Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRMF2WY)

• DOT Name: Pre-mRNA-splicing factor SPF27 (BCAS2)
• Synonyms: Breast carcinoma-amplified sequence 2; DNA amplified in mammary carcinoma 1 protein; Spliceosome-associated protein SPF 27
• Gene Name: BCAS2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Autism
  Breast neoplasm
  Carcinoma of esophagus
  Esophageal cancer
  Estrogen-receptor positive breast cancer
  Neoplasm of esophagus
  B-cell lymphoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SPF27_HUMAN
• PDB ID: 5MQF; 5XJC; 5YZG; 5Z56; 5Z57; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 7A5P; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF05700
• Sequence:
  MAGTGLVAGEVVVDALPYFDQGYEAPGVREAAAALVEEETRRYRPTKNYLSYLTAPDYSA
  FETDIMRNEFERLAARQPIELLSMKRYELPAPSSGQKNDITAWQECVNNSMAQLEHQAVR
  IENLELMSQHGCNAWKVYNENLVHMIEHAQKELQKLRKHIQDLNWQRKNMQLTAGSKLRE
  MESNWVSLVSKNYEIERTIVQLENEIYQIKQQHGEANKENIRQDF
• Function: Required for pre-mRNA splicing as component of the activated spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR).
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[1]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[7]
Prostate cancer	DISF190Y	Limited	Altered Expression	[8]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[8]

10 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 Pre-mRNA-splicing factor SPF27 (BCAS2).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[15]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[16]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Pre-mRNA-splicing factor SPF27 (BCAS2).	[18]

References

• [1] BCAS2 Enhances Carcinogenic Effects of Estrogen Receptor Alpha in Breast Cancer Cells.Int J Mol Sci. 2019 Feb 22;20(4):966. doi: 10.3390/ijms20040966.
• [2] Breast cancer amplified sequence 2, a novel negative regulator of the p53 tumor suppressor.Cancer Res. 2009 Dec 1;69(23):8877-85. doi: 10.1158/0008-5472.CAN-09-2023. Epub 2009 Nov 10.
• [3] Common genetic variants on 1p13.2 associate with risk of autism.Mol Psychiatry. 2014 Nov;19(11):1212-9. doi: 10.1038/mp.2013.146. Epub 2013 Nov 5.
• [4] Potentiation of estrogen receptor transcriptional activity by breast cancer amplified sequence 2.Biochem Biophys Res Commun. 2005 Mar 11;328(2):393-8. doi: 10.1016/j.bbrc.2004.12.187.
• [5] miR-486 functions as a tumor suppressor in esophageal cancer by targeting CDK4/BCAS2.Oncol Rep. 2018 Jan;39(1):71-80. doi: 10.3892/or.2017.6064. Epub 2017 Nov 1.
• [6] Novel IGH and MYC Translocation Partners in Diffuse Large B-Cell Lymphomas.Genes Chromosomes Cancer. 2016 Dec;55(12):932-943. doi: 10.1002/gcc.22391. Epub 2016 Jul 12.
• [7] Amplification of the BCAS2 gene at chromosome 1p13.3-21 in human primary breast cancer.Cancer Lett. 2002 Nov 28;185(2):219-23. doi: 10.1016/s0304-3835(02)00286-0.
• [8] BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability.Br J Cancer. 2015 Jan 20;112(2):391-402. doi: 10.1038/bjc.2014.603. Epub 2014 Dec 2.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Proteasome inhibition creates a chromatin landscape favorable to RNA Pol II processivity. J Biol Chem. 2020 Jan 31;295(5):1271-1287. doi: 10.1074/jbc.RA119.011174. Epub 2019 Dec 5.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.