Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLQN1E2)

• DOT Name: Heterogeneous nuclear ribonucleoprotein U (HNRNPU)
• Synonyms: hnRNP U; GRIP120; Nuclear p120 ribonucleoprotein; Scaffold-attachment factor A; SAF-A; p120; pp120
• Gene Name: HNRNPU
• Related Disease:
  Adult glioblastoma
  Carcinoma of liver and intrahepatic biliary tract
  Colon cancer
  Colon carcinoma
  Complex neurodevelopmental disorder
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Liver cancer
  West syndrome
  Adenocarcinoma
  Arteriosclerosis
  Atherosclerosis
  Autism spectrum disorder
  Capillary malformation-arteriovenous malformation syndrome
  Developmental and epileptic encephalopathy, 54
  Ductal carcinoma
  Epilepsy
  Hemiplegia
  Infantile epileptic-dyskinetic encephalopathy
  Intellectual disability
  Invasive ductal breast carcinoma
  Isolated congenital microcephaly
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Matthew-Wood syndrome
  Mixed anxiety and depressive disorder
  Mucinous adenocarcinoma
  Neoplasm
  Neurodevelopmental disorder
  Oral cancer
  Oral cavity carcinoma
  Pancreatic cancer
  Preaxial polydactyly of fingers
  Prostate disease
  Schizophrenia
  Squamous cell carcinoma
  Stroke
  Advanced cancer
  Anxiety
  Anxiety disorder
  Epstein barr virus infection
  Glioma
• UniProt ID: HNRPU_HUMAN
• PDB ID: 1ZRJ
• Pfam ID: PF13671 ; PF02037 ; PF00622
• Sequence:
  MSSSPVNVKKLKVSELKEELKKRRLSDKGLKAELMERLQAALDDEEAGGRPAMEPGNGSL
  DLGGDSAGRSGAGLEQEAAAGGDEEEEEEEEEEEGISALDGDQMELGEENGAAGAADSGP
  MEEEEAASEDENGDDQGFQEGEDELGDEEEGAGDENGHGEQQPQPPATQQQQPQQQRGAA
  KEAAGKSSGPTSLFAVTVAPPGARQGQQQAGGKKKAEGGGGGGRPGAPAAGDGKTEQKGG
  DKKRGVKRPREDHGRGYFEYIEENKYSRAKSPQPPVEEEDEHFDDTVVCLDTYNCDLHFK
  ISRDRLSASSLTMESFAFLWAGGRASYGVSKGKVCFEMKVTEKIPVRHLYTKDIDIHEVR
  IGWSLTTSGMLLGEEEFSYGYSLKGIKTCNCETEDYGEKFDENDVITCFANFESDEVELS
  YAKNGQDLGVAFKISKEVLAGRPLFPHVLCHNCAVEFNFGQKEKPYFPIPEEYTFIQNVP
  LEDRVRGPKGPEEKKDCEVVMMIGLPGAGKTTWVTKHAAENPGKYNILGTNTIMDKMMVA
  GFKKQMADTGKLNTLLQRAPQCLGKFIEIAARKKRNFILDQTNVSAAAQRRKMCLFAGFQ
  RKAVVVCPKDEDYKQRTQKKAEVEGKDLPEHAVLKMKGNFTLPEVAECFDEITYVELQKE
  EAQKLLEQYKEESKKALPPEKKQNTGSKKSNKNKSGKNQFNRGGGHRGRGGFNMRGGNFR
  GGAPGNRGGYNRRGNMPQRGGGGGGSGGIGYPYPRAPVFPGRGSYSNRGNYNRGGMPNRG
  NYNQNFRGRGNNRGYKNQSQGYNQWQQGQFWGQKPWSQHYHQGYY
• Function: DNA- and RNA-binding protein involved in several cellular processes such as nuclear chromatin organization, telomere-length regulation, transcription, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing and mitotic cell progression. Plays a role in the regulation of interphase large-scale gene-rich chromatin organization through chromatin-associated RNAs (caRNAs) in a transcription-dependent manner, and thereby maintains genomic stability. Required for the localization of the long non-coding Xist RNA on the inactive chromosome X (Xi) and the subsequent initiation and maintenance of X-linked transcriptional gene silencing during X-inactivation. Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator. Promotes transcription initiation by direct association with the core-TFIIH basal transcription factor complex for the assembly of a functional pre-initiation complex with Pol II in a actin-dependent manner. Blocks Pol II transcription elongation activity by inhibiting the C-terminal domain (CTD) phosphorylation of Pol II and dissociates from Pol II pre-initiation complex prior to productive transcription elongation. Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus. Negatively regulates glucocorticoid-mediated transcriptional activation. Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling. Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression. Participates in the circadian regulation of the core clock component BMAL1 transcription. Plays a role in the regulation of telomere length. Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis. Plays a role in mRNA stability. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Enhances the expression of specific genes, such as tumor necrosis factor TNFA, by regulating mRNA stability, possibly through binding to the 3'-untranslated region (UTR). Plays a role in mitotic cell cycle regulation. Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression. Phosphorylation at Ser-59 by PLK1 is required for chromosome alignement and segregation and progression through mitosis. Contributes also to the targeting of AURKA to mitotic spindle MTs. Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides. Binds to chromatin-associated RNAs (caRNAs). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner. Binds to the Xist RNA. Binds the long non-coding H19 RNA. Binds to SMN1/2 pre-mRNAs at G/U-rich regions. Binds to small nuclear RNAs (snRNAs). Binds to the 3'-UTR of TNFA mRNA. Binds (via RNA-binding RGG-box region) to the long non-coding Xist RNA; this binding is direct and bridges the Xist RNA and the inactive chromosome X (Xi). Also negatively regulates embryonic stem cell differentiation upon LIF signaling. Required for embryonic development. Binds to brown fat long non-coding RNA 1 (Blnc1); facilitates the recruitment of Blnc1 by ZBTB7B required to drive brown and beige fat development and thermogenesis; (Microbial infection) Negatively regulates immunodeficiency virus type 1 (HIV-1) replication by preventing the accumulation of viral mRNA transcripts in the cytoplasm.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[2]
Colon cancer	DISVC52G	Definitive	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Definitive	Altered Expression	[3]
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal dominant	[4]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[2]
Liver cancer	DISDE4BI	Definitive	Biomarker	[2]
West syndrome	DISLIAU9	Definitive	Genetic Variation	[5]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[8]
Capillary malformation-arteriovenous malformation syndrome	DISMN03Q	Strong	Genetic Variation	[9]
Developmental and epileptic encephalopathy, 54	DISBYV7O	Strong	Autosomal dominant	[10]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[11]
Epilepsy	DISBB28L	Strong	Genetic Variation	[5]
Hemiplegia	DISVVH6I	Strong	Genetic Variation	[5]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Genetic Variation	[12]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[13]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[14]
Isolated congenital microcephaly	DISUXHZ6	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[6]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[6]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[15]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[16]
Mixed anxiety and depressive disorder	DISV809X	Strong	Biomarker	[17]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[20]
Oral cancer	DISLD42D	Strong	Biomarker	[21]
Oral cavity carcinoma	DISZXMVL	Strong	Biomarker	[21]
Pancreatic cancer	DISJC981	Strong	Biomarker	[22]
Preaxial polydactyly of fingers	DISXO6C9	Strong	Biomarker	[23]
Prostate disease	DISFVG19	Strong	Altered Expression	[24]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[6]
Stroke	DISX6UHX	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[3]
Anxiety	DISIJDBA	Limited	Biomarker	[26]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[26]
Epstein barr virus infection	DISOO0WT	Limited	Biomarker	[27]
Glioma	DIS5RPEH	Limited	Biomarker	[28]

6 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 ribonucleoprotein U (HNRNPU).	[29]
Arsenic	DMTL2Y1	Approved	Arsenic increases the ubiquitination of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[35]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[43]

16 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 ribonucleoprotein U (HNRNPU).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[32]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[33]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[34]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[36]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[33]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[38]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[39]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[40]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[46]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Dexamethasone affects the localization of Heterogeneous nuclear ribonucleoprotein U (HNRNPU).	[37]

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