Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZKX4P)

• DOT Name: Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)
• Synonyms: hnRNP A2/B1
• Gene Name: HNRNPA2B1
• Related Disease:
  Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2
  Amyotrophic lateral sclerosis
  Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
• UniProt ID: ROA2_HUMAN
• PDB ID: 1X4B; 5EN1; 5HO4; 5WWE; 5WWF; 5WWG; 6WPQ; 6WQK; 7WM3; 8DU2; 8DUW; 8EC7; 8HNI
• Pfam ID: PF11627 ; PF00076
• Sequence:
  MEKTLETVPLERKKREKEQFRKLFIGGLSFETTEESLRNYYEQWGKLTDCVVMRDPASKR
  SRGFGFVTFSSMAEVDAAMAARPHSIDGRVVEPKRAVAREESGKPGAHVTVKKLFVGGIK
  EDTEEHHLRDYFEEYGKIDTIEIITDRQSGKKRGFGFVTFDDHDPVDKIVLQKYHTINGH
  NAEVRKALSRQEMQEVQSSRSGRGGNFGFGDSRGGGGNFGPGPGSNFRGGSDGYGSGRGF
  GDGYNGYGGGPGGGNFGGSPGYGGGRGGYGGGGPGYGNQGGGYGGGYDNYGGGNYGSGNY
  NDFGNYNQQPSNYGPMKSGNFGGSRNMGGPYGGGNYGPGGSGGSGGYGGRSRY
• Function: Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs. Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm. Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion. Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts. Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs. Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs. 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. Also plays a role in the activation of the innate immune response. Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6. In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production ; (Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport.
• KEGG Pathway: Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2	DIS3ZXZQ	Strong	Autosomal dominant	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Moderate	Autosomal dominant	[2]
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	DISK4S94	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[26]

28 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[10]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[16]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[17]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[6]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[18]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[22]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[29]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).	[30]

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 ribonucleoproteins A2/B1 (HNRNPA2B1).	[20]

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