Details of Drug Off-Target (DOT)

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

DOT Name	RPA-interacting protein (RPAIN)
Synonyms	hRIP
Gene Name	RPAIN
Related Disease	Hepatocellular carcinoma ( ) Melanoma ( ) Advanced cancer ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Cervical cancer ( ) Cervical carcinoma ( ) Colitis ( ) Diabetic neuropathy ( ) Estrogen-receptor positive breast cancer ( ) Gaucher disease ( ) Glioma ( ) Herpes simplex infection ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Osteosarcoma ( ) Pancreatic cancer ( ) Pancreatic tumour ( ) Prostate cancer ( ) Prostate carcinoma ( ) Small lymphocytic lymphoma ( ) Systemic lupus erythematosus ( ) Type-1/2 diabetes ( ) Ulcerative colitis ( ) Gallbladder cancer ( ) Hypoglycemia ( ) Plasma cell myeloma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Clear cell renal carcinoma ( ) Congenital contractural arachnodactyly ( ) Hyperglycemia ( ) Liver cancer ( ) Nasopharyngeal carcinoma ( ) Neuroendocrine neoplasm ( ) Renal cell carcinoma ( )
UniProt ID	RIP_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF14768 ; PF14767 ; PF14766
Sequence	MAESLRSPRRSLYKLVGSPPWKEAFRQRCLERMRNSRDRLLNRYRQAGSSGPGNSQNSFL VQEVMEEEWNALQSVENCPEDLAQLEELIDMAVLEEIQQELINQEQSIISEYEKSLQFDE KCLSIMLAEWEANPLICPVCTKYNLRITSGVVVCQCGLSIPSHSSELTEQKLRACLEGSI NEHSAHCPHTPEFSVTGGTEEKSSLLMSCLACDTWAVIL
Function	Mediates the import of RPA complex into the nucleus, possibly via some interaction with importin beta. Isoform 2 is sumoylated and mediates the localization of RPA complex into the PML body of the nucleus, thereby participating in RPA function in DNA metabolism.
Tissue Specificity	Widely expressed. Expressed in pancreas, kidney, muscle, liver, lung, placenta, brain, heart, leukocytes, colon, intestine, ovary, testis, prostate, thymus and spleen.

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cervical cancer	DISFSHPF	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[7]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Diabetic neuropathy	DISX6VF8	Strong	Biomarker	[9]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[5]
Gaucher disease	DISTW5JG	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Pancreatic cancer	DISJC981	Strong	Biomarker	[15]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[17]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[19]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[20]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[21]
Gallbladder cancer	DISXJUAF	moderate	Biomarker	[22]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[23]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[24]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[25]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[26]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[27]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[28]
Liver cancer	DISDE4BI	Limited	Biomarker	[25]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[29]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[30]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[26]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

9 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 RPA-interacting protein (RPAIN).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RPA-interacting protein (RPAIN).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RPA-interacting protein (RPAIN).	[33]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RPA-interacting protein (RPAIN).	[34]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of RPA-interacting protein (RPAIN).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of RPA-interacting protein (RPAIN).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of RPA-interacting protein (RPAIN).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RPA-interacting protein (RPAIN).	[35]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of RPA-interacting protein (RPAIN).	[38]
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⏷ Show the Full List of 9 Drug(s)

