Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJBI0VN)

• DOT Name: Actin filament-associated protein 1-like 2 (AFAP1L2)
• Synonyms: AFAP1-like protein 2
• Gene Name: AFAP1L2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Colorectal carcinoma
  Ductal carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Invasive breast carcinoma
  Neoplasm
  Skin neoplasm
  Squamous cell carcinoma
  Stomach cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Chronic obstructive pulmonary disease
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Melanoma
  Thyroid gland papillary carcinoma
• UniProt ID: AF1L2_HUMAN
• PDB ID: 2COF
• Pfam ID: PF00169
• Sequence:
  MERYKALEQLLTELDDFLKILDQENLSSTALVKKSCLAELLRLYTKSSSSDEEYIYMNKV
  TINKQQNAESQGKAPEEQGLLPNGEPSQHSSAPQKSLPDLPPPKMIPERKQLAIPKTESP
  EGYYEEAEPYDTSLNEDGEAVSSSYESYDEEDGSKGKSAPYQWPSPEAGIELMRDARICA
  FLWRKKWLGQWAKQLCVIKDNRLLCYKSSKDHSPQLDVNLLGSSVIHKEKQVRKKEHKLK
  ITPMNADVIVLGLQSKDQAEQWLRVIQEVSGLPSEGASEGNQYTPDAQRFNCQKPDIAEK
  YLSASEYGSSVDGHPEVPETKDVKKKCSAGLKLSNLMNLGRKKSTSLEPVERSLETSSYL
  NVLVNSQWKSRWCSVRDNHLHFYQDRNRSKVAQQPLSLVGCEVVPDPSPDHLYSFRILHK
  GEELAKLEAKSSEEMGHWLGLLLSESGSKTDPEEFTYDYVDADRVSCIVSAAKNSLLLMQ
  RKFSEPNTYIDGLPSQDRQEELYDDVDLSELTAAVEPTEEATPVADDPNERESDRVYLDL
  TPVKSFLHGPSSAQAQASSPTLSCLDNATEALPADSGPGPTPDEPCIKCPENLGEQQLES
  LEPEDPSLRITTVKIQTEQQRISFPPSCPDAVVATPPGASPPVKDRLRVTSAEIKLGKNR
  TEAEVKRYTEEKERLEKKKEEIRGHLAQLRKEKRELKETLLKCTDKEVLASLEQKLKEID
  EECRGEESRRVDLELSIMEVKDNLKKAEAGPVTLGTTVDTTHLENVSPRPKAVTPASAPD
  CTPVNSATTLKNRPLSVVVTGKGTVLQKAKEWEKKGAS
• Function: May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation.
• Tissue Specificity: Detected in spleen and thyroid, and at lower levels in kidney, brain, lung and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Ductal carcinoma	DIS15EA5	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Invasive breast carcinoma	DISANYTW	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Skin neoplasm	DIS16DDV	Strong	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[10]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[6]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[11]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[7]
Liver cancer	DISDE4BI	Limited	Altered Expression	[7]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[12]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[13]

12 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-like 2 (AFAP1L2).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[18]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[20]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Actin filament-associated protein 1-like 2 (AFAP1L2).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Actin filament-associated protein 1-like 2 (AFAP1L2).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Actin filament-associated protein 1-like 2 (AFAP1L2).	[23]

References

• [1] Knockdown of XB130 restrains cancer stem cell-like phenotype through inhibition of Wnt/-Catenin signaling in breast cancer.Mol Carcinog. 2019 Oct;58(10):1832-1845. doi: 10.1002/mc.23071. Epub 2019 Jun 20.
• [2] XB130 is overexpressed in prostate cancer and involved in cell growth and invasion.Oncotarget. 2016 Sep 13;7(37):59377-59387. doi: 10.18632/oncotarget.11074.
• [3] XB130 enhances invasion and migration of human colorectal cancer cells by promoting epithelialmesenchymal transition.Mol Med Rep. 2017 Oct;16(4):5592-5598. doi: 10.3892/mmr.2017.7279. Epub 2017 Aug 18.
• [4] Expression of XB130 in human ductal breast cancer.Int J Clin Exp Pathol. 2015 May 1;8(5):5300-8. eCollection 2015.
• [5] XB130 as an independent prognostic factor in human esophageal squamous cell carcinoma.Ann Surg Oncol. 2013 Sep;20(9):3140-50. doi: 10.1245/s10434-012-2474-4. Epub 2012 Jul 18.
• [6] Silencing of XB130 is associated with both the prognosis and chemosensitivity of gastric cancer.PLoS One. 2012;7(8):e41660. doi: 10.1371/journal.pone.0041660. Epub 2012 Aug 23.
• [7] XB130 Knockdown Inhibits the Proliferation, Invasiveness, and Metastasis of Hepatocellular Carcinoma Cells and Sensitizes them to TRAIL-Induced Apoptosis.Chin Med J (Engl). 2018 Oct 5;131(19):2320-2331. doi: 10.4103/0366-6999.241800.
• [8] XB130 deficiency enhances carcinogen-induced skin tumorigenesis.Carcinogenesis. 2019 Nov 25;40(11):1363-1375. doi: 10.1093/carcin/bgz042.
• [9] Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.Carcinogenesis. 2018 Mar 8;39(3):336-346. doi: 10.1093/carcin/bgx113.
• [10] XB130, a novel adaptor protein, promotes thyroid tumor growth.Am J Pathol. 2011 Jan;178(1):391-401. doi: 10.1016/j.ajpath.2010.11.024. Epub 2010 Dec 23.
• [11] XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells.Oncotarget. 2015 Jul 20;6(20):18050-65. doi: 10.18632/oncotarget.3777.
• [12] Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk.Int J Cancer. 2015 Oct 15;137(8):1901-1909. doi: 10.1002/ijc.29570. Epub 2015 May 26.
• [13] XB130, a tissue-specific adaptor protein that couples the RET/PTC oncogenic kinase to PI 3-kinase pathway.Oncogene. 2009 Feb 19;28(7):937-49. doi: 10.1038/onc.2008.447. Epub 2008 Dec 8.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [16] 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.
• [17] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [18] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [19] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [20] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [21] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [22] 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.
• [23] 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.
• [24] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.