Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5500CF)

• DOT Name: Secreted and transmembrane protein 1 (SECTM1)
• Synonyms: Protein K-12
• Gene Name: SECTM1
• Related Disease:
  Meesmann corneal dystrophy
  Macular corneal dystrophy
• UniProt ID: SCTM1_HUMAN
• Sequence:
  MQTCPLAFPGHVSQALGTLLFLAASLSAQNEGWDSPICTEGVVSVSWGENTVMSCNISNA
  FSHVNIKLRAHGQESAIFNEVAPGYFSRDGWQLQVQGGVAQLVIKGARDSHAGLYMWHLV
  GHQRNNRQVTLEVSGAEPQSAPDTGFWPVPAVVTAVFILLVALVMFAWYRCRCSQQRREK
  KFFLLEPQMKVAALRAGAQQGLSRASAELWTPDSEPTPRPLALVFKPSPLGALELLSPQP
  LFPYAADP
• Function: May be involved in thymocyte signaling.
• Tissue Specificity: Detected at the highest levels in peripheral blood leukocytes and breast cancer cell lines. Found in leukocytes of the myeloid lineage, with the strongest expression observed in granulocytes and no detectable expression in lymphocytes. Expressed in thymic epithelial cells and fibroblasts.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meesmann corneal dystrophy	DISJFWTC	moderate	Genetic Variation	[1]
Macular corneal dystrophy	DISOLD0H	Limited	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 Secreted and transmembrane protein 1 (SECTM1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Secreted and transmembrane protein 1 (SECTM1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Secreted and transmembrane protein 1 (SECTM1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[7]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[8]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Secreted and transmembrane protein 1 (SECTM1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Secreted and transmembrane protein 1 (SECTM1).	[11]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Secreted and transmembrane protein 1 (SECTM1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Secreted and transmembrane protein 1 (SECTM1).	[14]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Secreted and transmembrane protein 1 (SECTM1).	[12]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Secreted and transmembrane protein 1 (SECTM1).	[15]

References

• [1] A novel mutation in KRT12 associated with Meesmann's epithelial corneal dystrophy.Br J Ophthalmol. 2002 Jul;86(7):729-32. doi: 10.1136/bjo.86.7.729.
• [2] A novel keratin 12 mutation in a German kindred with Meesmann's corneal dystrophy.Br J Ophthalmol. 2000 May;84(5):527-30. doi: 10.1136/bjo.84.5.527.
• [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] 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.
• [5] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [8] 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.
• [9] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.