Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRXDL86)

• DOT Name: Transmembrane and coiled-coil domains protein 1 (TMCC1)
• Gene Name: TMCC1
• UniProt ID: TMCC1_HUMAN
• Pfam ID: PF10267
• Sequence:
  MEPSGSEQLFEDPDPGGKSQDAEARKQTESEQKLSKMTHNALENINVIGQGLKHLFQHQR
  RRSSVSPHDVQQIQADPEPEMDLESQNACAEIDGVPTHPTALNRVLQQIRVPPKMKRGTS
  LHSRRGKPEAPKGSPQINRKSGQEMTAVMQSGRPRSSSTTDAPTSSAMMEIACAAAAAAA
  ACLPGEEGTAERIERLEVSSLAQTSSAVASSTDGSIHTDSVDGTPDPQRTKAAIAHLQQK
  ILKLTEQIKIAQTARDDNVAEYLKLANSADKQQAARIKQVFEKKNQKSAQTILQLQKKLE
  HYHRKLREVEQNGIPRQPKDVFRDMHQGLKDVGAKVTGFSEGVVDSVKGGFSSFSQATHS
  AAGAVVSKPREIASLIRNKFGSADNIPNLKDSLEEGQVDDAGKALGVISNFQSSPKYGSE
  EDCSSATSGSVGANSTTGGIAVGASSSKTNTLDMQSSGFDALLHEIQEIRETQARLEESF
  ETLKEHYQRDYSLIMQTLQEERYRCERLEEQLNDLTELHQNEILNLKQELASMEEKIAYQ
  SYERARDIQEALEACQTRISKMELQQQQQQVVQLEGLENATARNLLGKLINILLAVMAVL
  LVFVSTVANCVVPLMKTRNRTFSTLFLVVFIAFLWKHWDALFSYVERFFSSPR
• Function: Endoplasmic reticulum membrane protein that promotes endoplasmic reticulum-associated endosome fission. Localizes to contact sites between the endoplasmic reticulum and endosomes and acts by promoting recruitment of the endoplasmic reticulum to endosome tubules for fission. Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[9]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[10]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[17]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[6]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Transmembrane and coiled-coil domains protein 1 (TMCC1).	[18]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] 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.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [11] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [18] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.