Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUTZH0W)

• DOT Name: Signal-transducing adaptor protein 1 (STAP1)
• Synonyms: STAP-1; BCR downstream-signaling protein 1; Docking protein BRDG1; Stem cell adaptor protein 1
• Gene Name: STAP1
• Related Disease:
  Acute lymphocytic leukaemia
  Familial hypercholesterolemia
  Hypercholesterolemia, familial, 1
  Homozygous familial hypercholesterolemia
  Uveal Melanoma
• UniProt ID: STAP1_HUMAN
• PDB ID: 1X1F; 3MAZ
• Pfam ID: PF00169 ; PF00017
• Sequence:
  MMAKKPPKPAPRRIFQERLKITALPLYFEGFLLIKRSGYREYEHYWTELRGTTLFFYTDK
  KSIIYVDKLDIVDLTCLTEQNSTEKNCAKFTLVLPKEEVQLKTENTESGEEWRGFILTVT
  ELSVPQNVSLLPGQVIKLHEVLEREKKRRIETEQSTSVEKEKEPTEDYVDVLNPMPACFY
  TVSRKEATEMLQKNPSLGNMILRPGSDSRNYSITIRQEIDIPRIKHYKVMSVGQNYTIEL
  EKPVTLPNLFSVIDYFVKETRGNLRPFICSTDENTGQEPSMEGRSEKLKKNPHIA
• Function: In BCR signaling, appears to function as a docking protein acting downstream of TEC and participates in a positive feedback loop by increasing the activity of TEC.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[1]
Familial hypercholesterolemia	DISC06IX	Strong	Biomarker	[2]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Biomarker	[2]
Homozygous familial hypercholesterolemia	DISRCNCF	moderate	Genetic Variation	[3]
Uveal Melanoma	DISA7ZGL	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Signal-transducing adaptor protein 1 (STAP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Signal-transducing adaptor protein 1 (STAP1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Signal-transducing adaptor protein 1 (STAP1).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Signal-transducing adaptor protein 1 (STAP1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Signal-transducing adaptor protein 1 (STAP1).	[11]

2 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 increases the methylation of Signal-transducing adaptor protein 1 (STAP1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Signal-transducing adaptor protein 1 (STAP1).	[10]

References

• [1] High STAP1 expression in DUX4-rearranged cases is not suitable as therapeutic target in pediatric B-cell precursor acute lymphoblastic leukemia.Sci Rep. 2018 Jan 12;8(1):693. doi: 10.1038/s41598-017-17704-4.
• [2] Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia.Atherosclerosis. 2020 Jan;292:143-151. doi: 10.1016/j.atherosclerosis.2019.11.025. Epub 2019 Nov 29.
• [3] Alirocumab efficacy in patients with double heterozygous, compound heterozygous, or homozygous familial hypercholesterolemia.J Clin Lipidol. 2018 Mar-Apr;12(2):390-396.e8. doi: 10.1016/j.jacl.2017.12.008. Epub 2017 Dec 28.
• [4] Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.Melanoma Res. 2020 Apr;30(2):166-172. doi: 10.1097/CMR.0000000000000641.
• [5] 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.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] 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.
• [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.
• [11] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.