Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF61HOV)

• DOT Name: Serine/arginine-rich splicing factor 1 (SRSF1)
• Synonyms: Alternative-splicing factor 1; ASF-1; Splicing factor, arginine/serine-rich 1; pre-mRNA-splicing factor SF2, P33 subunit
• Gene Name: SRSF1
• Related Disease:
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  Lung neoplasm
  Prostate cancer
  Prostate carcinoma
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Carcinoma of liver and intrahepatic biliary tract
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  HIV infectious disease
  Inflammatory bowel disease
  Influenza
  Liver cancer
  Metastatic malignant neoplasm
  Multiple sclerosis
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Progressive multifocal leukoencephalopathy
  Sarcoma
  Squamous cell carcinoma
  Stomach cancer
  Systemic lupus erythematosus
  Tuberculosis
  Autoimmune disease
  Breast carcinoma
  Congenital myasthenic syndrome
  Lung adenocarcinoma
  Schizophrenia
  Arteriosclerosis
  Atherosclerosis
  Bone osteosarcoma
  Coronary heart disease
  Lung cancer
  Lung carcinoma
  Neuroblastoma
  Osteosarcoma
• UniProt ID: SRSF1_HUMAN
• PDB ID: 1X4A; 2M7S; 2M8D; 2O3D; 3BEG; 4C0O; 6HPJ; 7ABG
• Pfam ID: PF00076
• Sequence:
  MSGGGVIRGPAGNNDCRIYVGNLPPDIRTKDIEDVFYKYGAIRDIDLKNRRGGPPFAFVE
  FEDPRDAEDAVYGRDGYDYDGYRLRVEFPRSGRGTGRGGGGGGGGGAPRGRYGPPSRRSE
  NRVVVSGLPPSGSWQDLKDHMREAGDVCYADVYRDGTGVVEFVRKEDMTYAVRKLDNTKF
  RSHEGETAYIRVKVDGPRSPSYGRSRSRSRSRSRSRSRSNSRSRSYSPRRSRGSPRYSPR
  HSRSRSRT
• Function: Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway.
• KEGG Pathway:
  Spliceosome (hsa03040)
  IL-17 sig.ling pathway (hsa04657)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  mRNA 3'-end processing (R-HSA-72187)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Altered Expression	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Posttranslational Modification	[2]
Lung neoplasm	DISVARNB	Definitive	Altered Expression	[3]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
HIV infectious disease	DISO97HC	Strong	Biomarker	[17]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[18]
Influenza	DIS3PNU3	Strong	Biomarker	[19]
Liver cancer	DISDE4BI	Strong	Biomarker	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[20]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[23]
Obesity	DIS47Y1K	Strong	Biomarker	[24]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[25]
Sarcoma	DISZDG3U	Strong	Altered Expression	[26]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[27]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[28]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[29]
Autoimmune disease	DISORMTM	moderate	Biomarker	[28]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[1]
Congenital myasthenic syndrome	DISJLG2T	moderate	Genetic Variation	[30]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[31]
Schizophrenia	DISSRV2N	moderate	Biomarker	[32]
Arteriosclerosis	DISK5QGC	Limited	Genetic Variation	[33]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[33]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[34]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[33]
Lung cancer	DISCM4YA	Limited	Biomarker	[35]
Lung carcinoma	DISTR26C	Limited	Biomarker	[35]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[36]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Serine/arginine-rich splicing factor 1 (SRSF1) affects the response to substance of Mitomycin.	[65]

29 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 Serine/arginine-rich splicing factor 1 (SRSF1).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[43]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[44]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[46]
Selenium	DM25CGV	Approved	Selenium increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[47]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[42]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[48]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[49]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[50]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[51]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[52]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[42]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[54]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[56]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[59]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[60]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[62]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[63]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Serine/arginine-rich splicing factor 1 (SRSF1).	[64]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Serine/arginine-rich splicing factor 1 (SRSF1).	[58]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Paraquat	DMR8O3X	Investigative	Paraquat affects the localization of Serine/arginine-rich splicing factor 1 (SRSF1).	[61]

References

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