Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWSFC2F)

• DOT Name: Small integral membrane protein 1 (SMIM1)
• Synonyms: Vel blood group antigen
• Gene Name: SMIM1
• Related Disease:
  Hyperglycemia
  Hepatitis C virus infection
  Liver cirrhosis
• UniProt ID: SMIM1_HUMAN
• Pfam ID: PF15875
• Sequence:
  MQPQESHVHYSRWEDGSRDGVSLGAVSSTEEASRCRRISQRLCTGKLGIAMKVLGGVALF
  WIIFILGYLTGYYVHKCK
• Function: Regulator of red blood cell formation.
• Tissue Specificity: Highly expressed in the bone marrow and expressed at lower levels in non-hematopoietic tissues. Highly expressed in erythroleukemia cell lines. Up-regulated in CD34+ hematopoietic progenitors cultured toward red blood cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[2]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[2]

3 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 Small integral membrane protein 1 (SMIM1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Small integral membrane protein 1 (SMIM1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Small integral membrane protein 1 (SMIM1).	[9]

4 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 integral membrane protein 1 (SMIM1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small integral membrane protein 1 (SMIM1).	[5]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Small integral membrane protein 1 (SMIM1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Small integral membrane protein 1 (SMIM1).	[8]

References

• [1] Sofosbuvir/velpatasvir for 12weeks in genotype 1-4 HCV-infected liver transplant recipients.J Hepatol. 2018 Sep;69(3):603-607. doi: 10.1016/j.jhep.2018.05.039. Epub 2018 Jun 8.
• [2] Real-world effectiveness and safety of sofosbuvir/velpatasvir and ledipasvir/sofosbuvir hepatitis C treatment in a single centre in Germany.PLoS One. 2019 Apr 4;14(4):e0214795. doi: 10.1371/journal.pone.0214795. eCollection 2019.
• [3] 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.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [7] 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.
• [8] 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.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.