Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR473H8)

DOT Name	Actin filament-associated protein 1 (AFAP1)
Synonyms	110 kDa actin filament-associated protein; AFAP-110
Gene Name	AFAP1
Related Disease	Attenuated familial adenomatous polyposis ( ) Benign prostatic hyperplasia ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma ( ) Cervical cancer ( ) Cervical carcinoma ( ) Cholangiocarcinoma ( ) Congenital contractural arachnodactyly ( ) Endometriosis ( ) Esophageal adenocarcinoma ( ) Esophageal cancer ( ) Familial adenomatous polyposis ( ) Gastric cancer ( ) Lung cancer ( ) Lung carcinoma ( ) Nasopharyngeal carcinoma ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Open-angle glaucoma ( ) Polyp ( ) Prostate cancer ( ) Prostate carcinoma ( ) Stomach cancer ( ) Glaucoma/ocular hypertension ( ) Advanced cancer ( ) Colorectal adenoma ( ) Colorectal carcinoma ( ) Familial adenomatous polyposis 2 ( ) OPTN-related open angle glaucoma ( ) Pancreatic cancer ( ) Polyposis ( )
UniProt ID	AFAP1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00169
Sequence	MEELIVELRLFLELLDHEYLTSTVREKKAVITNILLRIQSSKGFDVKDHAQKQETANSLP APPQMPLPEIPQPWLPPDSGPPPLPTSSLPEGYYEEAVPLSPGKAPEYITSNYDSDAMSS SYESYDEEEEDGKGKKTRHQWPSEEASMDLVKDAKICAFLLRKKRFGQWTKLLCVIKDTK LLCYKSSKDQQPQMELPLQGCNITYIPKDSKKKKHELKITQQGTDPLVLAVQSKEQAEQW LKVIKEAYSGCSGPVDSECPPPPSSPVHKAELEKKLSSERPSSDGEGVVENGITTCNGKE QVKRKKSSKSEAKGTVSKVTGKKITKIISLGKKKPSTDEQTSSAEEDVPTCGYLNVLSNS RWRERWCRVKDNKLIFHKDRTDLKTHIVSIPLRGCEVIPGLDSKHPLTFRLLRNGQEVAV LEASSSEDMGRWIGILLAETGSSTDPEALHYDYIDVEMSASVIQTAKQTFCFMNRRVISA NPYLGGTSNGYAHPSGTALHYDDVPCINGSLKGKKPPVASNGVTGKGKTLSSQPKKADPA AVVKRTGSNAAQYKYGKNRVEADAKRLQTKEEELLKRKEALRNRLAQLRKERKDLRAAIE VNAGRKPQAILEEKLKQLEEECRQKEAERVSLELELTEVKESLKKALAGGVTLGLAIEPK SGTSSPQSPVFRHRTLENSPISSCDTSDTEGPVPVNSAAVLKKSQAAPGSSPCRGHVLRK AKEWELKNGT
Function	Can cross-link actin filaments into both network and bundle structures. May modulate changes in actin filament integrity and induce lamellipodia formation. May function as an adapter molecule that links other proteins, such as SRC and PKC to the actin cytoskeleton. Seems to play a role in the development and progression of prostate adenocarcinoma by regulating cell-matrix adhesions and migration in the cancer cells.
Tissue Specificity	Low expression in normal breast epithelial cell line MCF-10A and in tumorigenic breast cancer cell lines MCF-7, T-47D and ZR-75-1. Highly expressed in the invasive breast cancer cell lines MDA-MB-231 and MDA-MB-435. Overexpressed in prostate carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Attenuated familial adenomatous polyposis	DISGMTLG	Definitive	Genetic Variation	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[6]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[6]
Endometriosis	DISX1AG8	Strong	Biomarker	[7]
Esophageal adenocarcinoma	DISODWFP	Strong	Altered Expression	[8]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[9]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[11]
Lung cancer	DISCM4YA	Strong	Altered Expression	[12]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[12]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[15]
Polyp	DISRSLYF	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[11]
Glaucoma/ocular hypertension	DISLBXBY	moderate	Genetic Variation	[16]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Colorectal adenoma	DISTSVHM	Limited	Genetic Variation	[18]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[19]
Familial adenomatous polyposis 2	DIS62W3Y	Limited	Biomarker	[10]
OPTN-related open angle glaucoma	DISDR98A	Limited	Genetic Variation	[20]
Pancreatic cancer	DISJC981	Limited	Biomarker	[21]
Polyposis	DISZSPOK	Limited	Genetic Variation	[18]
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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 increases the expression of Actin filament-associated protein 1 (AFAP1).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Actin filament-associated protein 1 (AFAP1).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Actin filament-associated protein 1 (AFAP1).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Actin filament-associated protein 1 (AFAP1).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Actin filament-associated protein 1 (AFAP1).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Actin filament-associated protein 1 (AFAP1).	[29]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Actin filament-associated protein 1 (AFAP1).	[30]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Actin filament-associated protein 1 (AFAP1).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Actin filament-associated protein 1 (AFAP1).	[33]
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⏷ Show the Full List of 9 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Actin filament-associated protein 1 (AFAP1).	[27]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Actin filament-associated protein 1 (AFAP1).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Actin filament-associated protein 1 (AFAP1).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Actin filament-associated protein 1 (AFAP1).	[28]
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References

1	Mitochondrial variants in MT-CO2 and D-loop instability are involved in MUTYH-associated polyposis.J Mol Med (Berl). 2015 Nov;93(11):1271-81. doi: 10.1007/s00109-015-1312-0. Epub 2015 Jul 3.
