Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR4RO3N)

• DOT Name: Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1)
• Synonyms: Dendritic cell-derived ubiquitin-like protein; DULP; Hepatocyte odd protein shuttling protein; Ubiquitin-like protein SB144
• Gene Name: TMUB1
• Related Disease:
  Arthrogryposis, renal dysfunction, and cholestasis 1
  Hepatocellular carcinoma
  Neoplasm
  Salmonella infection
  Skin pigmentation disorder
  Advanced cancer
• UniProt ID: TMUB1_HUMAN
• Pfam ID: PF00240
• Sequence:
  MTLIEGVGDEVTVLFSVLACLLVLALAWVSTHTAEGGDPLPQPSGTPTPSQPSAAMAATD
  SMRGEAPGAETPSLRHRGQAAQPEPSTGFTATPPAPDSPQEPLVLRLKFLNDSEQVARAW
  PHDTIGSLKRTQFPGREQQVRLIYQGQLLGDDTQTLGSLHLPPNCVLHCHVSTRVGPPNP
  PCPPGSEPGPSGLEIGSLLLPLLLLLLLLLWYCQIQYRPFFPLTATLGLAGFTLLLSLLA
  FAMYRP
• Function: Involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR. Involved in positive regulation of AMPA-selective glutamate receptor GRIA2 recycling to the cell surface. Acts as a negative regulator of hepatocyte growth during regeneration; [iHOPS]: May contribute to the regulation of translation during cell-cycle progression. May contribute to the regulation of cell proliferation. May be involved in centrosome assembly. Modulates stabilization and nucleolar localization of tumor suppressor CDKN2A and enhances association between CDKN2A and NPM1.
• Tissue Specificity: Ubiquitously expressed with highest levels in mammary and thyroid glands, bone marrow and spleen; limited expression in cardiac, pancreatic and ovarian tissues.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthrogryposis, renal dysfunction, and cholestasis 1	DISRS2RG	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Salmonella infection	DISTJ434	Strong	Biomarker	[4]
Skin pigmentation disorder	DIS3BXY0	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1).	[9]

References

• [1] CORVET, CHEVI and HOPS - multisubunit tethers of the endo-lysosomal system in health and disease.J Cell Sci. 2019 May 15;132(10):jcs189134. doi: 10.1242/jcs.189134.
• [2] Transmembrane and Ubiquitin-Like Domain Containing 1 Protein (TMUB1) Negatively Regulates Hepatocellular Carcinoma Proliferation via Regulating Signal Transducer and Activator of Transcription 1 (STAT1).Med Sci Monit. 2019 Dec 12;25:9471-9482. doi: 10.12659/MSM.920319.
• [3] Microarray analysis reveals Tmub1 as a cell cycle-associated protein in rat hepatocytes.Mol Med Rep. 2018 Mar;17(3):4337-4344. doi: 10.3892/mmr.2018.8451. Epub 2018 Jan 17.
• [4] Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication.PLoS Pathog. 2017 Oct 30;13(10):e1006700. doi: 10.1371/journal.ppat.1006700. eCollection 2017 Oct.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] 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.
• [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.
• [10] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.