Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM33P73)

• DOT Name: Annexin A13 (ANXA13)
• Synonyms: Annexin XIII; Annexin-13; Intestine-specific annexin; ISA
• Gene Name: ANXA13
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  facioscapulohumeral muscular dystrophy
  Frontometaphyseal dysplasia 1
  Hepatitis B virus infection
  Influenza
  Neoplasm
  Encephalitis
  Castration-resistant prostate carcinoma
  Type-1 diabetes
• UniProt ID: ANX13_HUMAN
• PDB ID: 6B3I
• Pfam ID: PF00191
• Sequence:
  MGNRHAKASSPQGFDVDRDAKKLNKACKGMGTNEAAIIEILSGRTSDERQQIKQKYKATY
  GKELEEVLKSELSGNFEKTALALLDRPSEYAARQLQKAMKGLGTDESVLIEVLCTRTNKE
  IIAIKEAYQRLFDRSLESDVKGDTSGNLKKILVSLLQANRNEGDDVDKDLAGQDAKDLYD
  AGEGRWGTDELAFNEVLAKRSYKQLRATFQAYQILIGKDIEEAIEEETSGDLQKAYLTLV
  RCAQDCEDYFAERLYKSMKGAGTDEETLIRIVVTRAEVDLQGIKAKFQEKYQKSLSDMVR
  SDTSGDFRKLLVALLH
• Function: [Isoform A]: Binds to membranes enriched in phosphatidylserine or phosphatidylglycerol in a calcium-dependent manner. Half-maximal membrane binding requires about 60 uM calcium. Does not bind to membranes that lack phospholipids with an acidic headgroup ; [Isoform B]: Binds to membranes enriched in phosphatidylserine or phosphatidylglycerol in a calcium-dependent manner, but requires higher calcium levels for membrane binding than isoform A. Half-maximal membrane binding requires about 320 uM calcium.
• Tissue Specificity: Detected in epithelial cells in colon and jejunum (at protein level). Detected in epithelial cells in jejunum.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Biomarker	[5]
Frontometaphyseal dysplasia 1	DIS2MB3L	Strong	Biomarker	[5]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[6]
Influenza	DIS3PNU3	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Encephalitis	DISLD1RL	moderate	Biomarker	[9]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Genetic Variation	[10]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Annexin A13 (ANXA13).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Annexin A13 (ANXA13).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Annexin A13 (ANXA13).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Annexin A13 (ANXA13).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Annexin A13 (ANXA13).	[15]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Annexin A13 (ANXA13).	[16]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Annexin A13 (ANXA13).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Annexin A13 (ANXA13).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Annexin A13 (ANXA13).	[19]

References

• [1] Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.J Immunother. 2014 Feb-Mar;37(2):84-92. doi: 10.1097/CJI.0000000000000017.
• [2] Analysis of breast cancer subtypes by AP-ISA biclustering.BMC Bioinformatics. 2017 Nov 14;18(1):481. doi: 10.1186/s12859-017-1926-z.
• [3] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [4] Annexin A13 promotes tumor cell invasion in vitro and is associated with metastasis in human colorectal cancer.Oncotarget. 2017 Mar 28;8(13):21663-21673. doi: 10.18632/oncotarget.15523.
• [5] Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant.Vaccines (Basel). 2019 Oct 9;7(4):143. doi: 10.3390/vaccines7040143.
• [6] Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720.Vaccine. 2005 Jan 4;23(7):857-64. doi: 10.1016/j.vaccine.2004.08.020.
• [7] Comparative assessment of humoral immune responses of aluminum hydroxide and oil-emulsion adjuvants in Influenza (H9N2) and Newcastle inactive vaccines to chickens.Artif Cells Nanomed Biotechnol. 2017 Feb;45(1):84-89. doi: 10.3109/21691401.2015.1129626. Epub 2016 Jan 13.
• [8] The role of PIP5K1/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1 inhibitor.Oncogene. 2019 Jan;38(3):375-389. doi: 10.1038/s41388-018-0438-2. Epub 2018 Aug 13.
• [9] Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.PLoS One. 2016 Aug 22;11(8):e0159564. doi: 10.1371/journal.pone.0159564. eCollection 2016.
• [10] Safety and Immunogenicity of a Human Epidermal Growth Factor Receptor 1 (HER1)-Based Vaccine in Prostate Castration-Resistant Carcinoma Patients: A Dose-Escalation Phase I Study Trial.Front Pharmacol. 2017 May 10;8:263. doi: 10.3389/fphar.2017.00263. eCollection 2017.
• [11] ISA-2011B, a Phosphatidylinositol 4-Phosphate 5-Kinase Inhibitor, Impairs CD28-Dependent Costimulatory and Pro-inflammatory Signals in Human T Lymphocytes.Front Immunol. 2017 Apr 26;8:502. doi: 10.3389/fimmu.2017.00502. eCollection 2017.
• [12] 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.
• [13] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [14] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Br J Nutr. 2008 Apr;99(4):703-8.
• [17] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [18] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [19] 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.