Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT47AK4C)

• DOT Name: Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC)
• Synonyms: hnRNP C1/C2
• Gene Name: HNRNPC
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  Lupus
  Meningioma
  Mixed connective tissue disease
  Neuroblastoma
  Non-small-cell lung cancer
  Rheumatoid arthritis
  Schizophrenia
  Stomach cancer
  Systemic lupus erythematosus
  Head-neck squamous cell carcinoma
  Adult glioblastoma
  Carcinoma of liver and intrahepatic biliary tract
  Castration-resistant prostate carcinoma
  Enterovirus infection
  Frontotemporal dementia
  Glioblastoma multiforme
  Glioma
  Hypoglycemia
  Liver cancer
  Myotonic dystrophy type 1
• UniProt ID: HNRPC_HUMAN
• PDB ID: 1TXP; 1WF2; 2MXY; 2MZ1; 3LN4
• Pfam ID: PF00076
• Sequence:
  MASNVTNKTDPRSMNSRVFIGNLNTLVVKKSDVEAIFSKYGKIVGCSVHKGFAFVQYVNE
  RNARAAVAGEDGRMIAGQVLDINLAAEPKVNRGKAGVKRSAAEMYGSVTEHPSPSPLLSS
  SFDLDYDFQRDYYDRMYSYPARVPPPPPIARAVVPSKRQRVSGNTSRRGKSGFNSKSGQR
  GSSKSGKLKGDDLQAIKKELTQIKQKVDSLLENLEKIEKEQSKQAVEMKNDKSEEEQSSS
  SVKKDETNVKMESEGGADDSAEEGDLLDDDDNEDRGDDQLELIKDDEKEAEEGEDDRDSA
  NGEDDS
• Function: Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules. Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides. May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  SUMOylation of RNA binding proteins (R-HSA-4570464)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[11]
Lupus	DISOKJWA	Strong	Biomarker	[12]
Meningioma	DISPT4TG	Strong	Altered Expression	[13]
Mixed connective tissue disease	DISXX0H8	Strong	Biomarker	[14]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[16]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[14]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[15]
Stomach cancer	DISKIJSX	Strong	Biomarker	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[17]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[18]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[19]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[20]
Enterovirus infection	DISH2UDP	Limited	Altered Expression	[21]
Frontotemporal dementia	DISKYHXL	Limited	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[18]
Glioma	DIS5RPEH	Limited	Altered Expression	[22]
Hypoglycemia	DISRCKR7	Limited	Altered Expression	[22]
Liver cancer	DISDE4BI	Limited	Altered Expression	[19]
Myotonic dystrophy type 1	DISJC0OX	Limited	Biomarker	[23]

26 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 Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[24]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[33]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[34]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[35]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[36]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[37]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[38]
Tetracaine	DM9J6C2	Approved	Tetracaine increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[47]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[49]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[50]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[51]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[52]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[41]

4 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 decreases the sumoylation of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[44]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC).	[48]

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