Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTW6B2G)

• DOT Name: Ubiquitin-associated protein 1
• Synonyms: UBAP-1; Nasopharyngeal carcinoma-associated gene 20 protein
• Gene Name: UBAP1
• Related Disease:
  Spastic paraplegia 80, autosomal dominant
  Hereditary spastic paraplegia 12
  Tourette syndrome
• UniProt ID: UBAP1_HUMAN
• PDB ID: 1WGN; 4AE4; 5LM1
• Pfam ID: PF21267
• Sequence:
  MASKKLGADFHGTFSYLDDVPFKTGDKFKTPAKVGLPIGFSLPDCLQVVREVQYDFSLEK
  KTIEWAEEIKKIEEAEREAECKIAEAEAKVNSKSGPEGDSKMSFSKTHSTATMPPPINPI
  LASLQHNSILTPTRVSSSATKQKVLSPPHIKADFNLADFECEEDPFDNLELKTIDEKEEL
  RNILVGTTGPIMAQLLDNNLPRGGSGSVLQDEEVLASLERATLDFKPLHKPNGFITLPQL
  GNCEKMSLSSKVSLPPIPAVSNIKSLSFPKLDSDDSNQKTAKLASTFHSTSCLRNGTFQN
  SLKPSTQSSASELNGHHTLGLSALNLDSGTEMPALTSSQMPSLSVLSVCTEESSPPNTGP
  TVTPPNFSVSQVPNMPSCPQAYSELQMLSPSERQCVETVVNMGYSYECVLRAMKKKGENI
  EQILDYLFAHGQLCEKGFDPLLVEEALEMHQCSEEKMMEFLQLMSKFKEMGFELKDIKEV
  LLLHNNDQDNALEDLMARAGAS
• Function: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2.
• Tissue Specificity: Ubiquitous. Highly expressed in heart, brain, placenta, lung, liver, skeletal muscle and pancreas.
• Reactome Pathway:
  Membrane binding and targetting of GAG proteins (R-HSA-174490)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  HCMV Late Events (R-HSA-9610379)
  Late endosomal microautophagy (R-HSA-9615710)
  Budding and maturation of HIV virion (R-HSA-162588)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spastic paraplegia 80, autosomal dominant	DISI9ZHZ	Strong	Autosomal dominant	[1]
Hereditary spastic paraplegia 12	DISD8CPV	Supportive	Autosomal dominant	[2]
Tourette syndrome	DISX9D54	No Known	Unknown	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ubiquitin-associated protein 1.	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ubiquitin-associated protein 1.	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ubiquitin-associated protein 1.	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ubiquitin-associated protein 1.	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ubiquitin-associated protein 1.	[8]

2 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 Ubiquitin-associated protein 1.	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ubiquitin-associated protein 1.	[10]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project. Eur J Hum Genet. 2020 Dec;28(12):1763-1768. doi: 10.1038/s41431-020-00720-w. Epub 2020 Sep 15.
• [3] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [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] 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.