Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLMD0TK)

• DOT Name: Annexin A7 (ANXA7)
• Synonyms: Annexin VII; Annexin-7; Synexin
• Gene Name: ANXA7
• Related Disease:
  Benign prostatic hyperplasia
  Gastric neoplasm
  Infantile malignant osteopetrosis
  Prostate cancer
  Prostate carcinoma
  Subarachnoid hemorrhage
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Craniosynostosis
  Esophageal cancer
  Fanconi anemia complementation group A
  Gastric adenocarcinoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Her2-receptor negative breast cancer
  leukaemia
  Leukemia
  Myocardial infarction
  Neoplasm
  Neoplasm of esophagus
  Prostate neoplasm
  Stomach cancer
  Adult glioblastoma
  Cardiovascular disease
  Colorectal carcinoma
  Nasopharyngeal carcinoma
  Small lymphocytic lymphoma
  Malaria
  Castration-resistant prostate carcinoma
  Glioblastoma multiforme
  Liver cancer
• UniProt ID: ANXA7_HUMAN
• Pfam ID: PF00191
• Sequence:
  MSYPGYPPTGYPPFPGYPPAGQESSFPPSGQYPYPSGFPPMGGGAYPQVPSSGYPGAGGY
  PAPGGYPAPGGYPGAPQPGGAPSYPGVPPGQGFGVPPGGAGFSGYPQPPSQSYGGGPAQV
  PLPGGFPGGQMPSQYPGGQPTYPSQINTDSFSSYPVFSPVSLDYSSEPATVTQVTQGTIR
  PAANFDAIRDAEILRKAMKGFGTDEQAIVDVVANRSNDQRQKIKAAFKTSYGKDLIKDLK
  SELSGNMEELILALFMPPTYYDAWSLRKAMQGAGTQERVLIEILCTRTNQEIREIVRCYQ
  SEFGRDLEKDIRSDTSGHFERLLVSMCQGNRDENQSINHQMAQEDAQRLYQAGEGRLGTD
  ESCFNMILATRSFPQLRATMEAYSRMANRDLLSSVSREFSGYVESGLKTILQCALNRPAF
  FAERLYYAMKGAGTDDSTLVRIVVTRSEIDLVQIKQMFAQMYQKTLGTMIAGDTSGDYRR
  LLLAIVGQ
• Function: Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis.
• Tissue Specificity: Isoform 1 is expressed in brain, heart and skeletal muscle. Isoform 2 is more abundant in liver, lung, kidney, spleen, fibroblasts and placenta.
• KEGG Pathway: Amyotrophic lateral sclerosis (hsa05014)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Definitive	Biomarker	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Altered Expression	[2]
Infantile malignant osteopetrosis	DIS8C3LZ	Definitive	Altered Expression	[3]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[4]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Biomarker	[5]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[9]
Craniosynostosis	DIS6J405	Strong	Biomarker	[10]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[11]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[17]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[18]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[19]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[18]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[18]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[20]
Malaria	DISQ9Y50	Disputed	Genetic Variation	[21]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Altered Expression	[22]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[18]
Liver cancer	DISDE4BI	Limited	Biomarker	[23]

8 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 Annexin A7 (ANXA7).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Annexin A7 (ANXA7).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Annexin A7 (ANXA7).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Annexin A7 (ANXA7).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Annexin A7 (ANXA7).	[28]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Annexin A7 (ANXA7).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Annexin A7 (ANXA7).	[30]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Annexin A7 (ANXA7).	[31]

