Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT16TM3N)

• DOT Name: Splicing factor, arginine/serine-rich 19 (SCAF1)
• Synonyms: SR-related C-terminal domain-associated factor 1; SR-related and CTD-associated factor 1; SR-related-CTD-associated factor; SCAF; Serine arginine-rich pre-mRNA splicing factor SR-A1; SR-A1
• Gene Name: SCAF1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colitis
  Duchenne muscular dystrophy
  Epithelial ovarian cancer
  Hepatitis C virus infection
  Inflammatory bowel disease
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pneumonia
  Pneumonitis
  Prostate carcinoma
  Schizophrenia
  Systemic sclerosis
  Advanced cancer
  Chronic obstructive pulmonary disease
  Endometrial carcinoma
  Stroke
  Basal cell carcinoma
  Basal cell neoplasm
  Colon cancer
  Colon carcinoma
  Neoplasm
• UniProt ID: SFR19_HUMAN
• Sequence:
  MEEEDESRGKTEESGEDRGDGPPDRDPTLSPSAFILRAIQQAVGSSLQGDLPNDKDGSRC
  HGLRWRRCRSPRSEPRSQESGGTDTATVLDMATDSFLAGLVSVLDPPDTWVPSRLDLRPG
  ESEDMLELVAEVRIGDRDPIPLPVPSLLPRLRAWRTGKTVSPQSNSSRPTCARHLTLGTG
  DGGPAPPPAPSSASSSPSPSPSSSSPSPPPPPPPPAPPAPPAPRFDIYDPFHPTDEAYSP
  PPAPEQKYDPFEPTGSNPSSSAGTPSPEEEEEEEEEEEEEEEDEEEEEGLSQSISRISET
  LAGIYDDNSLSQDFPGDESPRPDAQPTQPTPAPGTPPQVDSTRADGAMRRRVFVVGTEAE
  ACREGKVSVEVVTAGGAALPPPLLPPGDSEIEEGEIVQPEEEPRLALSLFRPGGRAARPT
  PAASATPTAQPLPQPPAPRAPEGDDFLSLHAESDGEGALQVDLGEPAPAPPAADSRWGGL
  DLRRKILTQRRERYRQRSPSPAPAPAPAAAAGPPTRKKSRRERKRSGEAKEAASSSSGTQ
  PAPPAPASPWDSKKHRSRDRKPGSHASSSARRRSRSRSRSRSTRRRSRSTDRRRGGSRRS
  RSREKRRRRRRSASPPPATSSSSSSRRERHRGKHRDGGGSKKKKKRSRSRGEKRSGDGSE
  KAPAPAPPPSGSTSCGDRDSRRRGAVPPSIQDLTDHDLFAIKRTITVGRLDKSDPRGPSP
  APASSPKREVLYDSEGLSGEERGGKSSQKDRRRSGAASSSSSSREKGSRRKALDGGDRDR
  DRDRDRDRDRSSKKARPPKESAPSSGPPPKPPVSSGSGSSSSSSSCSSRKVKLQSKVAVL
  IREGVSSTTPAKDAASAGLGSIGVKFSRDRESRSPFLKPDERAPTEMAKAAPGSTKPKKT
  KVKAKAGAKKTKGTKGKTKPSKTRKKVRSGGGSGGSGGQVSLKKSKADSCSQAAGTKGAE
  ETSWSGEERAAKVPSTPPPKAAPPPPALTPDSQTVDSSCKTPEVSFLPEEATEEAGVRGG
  AEEEEEEEEEEEEEEEEEEQQPATTTATSTAAAAPSTAPSAGSTAGDSGAEDGPASRVSQ
  LPTLPPPMPWNLPAGVDCTTSGVLALTALLFKMEEANLASRAKAQELIQATNQILSHRKP
  PSSLGMTPAPVPTSLGLPPGPSSYLLPGSLPLGGCGSTPPTPTGLAATSDKREGSSSSEG
  RGDTDKYLKKLHTQERAVEEVKLAIKPYYQKKDITKEEYKDILRKAVHKICHSKSGEINP
  VKVSNLVRAYVQRYRYFRKHGRKPGDPPGPPRPPKEPGPPDKGGPGLPLPPL
• Function: May function in pre-mRNA splicing.
• Tissue Specificity: Ubiquitous. Highly expressed in fetal brain and liver, poorly expressed in salivary gland, heart, skin and ovary. Expressed in colorectal carcinomas and ovarian cancers. Overexpressed in colorectal carcinomas as compared to normal colonic mucosa.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Colitis	DISAF7DD	Strong	Altered Expression	[3]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[6]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[3]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[7]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Pneumonia	DIS8EF3M	Strong	Biomarker	[9]
Pneumonitis	DIS88E0K	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[11]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[12]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[8]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[13]
Endometrial carcinoma	DISXR5CY	moderate	Altered Expression	[14]
Stroke	DISX6UHX	moderate	Biomarker	[15]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[16]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[16]
Colon cancer	DISVC52G	Limited	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Splicing factor, arginine/serine-rich 19 (SCAF1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Splicing factor, arginine/serine-rich 19 (SCAF1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor, arginine/serine-rich 19 (SCAF1).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Splicing factor, arginine/serine-rich 19 (SCAF1).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Splicing factor, arginine/serine-rich 19 (SCAF1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Splicing factor, arginine/serine-rich 19 (SCAF1).	[23]