2	AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts.J Clin Invest. 2007 Oct;117(10):2962-73. doi: 10.1172/JCI30710.
3	Expression analysis of AFAP1-AS1 and AFAP1 in breast cancer.Cancer Biomark. 2018;22(1):49-54. doi: 10.3233/CBM-170831.
4	AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB-231 breast cancer cells.J Cell Physiol. 2007 Dec;213(3):740-9. doi: 10.1002/jcp.21143.
5	Upregulation and hypomethylation of lncRNA AFAP1AS1 predicts a poor prognosis and promotes the migration and invasion of cervical cancer.Oncol Rep. 2019 Apr;41(4):2431-2439. doi: 10.3892/or.2019.7027. Epub 2019 Feb 21.
6	LncRNA AFAP1-AS1 promotes growth and metastasis of cholangiocarcinoma cells.Oncotarget. 2017 Apr 6;8(35):58394-58404. doi: 10.18632/oncotarget.16880. eCollection 2017 Aug 29.
7	Long non-coding RNA AFAP1-AS1 promoting epithelial-mesenchymal transition of endometriosis is correlated with transcription factor ZEB1.Am J Reprod Immunol. 2019 Jan;81(1):e13074. doi: 10.1111/aji.13074. Epub 2018 Dec 19.
8	Long noncoding RNA actin filament-associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine-specific demethylase 1 and repressing HMG box-containing protein 1 in non-small-cell lung cancer.Cancer Sci. 2019 Jul;110(7):2211-2225. doi: 10.1111/cas.14039. Epub 2019 May 29.
9	AFAP1-AS1: A novel oncogenic long non-coding RNA in human cancers.Cell Prolif. 2018 Feb;51(1):e12397. doi: 10.1111/cpr.12397. Epub 2017 Oct 22.
10	Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients.Genet Test Mol Biomarkers. 2016 Dec;20(12):777-785. doi: 10.1089/gtmb.2016.0198. Epub 2016 Oct 5.
11	Circulatinglong non-coding RNA FEZF1-AS1 and AFAP1-AS1 serve as potential diagnostic biomarkers for gastric cancer.Pathol Res Pract. 2020 Jan;216(1):152757. doi: 10.1016/j.prp.2019.152757. Epub 2019 Nov 22.
12	Silencing of lncRNA AFAP1-AS1 Inhibits Cell Growth and Metastasis in Clear Cell Renal Cell Carcinoma.Oncol Res. 2019 Jun 21;27(6):653-661. doi: 10.3727/096504018X15420748671075. Epub 2019 Mar 4.
13	Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway.J Exp Clin Cancer Res. 2018 Oct 16;37(1):253. doi: 10.1186/s13046-018-0918-9.
14	LncRNA AFAP1-AS1 Supresses miR-139-5p and Promotes Cell Proliferation and Chemotherapy Resistance of Non-small Cell Lung Cancer by Competitively Upregulating RRM2.Front Oncol. 2019 Oct 22;9:1103. doi: 10.3389/fonc.2019.01103. eCollection 2019.
15	A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nat Commun. 2018 Jun 11;9(1):2278. doi: 10.1038/s41467-018-04555-4.
16	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.Nat Genet. 2018 Sep;50(9):1335-1341. doi: 10.1038/s41588-018-0184-y. Epub 2018 Aug 13.
17	Overexpression of lncRNA AFAP1-AS1 promotes cell proliferation and invasion in gastric cancer.Oncol Lett. 2019 Sep;18(3):3211-3217. doi: 10.3892/ol.2019.10640. Epub 2019 Jul 22.
18	Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients.Int J Cancer. 2006 Apr 15;118(8):1937-40. doi: 10.1002/ijc.21470.
19	Promoter hypermethylation leads to decreased APC mRNA expression in familial polyposis and sporadic colorectal tumours, but does not substitute for truncating mutations.Exp Mol Pathol. 2008 Dec;85(3):201-6. doi: 10.1016/j.yexmp.2008.09.006. Epub 2008 Oct 11.
20	Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.Hum Mol Genet. 2018 Apr 15;27(8):1486-1496. doi: 10.1093/hmg/ddy053.
21	Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice.J Exp Clin Cancer Res. 2019 Feb 28;38(1):107. doi: 10.1186/s13046-019-1051-0.
22	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
23	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.
24	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
25	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
26	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.
27	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
28	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.
29	Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
30	Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
31	Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
32	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.
33	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.