Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK81F92)

DOT Name Apoptotic chromatin condensation inducer in the nucleus (ACIN1)
Synonyms Acinus
Gene Name ACIN1
Related Disease
Adenoma ( )
Colorectal carcinoma ( )
Immunodeficiency ( )
Neoplasm ( )
Neuroblastoma ( )
Adenocarcinoma ( )
Hepatocellular carcinoma ( )
Lung adenocarcinoma ( )
Minimally invasive lung adenocarcinoma ( )
Intellectual disability ( )
UniProt ID
ACINU_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6G6S
Pfam ID
PF16294 ; PF02037
Sequence
MWRRKHPRTSGGTRGVLSGNRGVEYGSGRGHLGTFEGRWRKLPKMPEAVGTDPSTSRKMA
ELEEVTLDGKPLQALRVTDLKAALEQRGLAKSGQKSALVKRLKGALMLENLQKHSTPHAA
FQPNSQIGEEMSQNSFIKQYLEKQQELLRQRLEREAREAAELEEASAESEDEMIHPEGVA
SLLPPDFQSSLERPELELSRHSPRKSSSISEEKGDSDDEKPRKGERRSSRVRQARAAKLS
EGSQPAEEEEDQETPSRNLRVRADRNLKTEEEEEEEEEEEEDDEEEEGDDEGQKSREAPI
LKEFKEEGEEIPRVKPEEMMDERPKTRSQEQEVLERGGRFTRSQEEARKSHLARQQQEKE
MKTTSPLEEEEREIKSSQGLKEKSKSPSPPRLTEDRKKASLVALPEQTASEEETPPPLLT
KEASSPPPHPQLHSEEEIEPMEGPAPAVLIQLSPPNTDADTRELLVSQHTVQLVGGLSPL
SSPSDTKAESPAEKVPEESVLPLVQKSTLADYSAQKDLEPESDRSAQPLPLKIEELALAK
GITEECLKQPSLEQKEGRRASHTLLPSHRLKQSADSSSSRSSSSSSSSSRSRSRSPDSSG
SRSHSPLRSKQRDVAQARTHANPRGRPKMGSRSTSESRSRSRSRSRSASSNSRKSLSPGV
SRDSSTSYTETKDPSSGQEVATPPVPQLQVCEPKERTSTSSSSVQARRLSQPESAEKHVT
QRLQPERGSPKKCEAEEAEPPAATQPQTSETQTSHLPESERIHHTVEEKEEVTMDTSENR
PENDVPEPPMPIADQVSNDDRPEGSVEDEEKKESSLPKSFKRKISVVSATKGVPAGNSDT
EGGQPGRKRRWGASTATTQKKPSISITTESLKSLIPDIKPLAGQEAVVDLHADDSRISED
ETERNGDDGTHDKGLKICRTVTQVVPAEGQENGQREEEEEEKEPEAEPPVPPQVSVEVAL
PPPAEHEVKKVTLGDTLTRRSISQQKSGVSITIDDPVRTAQVPSPPRGKISNIVHISNLV
RPFTLGQLKELLGRTGTLVEEAFWIDKIKSHCFVTYSTVEEAVATRTALHGVKWPQSNPK
FLCADYAEQDELDYHRGLLVDRPSETKTEEQGIPRPLHPPPPPPVQPPQHPRAEQREQER
AVREQWAEREREMERRERTRSEREWDRDKVREGPRSRSRSRDRRRKERAKSKEKKSEKKE
KAQEEPPAKLLDDLFRKTKAAPCIYWLPLTDSQIVQKEAERAERAKEREKRRKEQEEEEQ
KEREKEAERERNRQLEREKRREHSRERDRERERERERDRGDRDRDRERDRERGRERDRRD
TKRHSRSRSRSTPVRDRGGRR
Function
Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.
Tissue Specificity Ubiquitous. The Ser-1180 phosphorylated form (by SRPK2) is highly expressed and phosphorylated in patients with myeloid hematologic malignancies.
KEGG Pathway
Nucleocytoplasmic transport (hsa03013 )
mR. surveillance pathway (hsa03015 )
Spliceosome (hsa03040 )
Reactome Pathway
mRNA Splicing - Major Pathway (R-HSA-72163 )
Apoptotic cleavage of cellular proteins (R-HSA-111465 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenoma DIS78ZEV Strong Genetic Variation [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [1]
Immunodeficiency DIS093I0 Strong Biomarker [2]
Neoplasm DISZKGEW Strong Genetic Variation [1]
Neuroblastoma DISVZBI4 Strong Biomarker [2]
Adenocarcinoma DIS3IHTY moderate Posttranslational Modification [3]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [4]
Lung adenocarcinoma DISD51WR moderate Posttranslational Modification [3]
Minimally invasive lung adenocarcinoma DIS4W83X moderate Posttranslational Modification [3]
Intellectual disability DISMBNXP Limited Biomarker [5]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [16]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [17]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [19]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [20]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [7]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [9]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [11]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [12]
Selenium DM25CGV Approved Selenium increases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [13]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [14]
Aspirin DM672AH Approved Aspirin decreases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [15]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [12]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Apoptotic chromatin condensation inducer in the nucleus (ACIN1). [18]
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⏷ Show the Full List of 12 Drug(s)

References

1 Effect of once-only flexible sigmoidoscopy screening on the outcomes of subsequent faecal occult blood test screening.J Med Screen. 2019 Mar;26(1):11-18. doi: 10.1177/0969141318785654. Epub 2018 Oct 3.
2 Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-gamma.Br J Cancer. 2006 Jun 19;94(12):1845-52. doi: 10.1038/sj.bjc.6603186. Epub 2006 May 23.
3 The ACIN1 gene is hypermethylated in early stage lung adenocarcinoma.J Thorac Oncol. 2006 Feb;1(2):160-7.
4 An integrated genomic and proteomic approach to identify signatures of endosulfan exposure in hepatocellular carcinoma cells. Pestic Biochem Physiol. 2015 Nov;125:8-16.
5 Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.Hum Mutat. 2015 Dec;36(12):1197-204. doi: 10.1002/humu.22901. Epub 2015 Sep 30.
6 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.
7 Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
8 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.
9 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.
10 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.
11 Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells. J Steroid Biochem Mol Biol. 2003 May;85(1):1-8. doi: 10.1016/s0960-0760(03)00142-0.
12 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
13 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.
14 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
15 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
16 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
17 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.
18 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.
19 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.
20 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.