Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQN3BVL)

• DOT Name: Stromal membrane-associated protein 1 (SMAP1)
• Gene Name: SMAP1
• Related Disease:
  Colorectal carcinoma
  Neoplasm
  Retinitis pigmentosa 25
• UniProt ID: SMAP1_HUMAN
• PDB ID: 2CRR
• Pfam ID: PF01412
• Sequence:
  MATRSCREKAQKLNEQHQLILSKLLREEDNKYCADCEAKGPRWASWNIGVFICIRCAGIH
  RNLGVHISRVKSVNLDQWTAEQIQCMQDMGNTKARLLYEANLPENFRRPQTDQAVEFFIR
  DKYEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKKKEEKKREKE
  PEKPAKPLTAEKLQKKDQQLEPKKSTSPKKAAEPTVDLLGLDGPAVAPVTNGNTTVPPLN
  DDLDIFGPMISNPLPATVMPPAQGTPSAPAAATLSTVTSGDLDLFTEQTTKSEEVAKKQL
  SKDSILSLYGTGTIQQQSTPGVFMGPTNIPFTSQAPAAFQGFPSMGVPVPAAPGLIGNVM
  GQSPSMMVGMPMPNGFMGNAQTGVMPLPQNVVGPQGGMVGQMGAPQSKFGLPQAQQPQWS
  LSQMNQQMAGMSISSATPTAGFGQPSSTTAGWSGSSSGQTLSTQLWK
• Function: GTPase activating protein that acts on ARF6. Plays a role in clathrin-dependent endocytosis. May play a role in erythropoiesis.
• Tissue Specificity: Detected in bone marrow, adrenal gland, trachea, lymph node, spinal cord, peripheral blood leukocytes, thyroid and stomach.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]
Retinitis pigmentosa 25	DISTIKZB	Strong	Biomarker	[2]

2 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 Stromal membrane-associated protein 1 (SMAP1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Stromal membrane-associated protein 1 (SMAP1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Stromal membrane-associated protein 1 (SMAP1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stromal membrane-associated protein 1 (SMAP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Stromal membrane-associated protein 1 (SMAP1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Stromal membrane-associated protein 1 (SMAP1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Stromal membrane-associated protein 1 (SMAP1).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Stromal membrane-associated protein 1 (SMAP1).	[9]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Stromal membrane-associated protein 1 (SMAP1).	[10]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Stromal membrane-associated protein 1 (SMAP1).	[10]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Stromal membrane-associated protein 1 (SMAP1).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Stromal membrane-associated protein 1 (SMAP1).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Stromal membrane-associated protein 1 (SMAP1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Stromal membrane-associated protein 1 (SMAP1).	[14]

References

• [1] Involvement of small ArfGAP1 (SMAP1), a novel Arf6-specific GTPase-activating protein, in microsatellite instability oncogenesis.Oncogene. 2014 May 22;33(21):2758-67. doi: 10.1038/onc.2013.211. Epub 2013 Jun 10.
• [2] Mutation screening of three candidate genes, ELOVL5, SMAP1 and GLULD1 in autosomal recessive retinitis pigmentosa.Int J Mol Med. 2005 Dec;16(6):1163-7.
• [3] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [4] 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.
• [5] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [10] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] 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.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.