Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1E6IP)

• DOT Name: Serpin A12 (SERPINA12)
• Synonyms: OL-64; Visceral adipose tissue-derived serine protease inhibitor; Vaspin; Visceral adipose-specific serpin
• Gene Name: SERPINA12
• Related Disease:
  Adult respiratory distress syndrome
  Arteriosclerosis
  Atherosclerosis
  Dilated cardiomyopathy 1A
  Obstructive sleep apnea
  Polycystic ovarian syndrome
  Pulmonary arterial hypertension
  Type-1/2 diabetes
  Hereditary palmoplantar keratoderma, Gamborg-Nielsen type
  Coronary atherosclerosis
  Obesity
• UniProt ID: SPA12_HUMAN
• PDB ID: 4IF8; 4Y3K; 4Y40; 5EI0
• Pfam ID: PF00079
• Sequence:
  MNPTLGLAIFLAVLLTVKGLLKPSFSPRNYKALSEVQGWKQRMAAKELARQNMDLGFKLL
  KKLAFYNPGRNIFLSPLSISTAFSMLCLGAQDSTLDEIKQGFNFRKMPEKDLHEGFHYII
  HELTQKTQDLKLSIGNTLFIDQRLQPQRKFLEDAKNFYSAETILTNFQNLEMAQKQINDF
  ISQKTHGKINNLIENIDPGTVMLLANYIFFRARWKHEFDPNVTKEEDFFLEKNSSVKVPM
  MFRSGIYQVGYDDKLSCTILEIPYQKNITAIFILPDEGKLKHLEKGLQVDTFSRWKTLLS
  RRVVDVSVPRLHMTGTFDLKKTLSYIGVSKIFEEHGDLTKIAPHRSLKVGEAVHKAELKM
  DERGTEGAAGTGAQTLPMETPLVVKIDKPYLLLIYSEKIPSVLFLGKIVNPIGK
• Function: Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.
• Tissue Specificity: Expressed in visceral adipose tissues.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[3]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[4]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[5]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Biomarker	[6]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[3]
Hereditary palmoplantar keratoderma, Gamborg-Nielsen type	DIS8E1MP	Supportive	Autosomal recessive	[7]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[8]
Obesity	DIS47Y1K	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Serpin A12 (SERPINA12).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Serpin A12 (SERPINA12).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serpin A12 (SERPINA12).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Serpin A12 (SERPINA12).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serpin A12 (SERPINA12).	[14]

References

• [1] Vaspin protects against LPSinduced ARDS by inhibiting inflammation, apoptosis and reactive oxygen species generation in pulmonary endothelial cells via the Akt/GSK? pathway.Int J Mol Med. 2017 Dec;40(6):1803-1817. doi: 10.3892/ijmm.2017.3176. Epub 2017 Oct 9.
• [2] Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-B/miR-33a pathway in THP-1 macropahge-derived foam cells.Biochem Biophys Res Commun. 2018 Jun 2;500(2):318-324. doi: 10.1016/j.bbrc.2018.04.066. Epub 2018 Apr 17.
• [3] Vaspin prevents myocardial injury in rats model of diabetic cardiomyopathy by enhancing autophagy and inhibiting inflammation.Biochem Biophys Res Commun. 2019 Jun 18;514(1):1-8. doi: 10.1016/j.bbrc.2019.04.110. Epub 2019 Apr 20.
• [4] Changes in four plasma adipokines before and after sleep in OSAS patients.Clin Respir J. 2017 Nov;11(6):968-974. doi: 10.1111/crj.12449. Epub 2016 Mar 10.
• [5] Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance.Diabetes. 2008 Jun;57(6):1501-7. doi: 10.2337/db08-0127. Epub 2008 Mar 28.
• [6] Visceral adipose tissue-derived serine protease inhibitor prevents the development of monocrotaline-induced pulmonary arterial hypertension in rats.Pflugers Arch. 2017 Nov;469(11):1425-1432. doi: 10.1007/s00424-017-2043-6. Epub 2017 Aug 3.
• [7] Loss-of-Function Variants in SERPINA12 Underlie Autosomal Recessive Palmoplantar Keratoderma. J Invest Dermatol. 2020 Nov;140(11):2178-2187. doi: 10.1016/j.jid.2020.02.030. Epub 2020 Apr 2.
• [8] Association of vaspin gene polymorphisms with coronary artery disease in Chinese population and function study.Clin Chim Acta. 2013 Jan 16;415:233-8. doi: 10.1016/j.cca.2012.10.042. Epub 2012 Oct 31.
• [9] Insulin induces expression of the hepatic vaspin gene.Endocr J. 2020 Jan 28;67(1):9-14. doi: 10.1507/endocrj.EJ19-0276. Epub 2019 Sep 4.
• [10] 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.
• [11] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.