Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO9GMBD)

• DOT Name: RNA-binding protein 14 (RBM14)
• Synonyms: Paraspeckle protein 2; PSP2; RNA-binding motif protein 14; RRM-containing coactivator activator/modulator; Synaptotagmin-interacting protein; SYT-interacting protein
• Gene Name: RBM14
• Related Disease:
  Adult lymphoma
  Advanced cancer
  Lymphoma
  Non-small-cell lung cancer
  Pediatric lymphoma
  Adult glioblastoma
  Anxiety
  Anxiety disorder
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Depression
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Renal cell carcinoma
  Stomach cancer
  Type-1/2 diabetes
  Varicose veins
  Major depressive disorder
  Melanoma
  Nervous system disease
  Dermatomyositis
  Generalized anxiety disorder
  Metastatic malignant neoplasm
  Neuroblastoma
  Pancreatic cancer
  Small lymphocytic lymphoma
  Stroke
• UniProt ID: RBM14_HUMAN
• PDB ID: 2DNP
• Pfam ID: PF00076
• Sequence:
  MKIFVGNVDGADTTPEELAALFAPYGTVMSCAVMKQFAFVHMRENAGALRAIEALHGHEL
  RPGRALVVEMSRPRPLNTWKIFVGNVSAACTSQELRSLFERRGRVIECDVVKDYAFVHME
  KEADAKAAIAQLNGKEVKGKRINVELSTKGQKKGPGLAVQSGDKTKKPGAGDTAFPGTGG
  FSATFDYQQAFGNSTGGFDGQARQPTPPFFGRDRSPLRRSPPRASYVAPLTAQPATYRAQ
  PSVSLGAAYRAQPSASLGVGYRTQPMTAQAASYRAQPSVSLGAPYRGQLASPSSQSAAAS
  SLGPYGGAQPSASALSSYGGQAAAASSLNSYGAQGSSLASYGNQPSSYGAQAASSYGVRA
  AASSYNTQGAASSLGSYGAQAASYGAQSAASSLAYGAQAASYNAQPSASYNAQSAPYAAQ
  QAASYSSQPAAYVAQPATAAAYASQPAAYAAQATTPMAGSYGAQPVVQTQLNSYGAQASM
  GLSGSYGAQSAAAATGSYGAAAAYGAQPSATLAAPYRTQSSASLAASYAAQQHPQAAASY
  RGQPGNAYDGAGQPSAAYLSMSQGAVANANSTPPPYERTRLSPPRASYDDPYKKAVAMSK
  RYGSDRRLAELSDYRRLSESQLSFRRSPTKSSLDYRRLPDAHSDYARYSGSYNDYLRAAQ
  MHSGYQRRM
• Function: Isoform 1 may function as a nuclear receptor coactivator, enhancing transcription through other coactivators such as NCOA6 and CITED1. Isoform 2, functions as a transcriptional repressor, modulating transcriptional activities of coactivators including isoform 1, NCOA6 and CITED1. Regulates centriole biogenesis by suppressing the formation of aberrant centriolar protein complexes in the cytoplasm and thus preserving mitotic spindle integrity. Prevents the formation of the STIL-CENPJ complex (which can induce the formation of aberrant centriolar protein complexes) by interfering with the interaction of STIL with CENPJ. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. Also involved in the regulation of pre-mRNA alternative splicing.
• Tissue Specificity: Expressed in all tissues tested, including brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood lymphocytes.
• Reactome Pathway: RUNX2 regulates bone development (R-HSA-8941326)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Lymphoma	DISN6V4S	Definitive	Genetic Variation	[1]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Genetic Variation	[1]
Pediatric lymphoma	DIS51BK2	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Anxiety	DISIJDBA	Strong	Biomarker	[3]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[6]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[6]
Depression	DIS3XJ69	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[11]
Varicose veins	DISIMBN2	Strong	Biomarker	[12]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[13]
Melanoma	DIS1RRCY	moderate	Biomarker	[14]
Nervous system disease	DISJ7GGT	Disputed	Biomarker	[15]
Dermatomyositis	DIS50C5O	Limited	Biomarker	[16]
Generalized anxiety disorder	DISPSQCW	Limited	Genetic Variation	[13]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[17]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[18]
Pancreatic cancer	DISJC981	Limited	Biomarker	[19]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[20]
Stroke	DISX6UHX	Limited	Biomarker	[21]

20 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 RNA-binding protein 14 (RBM14).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RNA-binding protein 14 (RBM14).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA-binding protein 14 (RBM14).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RNA-binding protein 14 (RBM14).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RNA-binding protein 14 (RBM14).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein 14 (RBM14).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of RNA-binding protein 14 (RBM14).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of RNA-binding protein 14 (RBM14).	[29]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of RNA-binding protein 14 (RBM14).	[30]
Selenium	DM25CGV	Approved	Selenium increases the expression of RNA-binding protein 14 (RBM14).	[31]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of RNA-binding protein 14 (RBM14).	[32]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of RNA-binding protein 14 (RBM14).	[33]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of RNA-binding protein 14 (RBM14).	[34]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein 14 (RBM14).	[35]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of RNA-binding protein 14 (RBM14).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of RNA-binding protein 14 (RBM14).	[36]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RNA-binding protein 14 (RBM14).	[37]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of RNA-binding protein 14 (RBM14).	[40]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of RNA-binding protein 14 (RBM14).	[41]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of RNA-binding protein 14 (RBM14).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of RNA-binding protein 14 (RBM14).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RNA-binding protein 14 (RBM14).	[39]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of RNA-binding protein 14 (RBM14).	[39]

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