Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRKRW50)

• DOT Name: Cystatin-SA (CST2)
• Synonyms: Cystatin-2; Cystatin-S5
• Gene Name: CST2
• Related Disease:
  Bacterial vaginosis
  Diabetic kidney disease
  Head-neck squamous cell carcinoma
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Oral lichen planus
  Ovarian cancer
  Periodontal disease
  Asthma
• UniProt ID: CYTT_HUMAN
• Pfam ID: PF00031
• Sequence:
  MAWPLCTLLLLLATQAVALAWSPQEEDRIIEGGIYDADLNDERVQRALHFVISEYNKATE
  DEYYRRLLRVLRAREQIVGGVNYFFDIEVGRTICTKSQPNLDTCAFHEQPELQKKQLCSF
  QIYEVPWEDRMSLVNSRCQEA
• Function: Thiol protease inhibitor.
• Tissue Specificity: Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in submandibular gland and parotid gland.
• KEGG Pathway: Salivary secretion (hsa04970)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacterial vaginosis	DISK2MZ2	Strong	Biomarker	[1]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[2]
Oral lichen planus	DISVEAJA	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Periodontal disease	DISJQHVN	Strong	Biomarker	[2]
Asthma	DISW9QNS	Disputed	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cystatin-SA (CST2).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cystatin-SA (CST2).	[9]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Cystatin-SA (CST2).	[10]

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 Cystatin-SA (CST2).	[11]

References

• [1] Factors associated with the composition and diversity of the cervical microbiota of reproductive-age Black South African women: a retrospective cross-sectional study.PeerJ. 2019 Aug 15;7:e7488. doi: 10.7717/peerj.7488. eCollection 2019.
• [2] Salivary and serum cystatin SA levels in patients with type 2 diabetes mellitus or diabetic nephropathy.Arch Oral Biol. 2019 Aug;104:67-75. doi: 10.1016/j.archoralbio.2019.05.020. Epub 2019 May 22.
• [3] Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis.Br J Cancer. 2004 May 17;90(10):1961-8. doi: 10.1038/sj.bjc.6601830.
• [4] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [5] Expression of high molecular weight cysteine proteinase inhibitor in ovarian cancer tissues: regulation of cathepsin B expression by placental CPI.Biol Chem. 2003 Jul;384(7):1103-7. doi: 10.1515/BC.2003.123.
• [6] Putative salivary protein biomarkers for the diagnosis of oral lichen planus: a case-control study.BMC Oral Health. 2018 Mar 13;18(1):42. doi: 10.1186/s12903-018-0504-8.
• [7] Discriminant analysis followed by unsupervised cluster analysis including exosomal cystatins predict presence of chronic rhinosinusitis, phenotype, and disease severity.Int Forum Allergy Rhinol. 2019 Sep;9(9):1069-1076. doi: 10.1002/alr.22380. Epub 2019 Jul 19.
• [8] 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.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [11] 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.