Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane protein 106A (TMEM106A)
• Gene Name: TMEM106A
• Related Disease:
  Advanced cancer
  Gastric cancer
  Metastatic malignant neoplasm
  Neoplasm
  Stomach cancer
  Kidney cancer
  Renal carcinoma
• UniProt ID: T106A_HUMAN
• Pfam ID: PF07092 ; PF21002
• Sequence:
  MGKTFSQLGSWREDENKSILSSKPAIGSKAVNYSSTGSSKSFCSCVPCEGTADASFVTCP
  TCQGSGKIPQELEKQLVALIPYGDQRLKPKHTKLFVFLAVLICLVTSSFIVFFLFPRSVI
  VQPAGLNSSTVAFDEADIYLNITNILNISNGNYYPIMVTQLTLEVLHLSLVVGQVSNNLL
  LHIGPLASEQMFYAVATKIRDENTYKICTWLEIKVHHVLLHIQGTLTCSYLSHSEQLVFQ
  SYEYVDCRGNASVPHQLTPHPP
• Function: Activates macrophages and polarizes them into M1-like macrophages through the activation of the MAPK and NF-kappaB signaling pathway. Upon activation, up-regulates the expression of CD80, CD86, CD69 and MHC II on macrophages, and induces the release of pro-inflammatory cytokines such as TNF, IL1B, IL6, CCL2 and nitric oxide. May play a role in inhibition of proliferation and migration.
• Tissue Specificity: Expressed in renal cells (at protein level) . Expressed in epithelial cells .

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Posttranslational Modification	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[1]
Kidney cancer	DISBIPKM	Limited	Biomarker	[2]
Renal carcinoma	DISER9XT	Limited	Biomarker	[2]

9 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 protein 106A (TMEM106A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 106A (TMEM106A).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 106A (TMEM106A).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 106A (TMEM106A).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 106A (TMEM106A).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transmembrane protein 106A (TMEM106A).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Transmembrane protein 106A (TMEM106A).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protein 106A (TMEM106A).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 106A (TMEM106A).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transmembrane protein 106A (TMEM106A).	[11]

References

• [1] Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis.J Cell Mol Med. 2014 Aug;18(8):1655-66. doi: 10.1111/jcmm.12352. Epub 2014 Jun 28.
• [2] TMEM106A inhibits cell proliferation, migration, and induces apoptosis of lung cancer cells.J Cell Biochem. 2019 May;120(5):7825-7833. doi: 10.1002/jcb.28057. Epub 2018 Nov 19.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [9] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [10] 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.
• [11] 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.