Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6USGBK)

• DOT Name: Ankycorbin (RAI14)
• Synonyms: Ankyrin repeat and coiled-coil structure-containing protein; Novel retinal pigment epithelial cell protein; Retinoic acid-induced protein 14
• Gene Name: RAI14
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Breast cancer
  Breast carcinoma
  Neoplasm
  Epithelial ovarian cancer
  Gastric cancer
  Gonorrhea
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
• UniProt ID: RAI14_HUMAN
• Pfam ID: PF12796 ; PF13637
• Sequence:
  MKSLKAKFRKSDTNEWNKNDDRLLQAVENGDAEKVASLLGKKGASATKHDSEGKTAFHLA
  AAKGHVECLRVMITHGVDVTAQDTTGHSALHLAAKNSHHECIRKLLQSKCPAESVDSSGK
  TALHYAAAQGCLQAVQILCEHKSPINLKDLDGNIPLLLAVQNGHSEICHFLLDHGADVNS
  RNKSGRTALMLACEIGSSNAVEALIKKGADLNLVDSLGYNALHYSKLSENAGIQSLLLSK
  ISQDADLKTPTKPKQHDQVSKISSERSGTPKKRKAPPPPISPTQLSDVSSPRSITSTPLS
  GKESVFFAEPPFKAEISSIRENKDRLSDSTTGADSLLDISSEADQQDLLSLLQAKVASLT
  LHNKELQDKLQAKSPKEAEADLSFDSYHSTQTDLGPSLGKPGETSPPDSKSSPSVLIHSL
  GKSTTDNDVRIQQLQEILQDLQKRLESSEAERKQLQVELQSRRAELVCLNNTEISENSSD
  LSQKLKETQSKYEEAMKEVLSVQKQMKLGLVSPESMDNYSHFHELRVTEEEINVLKQDLQ
  NALEESERNKEKVRELEEKLVEREKGTVIKPPVEEYEEMKSSYCSVIENMNKEKAFLFEK
  YQEAQEEIMKLKDTLKSQMTQEASDEAEDMKEAMNRMIDELNKQVSELSQLYKEAQAELE
  DYRKRKSLEDVTAEYIHKAEHEKLMQLTNVSRAKAEDALSEMKSQYSKVLNELTQLKQLV
  DAQKENSVSITEHLQVITTLRTAAKEMEEKISNLKEHLASKEVEVAKLEKQLLEEKAAMT
  DAMVPRSSYEKLQSSLESEVSVLASKLKESVKEKEKVHSEVVQIRSEVSQVKREKENIQT
  LLKSKEQEVNELLQKFQQAQEELAEMKRYAESSSKLEEDKDKKINEMSKEVTKLKEALNS
  LSQLSYSTSSSKRQSQQLEALQQQVKQLQNQLAECKKQHQEVISVYRMHLLYAVQGQMDE
  DVQKVLKQILTMCKNQSQKK
• Function: Plays a role in actin regulation at the ectoplasmic specialization, a type of cell junction specific to testis. Important for establishment of sperm polarity and normal spermatid adhesion. May also promote integrity of Sertoli cell tight junctions at the blood-testis barrier.
• Tissue Specificity: Highly expressed in placenta, muscle, kidney and testis. Moderately expressed in heart, brain, lung, liver and intestine. Isoform 2 is widely expressed and expressed in fetal and adult testes, and spermatozoa.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[3]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[4]
Gonorrhea	DISQ5AO6	Limited	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[3]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Ankycorbin (RAI14) affects the response to substance of Topotecan.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Ankycorbin (RAI14).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankycorbin (RAI14).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankycorbin (RAI14).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankycorbin (RAI14).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ankycorbin (RAI14).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ankycorbin (RAI14).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ankycorbin (RAI14).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ankycorbin (RAI14).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ankycorbin (RAI14).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ankycorbin (RAI14).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ankycorbin (RAI14).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ankycorbin (RAI14).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ankycorbin (RAI14).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Ankycorbin (RAI14).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankycorbin (RAI14).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ankycorbin (RAI14).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankycorbin (RAI14).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankycorbin (RAI14).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ankycorbin (RAI14).	[22]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Ankycorbin (RAI14).	[25]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ankycorbin (RAI14).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ankycorbin (RAI14).	[24]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Ankycorbin (RAI14).	[23]

References

• [1] Retinoic Acid-Induced Protein 14 (RAI14) Promotes mTOR-Mediated Inflammation Under Inflammatory Stress and Chemical Hypoxia in a U87 Glioblastoma Cell Line.Cell Mol Neurobiol. 2019 Mar;39(2):241-254. doi: 10.1007/s10571-018-0644-z. Epub 2018 Dec 15.
• [2] Downregulation of RAI14 inhibits the proliferation and invasion of breast cancer cells.J Cancer. 2019 Oct 18;10(25):6341-6348. doi: 10.7150/jca.34910. eCollection 2019.
• [3] Expression and functional pathway analysis of nuclear receptor NR2F2 in ovarian cancer.J Clin Endocrinol Metab. 2013 Jul;98(7):E1152-62. doi: 10.1210/jc.2013-1081. Epub 2013 May 20.
• [4] High Expression of Retinoic Acid Induced 14 (RAI14) in Gastric Cancer and Its Prognostic Value.Med Sci Monit. 2018 Apr 14;24:2244-2251. doi: 10.12659/msm.910133.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [12] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [17] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [20] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [21] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [22] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [23] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [24] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [25] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [26] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.