Details of Drug Off-Target (DOT)

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

• DOT Name: Stromal membrane-associated protein 2 (SMAP2)
• Synonyms: Stromal membrane-associated protein 1-like
• Gene Name: SMAP2
• Related Disease:
  Asthma
  Ataxia-telangiectasia
• UniProt ID: SMAP2_HUMAN
• PDB ID: 2IQJ
• Pfam ID: PF01412
• Sequence:
  MTGKSVKDVDRYQAVLANLLLEEDNKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGV
  HISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAYLPETFRRPQIDPAVEGFIRDKYEK
  KKYMDRSLDINAFRKEKDDKWKRGSEPVPEKKLEPVVFEKVKMPQKKEDPQLPRKSSPKS
  TAPVMDLLGLDAPVACSIANSKTSNTLEKDLDLLASVPSPSSSGSRKVVGSMPTAGSAGS
  VPENLNLFPEPGSKSEEIGKKQLSKDSILSLYGSQTPQMPTQAMFMAPAQMAYPTAYPSF
  PGVTPPNSIMGSMMPPPVGMVAQPGASGMVAPMAMPAGYMGGMQASMMGVPNGMMTTQQA
  GYMAGMAAMPQTVYGVQPAQQLQWNLTQMTQQMAGMNFYGANGMMNYGQSMSGGNGQAAN
  QTLSPQMWK
• Function: GTPase activating protein that acts on ARF1. Can also activate ARF6 (in vitro). May play a role in clathrin-dependent retrograde transport from early endosomes to the trans-Golgi network.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Strong	Genetic Variation	[1]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Stromal membrane-associated protein 2 (SMAP2) affects the response to substance of Aspirin.	[1]

9 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 Stromal membrane-associated protein 2 (SMAP2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Stromal membrane-associated protein 2 (SMAP2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Stromal membrane-associated protein 2 (SMAP2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Stromal membrane-associated protein 2 (SMAP2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Stromal membrane-associated protein 2 (SMAP2).	[6]
Tibolone	DM78XFG	Approved	Tibolone increases the expression of Stromal membrane-associated protein 2 (SMAP2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Stromal membrane-associated protein 2 (SMAP2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Stromal membrane-associated protein 2 (SMAP2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Stromal membrane-associated protein 2 (SMAP2).	[10]

References

• [1] Putative association of SMAPIL polymorphisms with risk of aspirin intolerance in asthmatics. J Asthma. 2010 Nov;47(9):959-65. doi: 10.1080/02770903.2010.514637.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. Thromb Res. 2012 Jul;130(1):45-51. doi: 10.1016/j.thromres.2011.12.009. Epub 2012 Jan 2.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Putative association of SMAPIL polymorphisms with risk of aspirin intolerance in asthmatics. J Asthma. 2010 Nov;47(9):959-65. doi: 10.1080/02770903.2010.514637.