Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ9WPKY)

• DOT Name: Small proline-rich protein 2B (SPRR2B)
• Synonyms: SPR-2B
• Gene Name: SPRR2B
• Related Disease:
  Asthma
  Cardiac disease
  Cardiac failure
  Congestive heart failure
• UniProt ID: SPR2B_HUMAN
• Pfam ID: PF14820
• Sequence:
  MSYQQQQCKQPCQPPPVCPTPKCPEPCPPPKCPEPCPPPKCPQPCPPQQCQQKYPPVTPS
  PPCQPKYPPKSK
• Function: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.
• Tissue Specificity: Suprabasal layers of squamous-differentiated tissues such as epidermis, esophagus, tongue and trachea.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Strong	Genetic Variation	[1]
Cardiac disease	DISVO1I5	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small proline-rich protein 2B (SPRR2B).	[3]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Small proline-rich protein 2B (SPRR2B).	[4]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Small proline-rich protein 2B (SPRR2B).	[3]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Small proline-rich protein 2B (SPRR2B).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small proline-rich protein 2B (SPRR2B).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small proline-rich protein 2B (SPRR2B).	[8]

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 Small proline-rich protein 2B (SPRR2B).	[6]

References

• [1] Genetic variation in small proline rich protein 2B as a predictor for asthma among children with eczema.Ann Allergy Asthma Immunol. 2012 Mar;108(3):145-50. doi: 10.1016/j.anai.2012.01.004.
• [2] Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure.Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3436-E3445. doi: 10.1073/pnas.1717423115. Epub 2018 Mar 26.
• [3] Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: implication in skin irritation. J Dermatol Sci. 2014 Nov;76(2):112-9. doi: 10.1016/j.jdermsci.2014.08.003. Epub 2014 Aug 26.
• [4] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [5] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [6] 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.
• [7] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.