Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN3HZYF)

• DOT Name: Protein BUD31 homolog (BUD31)
• Synonyms: Protein EDG-2; Protein G10 homolog
• Gene Name: BUD31
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Breast carcinoma
  Breast neoplasm
  Charcot marie tooth disease
  Epithelial ovarian cancer
  Knee osteoarthritis
  Metastatic malignant neoplasm
  Osteoarthritis
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: BUD31_HUMAN
• PDB ID: 4OED; 4OH6; 4OKB; 5MQF; 5XJC; 5YZG; 5Z56; 5Z57; 6FF4; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6ZYM; 7AAV; 7ABF; 7ABG; 7ABI; 7QTT; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF01125
• Sequence:
  MPKVKRSRKAPPDGWELIEPTLDELDQKMREAETEPHEGKRKVESLWPIFRIHHQKTRYI
  FDLFYKRKAISRELYEYCIKEGYADKNLIAKWKKQGYENLCCLRCIQTRDTNFGTNCICR
  VPKSKLEVGRIIECTHCGCRGCSG
• Function: Involved in the pre-mRNA splicing process. May play a role as regulator of AR transcriptional activity; may increase AR transcriptional activity.
• Tissue Specificity: Detected in epithelial and stromal cells in benign prostate hyperplasia tissue (at protein level).
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[3]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[7]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[9]
Neoplasm	DISZKGEW	Disputed	Biomarker	[10]

14 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 Protein BUD31 homolog (BUD31).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein BUD31 homolog (BUD31).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein BUD31 homolog (BUD31).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein BUD31 homolog (BUD31).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein BUD31 homolog (BUD31).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein BUD31 homolog (BUD31).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein BUD31 homolog (BUD31).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein BUD31 homolog (BUD31).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein BUD31 homolog (BUD31).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein BUD31 homolog (BUD31).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein BUD31 homolog (BUD31).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein BUD31 homolog (BUD31).	[23]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein BUD31 homolog (BUD31).	[24]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Protein BUD31 homolog (BUD31).	[25]

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 affects the methylation of Protein BUD31 homolog (BUD31).	[19]

References

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• [2] Differential stimulation of signaling pathways initiated by Edg-2 in response to lysophosphatidic acid or sphingosine-1-phosphate.Cell Mol Life Sci. 2000 Jul;57(7):1109-16. doi: 10.1007/PL00000747.
• [3] Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2.Cancer Res. 2007 Dec 15;67(24):11751-9. doi: 10.1158/0008-5472.CAN-07-3175.
• [4] Edg-2 in myelin-forming cells: isoforms, genomic mapping, and exclusion in Charcot-Marie-Tooth disease.Glia. 1999 Apr;26(2):176-85. doi: 10.1002/(sici)1098-1136(199904)26:2<176::aid-glia8>3.0.co;2-k.
• [5] Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer.Cancer Res. 1999 Oct 15;59(20):5370-5.
• [6] A functional SNP in EDG2 increases susceptibility to knee osteoarthritis in Japanese.Hum Mol Genet. 2008 Jun 15;17(12):1790-7. doi: 10.1093/hmg/ddn069. Epub 2008 Mar 6.
• [7] Testing the druggable endothelial differentiation gene 2 knee osteoarthritis genetic factor for replication in a wide range of sample collections.Ann Rheum Dis. 2009 Jun;68(6):1017-21. doi: 10.1136/ard.2008.093641. Epub 2008 Jul 14.
• [8] New Insights into the Binding Mechanism of Co-regulator BUD31 to AR AF2 Site: Structural Determination and Analysis of the Mutation Effect.Curr Comput Aided Drug Des. 2020;16(1):45-53. doi: 10.2174/1573409915666190502153307.
• [9] EDG2 enhanced the progression of hepatocellular carcinoma by LPA/PI3K/AKT/ mTOR signaling.Oncotarget. 2017 Aug 2;8(39):66154-66168. doi: 10.18632/oncotarget.19825. eCollection 2017 Sep 12.
• [10] Nm23-H1 suppresses tumor cell motility by down-regulating the lysophosphatidic acid receptor EDG2.Cancer Res. 2007 Aug 1;67(15):7238-46. doi: 10.1158/0008-5472.CAN-07-0962.
• [11] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [12] 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.
• [13] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [17] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] 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.
• [21] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [22] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [25] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.