Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIRPN6B)

• DOT Name: Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1)
• Synonyms: hnRNP A1; Helix-destabilizing protein; Single-strand RNA-binding protein; hnRNP core protein A1
• Gene Name: HNRNPA1
• Related Disease:
  Amyotrophic lateral sclerosis type 20
  Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3
  Amyotrophic lateral sclerosis
  Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
• UniProt ID: ROA1_HUMAN
• PDB ID: 1HA1; 1L3K; 1PGZ; 1PO6; 1U1K; 1U1L; 1U1M; 1U1N; 1U1O; 1U1P; 1U1Q; 1U1R; 1UP1; 2H4M; 2LYV; 2UP1; 4YOE; 5MPG; 5MPL; 5ZGD; 5ZGL; 6BXX; 6DCL; 6J60; 7BX7; 7ZJ2
• Pfam ID: PF11627 ; PF00076
• Sequence:
  MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCVVMRDPNTKRSRGFGFV
  TYATVEEVDAAMNARPHKVDGRVVEPKRAVSREDSQRPGAHLTVKKIFVGGIKEDTEEHH
  LRDYFEQYGKIEVIEIMTDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKA
  LSKQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRGGFGGSRGGGGYGGS
  GDGYNGFGNDGGYGGGGPGYSGGSRGYGSGGQGYGNQGSGYGGSGSYDSYNNGGGGGFGG
  GSGSNFGGGGSYNDFGNYNNQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGYGGS
  SSSSSYGSGRRF
• Function: Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1. May bind to specific miRNA hairpins ; (Microbial infection) May play a role in HCV RNA replication; (Microbial infection) Cleavage by Enterovirus 71 protease 3C results in increased translation of apoptosis protease activating factor APAF1, leading to apoptosis.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  SARS-CoV-1-host interactions (R-HSA-9692914)
  SARS-CoV-1 modulates host translation machinery (R-HSA-9735869)
  FGFR2 alternative splicing (R-HSA-6803529)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 20	DIS8D4LA	Strong	Autosomal dominant	[1]
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3	DISR6RAR	Strong	Autosomal dominant	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[2]
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	DISK4S94	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) affects the response to substance of Josamycin.	[30]

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 ribonucleoprotein A1 (HNRNPA1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[14]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[15]
Tetracaine	DM9J6C2	Approved	Tetracaine decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[16]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[17]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[18]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[17]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[25]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[26]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[28]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[24]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN affects the localization of Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).	[23]

References

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• [18] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
• [19] Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci. 2011 Mar;120(1):109-22.
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