Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5UO1FA)

• DOT Name: Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD)
• Synonyms: hnRNP D0; AU-rich element RNA-binding protein 1
• Gene Name: HNRNPD
• Related Disease:
  Bone osteosarcoma
  Neoplasm
  Osteosarcoma
  Autoimmune disease
  B-cell neoplasm
  Bladder cancer
  Carcinoma of esophagus
  Cardiac failure
  Coeliac disease
  Congestive heart failure
  Crohn disease
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hepatitis C virus infection
  High blood pressure
  Idiopathic interstitial pneumonia
  Liver cancer
  Lung adenocarcinoma
  Melanoma
  Myelodysplastic syndrome
  Non-small-cell lung cancer
  Osteoarthritis
  Sarcoidosis
  Squamous cell carcinoma
  Stomach cancer
  Systemic lupus erythematosus
  Thyroid gland carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Zika virus infection
  Hepatocellular carcinoma
  Limb-girdle muscular dystrophy
  Lyme disease
  Advanced cancer
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Enterovirus infection
  Schizophrenia
  Thyroid cancer
• UniProt ID: HNRPD_HUMAN
• PDB ID: 1HD0; 1HD1; 1IQT; 1WTB; 1X0F; 2Z5N; 5IM0
• Pfam ID: PF08143 ; PF00076
• Sequence:
  MSEEQFGGDGAAAAATAAVGGSAGEQEGAMVAATQGAAAAAGSGAGTGGGTASGGTEGGS
  AESEGAKIDASKNEEDEGHSNSSPRHSEAATAQREEWKMFIGGLSWDTTKKDLKDYFSKF
  GEVVDCTLKLDPITGRSRGFGFVLFKESESVDKVMDQKEHKLNGKVIDPKRAKAMKTKEP
  VKKIFVGGLSPDTPEEKIREYFGGFGEVESIELPMDNKTNKRRGFCFITFKEEEPVKKIM
  EKKYHNVGLSKCEIKVAMSKEQYQQQQQWGSRGGFAGRARGRGGGPSQNWNQGYSNYWNQ
  GYGNYGYNSQGYGGYGGYDYTGYNNYYGYGDYSNQQSGYGKVSRRGGHQNSYKPY
• Function: Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation.
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[7]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[10]
High blood pressure	DISY2OHH	Strong	Biomarker	[6]
Idiopathic interstitial pneumonia	DISH7LPY	Strong	Altered Expression	[11]
Liver cancer	DISDE4BI	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Melanoma	DIS1RRCY	Strong	Altered Expression	[14]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[13]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[3]
Sarcoidosis	DISE5B8Z	Strong	Altered Expression	[11]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[3]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[16]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Zika virus infection	DISQUCTY	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[18]
Limb-girdle muscular dystrophy	DISI9Y1Z	moderate	Biomarker	[19]
Lyme disease	DISO70G5	moderate	Biomarker	[20]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[21]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Altered Expression	[22]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[23]
Enterovirus infection	DISH2UDP	Limited	Biomarker	[24]
Schizophrenia	DISSRV2N	Limited	Biomarker	[25]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[16]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) decreases the response to substance of Doxorubicin.	[51]
Daunorubicin	DMQUSBT	Approved	Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) affects the response to substance of Daunorubicin.	[52]

25 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 ribonucleoprotein D0 (HNRNPD).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[32]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[34]
Selenium	DM25CGV	Approved	Selenium increases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[35]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[36]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[37]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[34]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[38]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[39]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[39]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[41]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[48]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[49]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[40]

2 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 Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD).	[45]

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