3 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 affects the phosphorylation of Splicing factor, arginine/serine-rich 19 (SCAF1).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Splicing factor, arginine/serine-rich 19 (SCAF1).	[22]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid affects the phosphorylation of Splicing factor, arginine/serine-rich 19 (SCAF1).	[24]

References

• [1] Prognostic significance of the expression of SR-A1, encoding a novel SR-related CTD-associated factor, in breast cancer.Biol Chem. 2006 Dec;387(12):1613-8. doi: 10.1515/BC.2006.201.
• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] SR-A1 suppresses colon inflammation and tumorigenesis through negative regulation of NF-B signaling.Biochem Pharmacol. 2018 Aug;154:335-343. doi: 10.1016/j.bcp.2018.05.017. Epub 2018 May 31.
• [4] Scavenger Receptor Class A1 Mediates Uptake of Morpholino Antisense Oligonucleotide into Dystrophic Skeletal Muscle.Mol Ther Nucleic Acids. 2019 Mar 1;14:520-535. doi: 10.1016/j.omtn.2019.01.008. Epub 2019 Jan 25.
• [5] SR-A1, a member of the human pre-mRNA splicing factor family, and its expression in colon cancer progression.Biol Chem. 2004 Sep;385(9):785-90. doi: 10.1515/BC.2004.102.
• [6] A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers.Liver Int. 2014 Apr;34(4):558-66. doi: 10.1111/liv.12330. Epub 2013 Oct 16.
• [7] Scavenger Receptor A1 Prevents Metastasis of Non-Small Cell Lung Cancer via Suppression of Macrophage Serum Amyloid A1.Cancer Res. 2017 Apr 1;77(7):1586-1598. doi: 10.1158/0008-5472.CAN-16-1569. Epub 2017 Feb 15.
• [8] Discovery and expression analysis of novel transcripts of the human SR-related CTD-associated factor 1 (SCAF1) gene in human cancer cells using Next-Generation Sequencing.Gene. 2018 Sep 5;670:155-165. doi: 10.1016/j.gene.2018.05.044. Epub 2018 May 19.
• [9] Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1).Respir Res. 2017 Feb 13;18(1):36. doi: 10.1186/s12931-017-0517-x.
• [10] Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer.Br J Cancer. 2001 Jul 20;85(2):190-8. doi: 10.1054/bjoc.2001.1885.
• [11] Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.Nat Genet. 2018 Mar;50(3):381-389. doi: 10.1038/s41588-018-0059-2. Epub 2018 Feb 26.
• [12] Efferocytosis capacities of blood monocyte-derived macrophages in systemic sclerosis.Immunol Cell Biol. 2019 Mar;97(3):340-347. doi: 10.1111/imcb.12217. Epub 2018 Dec 13.
• [13] Genetic variations in scavenger and ?adrenergic receptors and risk of pulmonary disease.Dan Med J. 2014 Sep;61(9):B4910.
• [14] Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance.Nat Commun. 2019 Sep 11;10(1):4108. doi: 10.1038/s41467-019-12124-6.
• [15] Further Evidence of the Positive Influence of Repetitive Transcranial Magnetic Stimulation on Speech and Language in Patients with Aphasia after Stroke: Results from a Double-Blind Intervention with Sham Condition.Neuropsychobiology. 2017;75(4):185-192. doi: 10.1159/000486144. Epub 2018 Jan 16.
• [16] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [17] 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.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] 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.
• [20] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] 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.
• [24] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.