Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPQEFR0)

• DOT Name: Transmembrane protein 54 (TMEM54)
• Synonyms: Beta-casein-like protein; Protein CAC-1
• Gene Name: TMEM54
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Coronary heart disease
  Dementia
  Follicular lymphoma
  Myocardial infarction
  Stroke
  Cardiovascular disease
  High blood pressure
  Type-1/2 diabetes
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Colorectal adenoma
  Colorectal carcinoma
  Neoplasm
• UniProt ID: TMM54_HUMAN
• Pfam ID: PF12304
• Sequence:
  MCLRLGGLSVGDFRKVLMKTGLVLVVLGHVSFITAALFHGTVLRYVGTPQDAVALQYCVV
  NILSVTSAIVVITSGIAAIVLSRYLPSTPLRWTVFSSSVACALLSLTCALGLLASIAMTF
  ATQGKALLAACTFGSSELLALAPDCPFDPTRIYSSSLCLWGIALVLCVAENVFAVRCAQL
  THQLLELRPWWGKSSHHMMRENPELVEGRDLLSCTSSEPLTL
• Tissue Specificity: Ubiquitously expressed in cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[4]
Dementia	DISXL1WY	Strong	Biomarker	[5]
Follicular lymphoma	DISVEUR6	Strong	Altered Expression	[1]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[6]
Stroke	DISX6UHX	Strong	Genetic Variation	[6]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[7]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[8]
Type-1/2 diabetes	DISIUHAP	Disputed	Genetic Variation	[9]
Breast cancer	DIS7DPX1	Limited	Biomarker	[10]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[10]
Cervical cancer	DISFSHPF	Limited	Biomarker	[11]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[11]
Colorectal adenoma	DISTSVHM	Limited	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[13]
Neoplasm	DISZKGEW	Limited	Altered Expression	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transmembrane protein 54 (TMEM54).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 54 (TMEM54).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 54 (TMEM54).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 54 (TMEM54).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 54 (TMEM54).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transmembrane protein 54 (TMEM54).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transmembrane protein 54 (TMEM54).	[21]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transmembrane protein 54 (TMEM54).	[22]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transmembrane protein 54 (TMEM54).	[21]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Transmembrane protein 54 (TMEM54).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane protein 54 (TMEM54).	[24]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transmembrane protein 54 (TMEM54).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 54 (TMEM54).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transmembrane protein 54 (TMEM54).	[26]

References

• [1] Expression of bcl-2 protein in stage T1N0M0 non-small cell lung carcinoma.Hum Pathol. 1995 Nov;26(11):1227-32. doi: 10.1016/0046-8177(95)90198-1.
• [2] Coronary artery calcium and the competing long-term risk of cardiovascular vs. cancer mortality: the CAC Consortium.Eur Heart J Cardiovasc Imaging. 2019 Apr 1;20(4):389-395. doi: 10.1093/ehjci/jey176.
• [3] Expression of the newly identified gene CAC1 in the hippocampus of Alzheimer's disease patients.J Mol Neurosci. 2012 Jun;47(2):207-18. doi: 10.1007/s12031-012-9717-5. Epub 2012 Mar 14.
• [4] Predictors of Severe or Moderate Coronary Artery Disease in Asymptomatic Individuals with Extremely Low Coronary Calcium Scores.Yonsei Med J. 2019 Jul;60(7):619-625. doi: 10.3349/ymj.2019.60.7.619.
• [5] Coronary Artery Calcium and Risk of Dementia in MESA (Multi-Ethnic Study of Atherosclerosis).Circ Cardiovasc Imaging. 2017 May;10(5):e005349. doi: 10.1161/CIRCIMAGING.116.005349.
• [6] Coronary Artery Calcium and Long-TermRisk of Death, MyocardialInfarction, and Stroke: The Walter Reed Cohort Study.JACC Cardiovasc Imaging. 2018 Dec;11(12):1799-1806. doi: 10.1016/j.jcmg.2017.09.003. Epub 2017 Nov 15.
• [7] All-cause and cause-specific mortality in individuals with zero and minimal coronary artery calcium: A long-term, competing risk analysis in the Coronary Artery Calcium Consortium.Atherosclerosis. 2020 Feb;294:72-79. doi: 10.1016/j.atherosclerosis.2019.11.008. Epub 2019 Nov 16.
• [8] Relation of Coronary Artery Calcium and Extra-Coronary Aortic Calcium to Incident Hypertension (from the Multi-Ethnic Study of Atherosclerosis).Am J Cardiol. 2018 Jan 15;121(2):210-216. doi: 10.1016/j.amjcard.2017.10.018. Epub 2017 Oct 24.
• [9] Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort.J Diabetes Complications. 2019 Sep;33(9):616-622. doi: 10.1016/j.jdiacomp.2019.05.015. Epub 2019 May 30.
• [10] Negative regulation of ER by a novel protein CAC1 through association with histone demethylase LSD1.FEBS Lett. 2013 Jan 4;587(1):17-22. doi: 10.1016/j.febslet.2012.10.054. Epub 2012 Nov 20.
• [11] Specific detection of circulating tumor cells by reverse transcriptase-polymerase chain reaction of a beta-casein-like protein, preferentially expressed in malignant neoplasms.Anticancer Res. 2001 Jul-Aug;21(4A):2547-51.
• [12] Coexistence of Colorectal Adenomas and Coronary Calcification in Asymptomatic Men and Women.J Clin Gastroenterol. 2018 Jul;52(6):508-514. doi: 10.1097/MCG.0000000000000824.
• [13] CAC1 knockdown reverses drug resistance through the downregulation of P-gp and MRP-1 expression in colorectal cancer.PLoS One. 2019 Sep 10;14(9):e0222035. doi: 10.1371/journal.pone.0222035. eCollection 2019.
• [14] DNA methylation changes involved in the tumor increase in F2 males born to gestationally arsenite-exposed F1 male mice.Cancer Sci. 2019 Aug;110(8):2629-2642. doi: 10.1111/cas.14104. Epub 2019 Jul 25.
• [15] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [16] 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.
• [17] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [18] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [19] 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.
• [20] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [21] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [22] 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.
• [23] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [24] 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.
• [25] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [26] 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.
• [27] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.