Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNPRM8U)

• DOT Name: Heterogeneous nuclear ribonucleoprotein K (HNRNPK)
• Synonyms: hnRNP K; Transformation up-regulated nuclear protein; TUNP
• Gene Name: HNRNPK
• Related Disease:
  Au-Kline syndrome
  Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  B-cell neoplasm
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Clear cell renal carcinoma
  Colon carcinoma
  Glioma
  Head-neck squamous cell carcinoma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Intellectual disability
  Kabuki syndrome
  Liver cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma
  Matthew-Wood syndrome
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Osteoarthritis
  Pituitary tumor
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Triple negative breast cancer
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colorectal carcinoma
  Gastric cancer
  Polydactyly
  Stomach cancer
  Amyotrophic lateral sclerosis
  Nasopharyngeal carcinoma
  Pancreatic cancer
  Type-1 diabetes
• UniProt ID: HNRPK_HUMAN
• PDB ID: 1J5K; 1KHM; 1ZZI; 1ZZJ; 1ZZK; 7CRE; 7CRU; 7RJK; 7RJO
• Pfam ID: PF00013 ; PF08067
• Sequence:
  METEQPEETFPNTETNGEFGKRPAEDMEEEQAFKRSRNTDEMVELRILLQSKNAGAVIGK
  GGKNIKALRTDYNASVSVPDSSGPERILSISADIETIGEILKKIIPTLEEGLQLPSPTAT
  SQLPLESDAVECLNYQHYKGSDFDCELRLLIHQSLAGGIIGVKGAKIKELRENTQTTIKL
  FQECCPHSTDRVVLIGGKPDRVVECIKIILDLISESPIKGRAQPYDPNFYDETYDYGGFT
  MMFDDRRGRPVGFPMRGRGGFDRMPPGRGGRPMPPSRRDYDDMSPRRGPPPPPPGRGGRG
  GSRARNLPLPPPPPPRGGDLMAYDRRGRPGDRYDGMVGFSADETWDSAIDTWSPSEWQMA
  YEPQGGSGYDYSYAGGRGSYGDLGGPIITTQVTIPKDLAGSIIGKGGQRIKQIRHESGAS
  IKIDEPLEGSEDRIITITGTQDQIQNAQYLLQNSVKQYSGKFF
• Function: One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction. As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Viral carcinogenesis (hsa05203)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  HCMV Late Events (R-HSA-9610379)
  SUMOylation of RNA binding proteins (R-HSA-4570464)

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Au-Kline syndrome	DIST62BO	Definitive	Autosomal dominant	[1]
Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome	DISQRIW2	Definitive	Autosomal dominant	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Kabuki syndrome	DISZN97H	Strong	Genetic Variation	[16]
Liver cancer	DISDE4BI	Strong	Altered Expression	[17]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Lymphoma	DISN6V4S	Strong	Altered Expression	[6]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[20]
Melanoma	DIS1RRCY	Strong	Altered Expression	[21]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[25]
Pituitary tumor	DISN67JD	Strong	Biomarker	[26]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[27]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[10]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[28]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[29]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[5]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[31]
Gastric cancer	DISXGOUK	moderate	Biomarker	[32]
Polydactyly	DIS25BMZ	moderate	Genetic Variation	[16]
Stomach cancer	DISKIJSX	moderate	Biomarker	[32]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[33]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[34]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[35]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Heterogeneous nuclear ribonucleoprotein K (HNRNPK) affects the binding of PEITC.	[57]
Sulforaphane	DMQY3L0	Investigative	Heterogeneous nuclear ribonucleoprotein K (HNRNPK) affects the binding of Sulforaphane.	[57]

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 K (HNRNPK).	[37]
Quercetin	DM3NC4M	Approved	Quercetin affects the phosphorylation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[41]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[46]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[49]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[41]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[38]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[42]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[43]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[52]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[54]
9-hydroxyoctadecadienoic acid	DM0FWNJ	Investigative	9-hydroxyoctadecadienoic acid increases the expression of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[56]

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 K (HNRNPK).	[45]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the metabolism of Heterogeneous nuclear ribonucleoprotein K (HNRNPK).	[55]

References

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