Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE0OVK5)

• DOT Name: SAP domain-containing ribonucleoprotein (SARNP)
• Synonyms: Cytokine-induced protein of 29 kDa; Nuclear protein Hcc-1; Proliferation-associated cytokine-inducible protein CIP29
• Gene Name: SARNP
• Related Disease:
  Carcinoma of esophagus
  Delirium
  Esophageal cancer
  Hepatitis C virus infection
  Neoplasm of esophagus
  Schizophrenia
  Advanced cancer
  Cholangiocarcinoma
  Chronic kidney disease
  Chronic renal failure
  End-stage renal disease
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Pancreatic adenocarcinoma
  Breast cancer
  Breast carcinoma
  Neoplasm
  Primary sclerosing cholangitis
  Sclerosing cholangitis
  Triple negative breast cancer
• UniProt ID: SARNP_HUMAN
• PDB ID: 2DO1
• Pfam ID: PF02037
• Sequence:
  MATETVELHKLKLAELKQECLARGLETKGIKQDLIHRLQAYLEEHAEEEANEEDVLGDET
  EEEETKPIELPVKEEEPPEKTVDVAAEKKVVKITSEIPQTERMQKRAERFNVPVSLESKK
  AARAARFGISSVPTKGLSSDNKPMVNLDKLKERAQRFGLNVSSISRKSEDDEKLKKRKER
  FGIVTSSAGTGTTEDTEAKKRKRAERFGIA
• Function: Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.
• Tissue Specificity: Low expression in spleen, liver, pancreas, testis, thymus, heart, and kidney. Increased levels are seen in hepatocellular carcinoma and pancreatic adenocarcinoma.
• Reactome Pathway:
  mRNA 3'-end processing (R-HSA-72187)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Definitive	Biomarker	[1]
Delirium	DIS2OKP1	Definitive	Genetic Variation	[2]
Esophageal cancer	DISGB2VN	Definitive	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Definitive	Biomarker	[3]
Neoplasm of esophagus	DISOLKAQ	Definitive	Biomarker	[1]
Schizophrenia	DISSRV2N	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[5]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[6]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[6]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[6]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Altered Expression	[10]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[11]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[11]
Neoplasm	DISZKGEW	Limited	Biomarker	[12]
Primary sclerosing cholangitis	DISTH5WJ	Limited	Biomarker	[13]
Sclerosing cholangitis	DIS7GZNB	Limited	Biomarker	[13]
Triple negative breast cancer	DISAMG6N	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	SAP domain-containing ribonucleoprotein (SARNP) decreases the response to substance of Doxorubicin.	[24]

2 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 SAP domain-containing ribonucleoprotein (SARNP).	[14]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of SAP domain-containing ribonucleoprotein (SARNP).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SAP domain-containing ribonucleoprotein (SARNP).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of SAP domain-containing ribonucleoprotein (SARNP).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SAP domain-containing ribonucleoprotein (SARNP).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SAP domain-containing ribonucleoprotein (SARNP).	[18]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SAP domain-containing ribonucleoprotein (SARNP).	[19]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of SAP domain-containing ribonucleoprotein (SARNP).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SAP domain-containing ribonucleoprotein (SARNP).	[22]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of SAP domain-containing ribonucleoprotein (SARNP).	[23]

References

• [1] No association of single nucleotide polymorphisms involved in GHRL and GHSR with cancer risk: a meta-analysis.Cancer Biomark. 2015;15(1):89-97. doi: 10.3233/CBM-140441.
• [2] Short tandem repeat (STR) replacements in UTRs and introns suggest an important role for certain STRs in gene expression and disease.Gene. 2005 Jan 3;344:203-11. doi: 10.1016/j.gene.2004.09.034. Epub 2004 Dec 7.
• [3] The long-term outcomes of hepatitis C virus core antigen-positive Japanese renal allograft recipients.Clin Exp Nephrol. 2017 Dec;21(6):1113-1123. doi: 10.1007/s10157-017-1394-9. Epub 2017 Mar 29.
• [4] Overexpression of HCC1/CAPER may play a role in lung cancer carcinogenesis.Tumour Biol. 2014 Jul;35(7):6311-7. doi: 10.1007/s13277-014-1819-y. Epub 2014 Mar 19.
• [5] Temporary Balloon Occlusion for Hepatic Arterial Flow Redistribution during Yttrium-90 Radioembolization.J Vasc Interv Radiol. 2019 Aug;30(8):1201-1206. doi: 10.1016/j.jvir.2019.01.003. Epub 2019 May 30.
• [6] HCC-1, a novel chemokine from human plasma.J Exp Med. 1996 Jan 1;183(1):295-9. doi: 10.1084/jem.183.1.295.
• [7] Hepatitis C virus core protein fused to hepatitis B virus core antigen for serological diagnosis of both hepatitis C and hepatitis B infections by ELISA.J Med Virol. 1999 Feb;57(2):104-10.
• [8] A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX.Oncogenesis. 2018 Feb 23;7(2):22. doi: 10.1038/s41389-017-0010-x.
• [9] Evaluation of serum autoantibodies against tumor-associated antigens as biomarkers in lung cancer.Tumour Biol. 2017 Oct;39(10):1010428317711662. doi: 10.1177/1010428317711662.
• [10] An integrated approach in the discovery and characterization of a novel nuclear protein over-expressed in liver and pancreatic tumors.FEBS Lett. 2001 May 11;496(2-3):109-16. doi: 10.1016/s0014-5793(01)02409-7.
• [11] SARNP, a participant in mRNA splicing and export, negatively regulates E-cadherin expression via interaction with pinin.J Cell Physiol. 2020 Feb;235(2):1543-1555. doi: 10.1002/jcp.29073. Epub 2019 Jul 17.
• [12] An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 1. Flt3 ligand gene transfer increases antitumor effects of a radio-inducible suicide gene therapy in an ectopic tumor model.Radiat Res. 2014 Aug;182(2):191-200. doi: 10.1667/RR13594.1. Epub 2014 Jun 27.
• [13] The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients.Medicine (Baltimore). 2003 Nov;82(6):373-84. doi: 10.1097/01.md.0000100046.06009.b0.
• [14] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: proteomic characterization. Exp Cell Res. 2007 Jan 15;313(2):357-68. doi: 10.1016/j.yexcr.2006.10.016. Epub 2006 Oct 25.
• [17] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [18] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [19] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [20] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [21] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [22] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [23] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [24] Nuclear proteomics with XRCC3 knockdown to reveal the development of doxorubicin-resistant uterine cancer. Toxicol Sci. 2014 Jun;139(2):396-406. doi: 10.1093/toxsci/kfu051. Epub 2014 Mar 27.