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
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2D Sequence (FASTA)
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3D Structure (PDB)
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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 REF
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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⏷ Show the Full List of 37 Disease(s)
Molecular Interaction Atlas (MIA) 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.