Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVDHO6U)

• DOT Name: Serine/arginine-rich splicing factor 2 (SRSF2)
• Synonyms: Protein PR264; Splicing component, 35 kDa; Splicing factor SC35; SC-35; Splicing factor, arginine/serine-rich 2
• Gene Name: SRSF2
• Related Disease:
  Carcinoma
  Chronic myelomonocytic leukaemia
  Undifferentiated carcinoma
  Uveal Melanoma
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Alzheimer disease
  Amyloidosis
  Breast cancer
  Breast carcinoma
  Chronic myelomonocytic leukemia
  Essential thrombocythemia
  Hepatocellular carcinoma
  Influenza
  Lung adenocarcinoma
  Lung neoplasm
  Lung squamous cell carcinoma
  Mastocytosis
  Myeloproliferative neoplasm
  Myotonic dystrophy
  Neoplasm
  Non-small-cell lung cancer
  Osteogenesis imperfecta
  Progressive supranuclear palsy
  Supranuclear palsy, progressive, 1
  Tauopathy
  Thrombocytopenia
  Uterine cervix neoplasm
  Vitelliform macular dystrophy
  Childhood myelodysplastic syndrome
  Kidney cancer
  Lung carcinoma
  Plasma cell myeloma
  Renal carcinoma
  Systemic mastocytosis
  Triple negative breast cancer
  Myelodysplastic syndrome
  Advanced cancer
  Angioimmunoblastic T-cell Lymphoma
  Arteriosclerosis
  Atherosclerosis
  Coronary heart disease
  Human papillomavirus infection
  Intellectual disability
  Lactic acidosis
  Leigh syndrome
• UniProt ID: SRSF2_HUMAN
• PDB ID: 2KN4; 2LEA; 2LEB; 2LEC
• Pfam ID: PF00076
• Sequence:
  MSYGRPPPDVEGMTSLKVDNLTYRTSPDTLRRVFEKYGRVGDVYIPRDRYTKESRGFAFV
  RFHDKRDAEDAMDAMDGAVLDGRELRVQMARYGRPPDSHHSRRGPPPRRYGGGGYGRRSR
  SPRRRRRSRSRSRSRSRSRSRSRYSRSKSRSRTRSRSRSTSKSRSARRSKSKSSSVSRSR
  SRSRSRSRSRSPPPVSKRESKSRSRSKSPPKSPEEEGAVSS
• Function: Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. 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. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment.
• KEGG Pathway:
  Spliceosome (hsa03040)
  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

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Chronic myelomonocytic leukaemia	DISDN5P7	Definitive	Genetic Variation	[2]
Undifferentiated carcinoma	DISIAZST	Definitive	Biomarker	[1]
Uveal Melanoma	DISA7ZGL	Definitive	Genetic Variation	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[4]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Biomarker	[2]
Essential thrombocythemia	DISWWK11	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Influenza	DIS3PNU3	Strong	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[12]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[13]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[12]
Mastocytosis	DIS1TEE0	Strong	Genetic Variation	[14]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Genetic Variation	[15]
Myotonic dystrophy	DISNBEMX	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[18]
Osteogenesis imperfecta	DIS7XQSD	Strong	Genetic Variation	[19]
Progressive supranuclear palsy	DISO5KRQ	Strong	Biomarker	[20]
Supranuclear palsy, progressive, 1	DIS47BVM	Strong	Biomarker	[20]
Tauopathy	DISY2IPA	Strong	Biomarker	[21]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[22]
Uterine cervix neoplasm	DIS0BYVV	Strong	Biomarker	[23]
Vitelliform macular dystrophy	DISEFYYN	Strong	Biomarker	[24]
Childhood myelodysplastic syndrome	DISMN80I	moderate	Genetic Variation	[25]
Kidney cancer	DISBIPKM	moderate	Biomarker	[26]
Lung carcinoma	DISTR26C	moderate	Biomarker	[12]
Plasma cell myeloma	DIS0DFZ0	moderate	Genetic Variation	[27]
Renal carcinoma	DISER9XT	moderate	Biomarker	[26]
Systemic mastocytosis	DISNQ2OY	moderate	Genetic Variation	[28]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[17]
Myelodysplastic syndrome	DISYHNUI	Disputed	Genetic Variation	[29]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[30]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Limited	Genetic Variation	[31]
Arteriosclerosis	DISK5QGC	Limited	Genetic Variation	[32]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[32]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[32]
Human papillomavirus infection	DISX61LX	Limited	Altered Expression	[33]
Intellectual disability	DISMBNXP	Limited	Biomarker	[34]
Lactic acidosis	DISZI1ZK	Limited	Altered Expression	[34]
Leigh syndrome	DISWQU45	Limited	Genetic Variation	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	Serine/arginine-rich splicing factor 2 (SRSF2) decreases the response to substance of Artesunate.	[61]

22 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 2 (SRSF2).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[39]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[41]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[42]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[43]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[44]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[45]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[46]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[47]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[48]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[49]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[46]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[54]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[55]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[57]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[58]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Serine/arginine-rich splicing factor 2 (SRSF2).	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the acetylation of Serine/arginine-rich splicing factor 2 (SRSF2).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Serine/arginine-rich splicing factor 2 (SRSF2).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Serine/arginine-rich splicing factor 2 (SRSF2).	[50]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the phosphorylation of Serine/arginine-rich splicing factor 2 (SRSF2).	[59]

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 2 (SRSF2).	[56]

References

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