References

1	Long non-coding RNA SNHG1 functions as a competitive endogenous RNA to regulate PDCD4 expression by sponging miR-195-5p in hepatocellular carcinoma.Gene. 2019 Sep 25;714:143994. doi: 10.1016/j.gene.2019.143994. Epub 2019 Jul 19.
2	Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis.J Cancer Res Clin Oncol. 2018 Mar;144(3):531-542. doi: 10.1007/s00432-018-2582-z. Epub 2018 Jan 19.
3	RIP Kinases in Liver Cell Death, Inflammation and Cancer.Trends Mol Med. 2019 Jan;25(1):47-63. doi: 10.1016/j.molmed.2018.10.007. Epub 2018 Nov 16.
4	Long noncoding RNA NEAT1 regulates the development of osteosarcoma through sponging miR-34a-5p to mediate HOXA13 expression as a competitive endogenous RNA.Mol Genet Genomic Med. 2019 Jun;7(6):e673. doi: 10.1002/mgg3.673. Epub 2019 May 1.
5	The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer.BMC Cancer. 2010 Apr 6;10:126. doi: 10.1186/1471-2407-10-126.
6	Down-regulation of RIP expression by 17-dimethylaminoethylamino-17-demethoxygeldanamycin promotes TRAIL-induced apoptosis in breast tumor cells.Cancer Lett. 2010 Jan 28;287(2):207-15. doi: 10.1016/j.canlet.2009.06.012. Epub 2009 Jul 25.
7	LncRNA STXBP5-AS1 suppressed cervical cancer progression via targeting miR-96-5p/PTEN axis.Biomed Pharmacother. 2019 Sep;117:109082. doi: 10.1016/j.biopha.2019.109082. Epub 2019 Jun 15.
8	Ameliorating effect of TI-1-162, a hydroxyindenone derivative, against TNBS-induced rat colitis is mediated through suppression of RIP/ASK-1/MAPK signaling.Eur J Pharmacol. 2018 May 15;827:94-102. doi: 10.1016/j.ejphar.2018.03.027. Epub 2018 Mar 16.
9	Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.Muscle Nerve. 2010 May;41(5):630-41. doi: 10.1002/mus.21564.
10	Emerging therapeutic targets for Gaucher disease.Expert Opin Ther Targets. 2015 Mar;19(3):321-34. doi: 10.1517/14728222.2014.981530. Epub 2014 Nov 21.
11	Long Non-Coding RNA HOXA-AS2 Enhances The Malignant Biological Behaviors In Glioma By Epigenetically Regulating RND3 Expression.Onco Targets Ther. 2019 Nov 7;12:9407-9419. doi: 10.2147/OTT.S225678. eCollection 2019.
12	Suppression of RIP3-dependent necroptosis by human cytomegalovirus.J Biol Chem. 2015 May 1;290(18):11635-48. doi: 10.1074/jbc.M115.646042. Epub 2015 Mar 16.
13	Parallel Signaling through IRE1 and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival.Cancer Res. 2019 Dec 15;79(24):6190-6203. doi: 10.1158/0008-5472.CAN-19-1116. Epub 2019 Oct 31.
14	Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer.EBioMedicine. 2018 Nov;37:177-187. doi: 10.1016/j.ebiom.2018.10.004. Epub 2018 Oct 9.
15	Effective ablation of pancreatic cancer cells in SCID mice using systemic adenoviral RIP-TK/GCV gene therapy.J Surg Res. 2007 Jul;141(1):45-52. doi: 10.1016/j.jss.2007.02.041. Epub 2007 May 18.
16	Non-invasive MRI tumor imaging and synergistic anticancer effect of HSP90 inhibitor and glycolysis inhibitor in RIP1-Tag2 transgenic pancreatic tumor model.Cancer Chemother Pharmacol. 2008 Nov;62(6):985-94. doi: 10.1007/s00280-008-0688-8. Epub 2008 Feb 6.
17	Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling.Biochem Biophys Res Commun. 2016 Mar 25;472(1):255-61. doi: 10.1016/j.bbrc.2016.02.101. Epub 2016 Feb 26.
18	Mutation analysis of the FAS and TNFR apoptotic cascade genes in hematological malignancies.Exp Hematol. 2001 Feb;29(2):228-33. doi: 10.1016/s0301-472x(00)00623-8.
19	Altered expression of TNF-alpha signaling pathway proteins in systemic lupus erythematosus.J Rheumatol. 2010 Aug 1;37(8):1658-66. doi: 10.3899/jrheum.091123. Epub 2010 Jun 1.
20	Targeting Innate Immunity for Type 1 Diabetes Prevention.Curr Diab Rep. 2017 Sep 27;17(11):113. doi: 10.1007/s11892-017-0930-z.
21	Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice.Toxicol Appl Pharmacol. 2018 Apr 1;344:35-45. doi: 10.1016/j.taap.2018.02.018. Epub 2018 Feb 27.
22	Expression of the RIP-1 gene and its role in growth and invasion of human gallbladder carcinoma.Cell Physiol Biochem. 2014;34(4):1152-65. doi: 10.1159/000366328. Epub 2014 Sep 22.
23	Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide.Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E418-24. doi: 10.1152/ajpendo.00137.2003. Epub 2003 Nov 12.
24	LncRNA MALAT-1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma.J Cell Biochem. 2017 Oct;118(10):3341-3348. doi: 10.1002/jcb.25987. Epub 2017 May 3.
25	Protective effect of RIP and c-FLIP in preventing liver cancer cell apoptosis induced by TRAIL.Int J Clin Exp Pathol. 2015 Jun 1;8(6):6519-25. eCollection 2015.
26	Androgen receptor regulates ASS1P3/miR-34a-5p/ASS1 signaling to promote renal cell carcinoma cell growth.Cell Death Dis. 2019 Apr 18;10(5):339. doi: 10.1038/s41419-019-1330-x.
27	LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells.Cell Cycle. 2019 Apr;18(8):889-897. doi: 10.1080/15384101.2019.1598726. Epub 2019 Apr 14.
28	The diabetogenic, insulin-specific CD8 T cell response primed in the experimental autoimmune diabetes model in RIP-B7.1 mice.Eur J Immunol. 2007 Aug;37(8):2097-103. doi: 10.1002/eji.200737222.
29	Long non-coding RNA LINC01133 mediates nasopharyngeal carcinoma tumorigenesis by binding to YBX1.Am J Cancer Res. 2019 Apr 1;9(4):779-790. eCollection 2019.
30	Amplification of Oncolytic Vaccinia Virus Widespread Tumor Cell Killing by Sunitinib through Multiple Mechanisms.Cancer Res. 2018 Feb 15;78(4):922-937. doi: 10.1158/0008-5472.CAN-15-3308. Epub 2017 Dec 19.
31	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
32	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
33	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
34	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
35	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
36	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
37	Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
38	Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.