-1645. doi: 10.1053/j.gastro.2016.02.076. Epub 2016 Mar 8.
• [3] SPSB2 inhibits hepatitis C virus replication by targeting NS5A for ubiquitination and degradation.PLoS One. 2019 Jul 25;14(7):e0219989. doi: 10.1371/journal.pone.0219989. eCollection 2019.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.