References

• [1] ANX7 as a bio-marker in prostate and breast cancer progression.Dis Markers. 2001;17(2):115-20. doi: 10.1155/2001/239602.
• [2] The significance of ANXA7 expression and its correlation with poor cellular differentiation and enhanced metastatic potential of gastric cancer.J Surg Oncol. 2008 Jun 1;97(7):609-14. doi: 10.1002/jso.21046.
• [3] Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis.Proteins. 2014 Dec;82(12):3483-9. doi: 10.1002/prot.24689. Epub 2014 Oct 1.
• [4] SEC-induced activation of ANXA7 GTPase suppresses prostate cancer metastasis.Cancer Lett. 2018 Mar 1;416:11-23. doi: 10.1016/j.canlet.2017.12.008. Epub 2017 Dec 13.
• [5] Annexin A7 induction of neuronal apoptosis via effect on glutamate release in a rat model of subarachnoid hemorrhage.J Neurosurg. 2019 Feb 1;132(3):777-787. doi: 10.3171/2018.9.JNS182003.
• [6] Downregulation of annexin A7 decreases proliferation, migration, and invasion of gastric cancer cells by reducing matrix metalloproteinase 1 and 9 expression.Am J Transl Res. 2019 May 15;11(5):2754-2764. eCollection 2019.
• [7] Annexin A7 is correlated with better clinical outcomes of patients with breast cancer.J Cell Biochem. 2018 Sep;119(9):7577-7584. doi: 10.1002/jcb.27087. Epub 2018 Jun 12.
• [8] Effect of SNX-2112 on proliferation of esophageal cancer cells via regulation of excision repair cross-complementing 1, epidermal growth factor receptor, and p53 expression.Genet Mol Res. 2016 Jun 24;15(2). doi: 10.4238/gmr.15028318.
• [9] Down-regulation of ANXA7 decreases metastatic potential of human hepatocellular carcinoma cells in vitro.Biomed Pharmacother. 2013 May;67(4):285-91. doi: 10.1016/j.biopha.2013.02.005. Epub 2013 Feb 27.
• [10] Copeptin level in the early prediction of cardiorenal syndrome in rats.Exp Ther Med. 2018 Aug;16(2):937-944. doi: 10.3892/etm.2018.6239. Epub 2018 May 30.
• [11] SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein.Biochem Biophys Res Commun. 1999 Nov 30;265(3):630-5. doi: 10.1006/bbrc.1999.1731.
• [12] Annexin A7 expression is downregulated in late-stage gastric cancer and is negatively correlated with the differentiation grade and apoptosis rate.Oncol Lett. 2018 Jun;15(6):9836-9844. doi: 10.3892/ol.2018.8576. Epub 2018 Apr 25.
• [13] Ubiquitin-protein ligase E3C promotes glioma progression by mediating the ubiquitination and degrading of Annexin A7.Sci Rep. 2015 Jun 11;5:11066. doi: 10.1038/srep11066.
• [14] AnnexinA7 down-regulation might suppress the proliferation and metastasis of human hepatocellular carcinoma cells via MAPK/ ERK pathway.Cancer Biomark. 2018;23(4):527-537. doi: 10.3233/CBM-181651.
• [15] ANXA7-GTPase as Tumor Suppressor: Mechanisms and Therapeutic Opportunities.Methods Mol Biol. 2017;1513:23-35. doi: 10.1007/978-1-4939-6539-7_3.
• [16] Transcriptomic and proteomic approach to studying SNX-2112-induced K562 cells apoptosis and anti-leukemia activity in K562-NOD/SCID mice.FEBS Lett. 2009 Jun 18;583(12):1859-66. doi: 10.1016/j.febslet.2009.04.046. Epub 2009 May 8.
• [17] Annexin-A7 protects normal prostate cells and induces distinct patterns of RB-associated cytotoxicity in androgen-sensitive and -resistant prostate cancer cells.Int J Cancer. 2009 Dec 1;125(11):2528-39. doi: 10.1002/ijc.24592.
• [18] Potential role of annexin A7 in cancers.Clin Chim Acta. 2013 Aug 23;423:83-9. doi: 10.1016/j.cca.2013.04.018. Epub 2013 Apr 29.
• [19] The emerging role of sorting nexins in cardiovascular diseases.Clin Sci (Lond). 2019 Mar 15;133(5):723-737. doi: 10.1042/CS20190034. Print 2019 Mar 29.
• [20] The Hsp90 inhibitor SNX-7081 is synergistic with fludarabine nucleoside via DNA damage and repair mechanisms in human, p53-negative chronic lymphocytic leukemia.Oncotarget. 2015 Dec 1;6(38):40981-97. doi: 10.18632/oncotarget.5715.
• [21] Accelerated clearance of Plasmodium-infected erythrocytes in sickle cell trait and annexin-A7 deficiency.Cell Physiol Biochem. 2009;24(5-6):415-28. doi: 10.1159/000257529. Epub 2009 Nov 4.
• [22] High ANXA7 Potentiates Eucalyptol Toxicity in Hormone-refractory Prostate Cancer.Anticancer Res. 2018 Jul;38(7):3831-3842. doi: 10.21873/anticanres.12667.
• [23] Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.PLoS One. 2014 Jul 24;9(7):e102579. doi: 10.1371/journal.pone.0102579. eCollection 2014.
• [24] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [25] 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.
• [26] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [27] 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.
• [28] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [29] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [30] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [31] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.