Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZP02A)

• DOT Name: Coxsackievirus and adenovirus receptor (CXADR)
• Synonyms: CAR; hCAR; CVB3-binding protein; Coxsackievirus B-adenovirus receptor; HCVADR
• Gene Name: CXADR
• Related Disease:
  Dilated cardiomyopathy
  Lymphoma, non-Hodgkin, familial
  Non-hodgkin lymphoma
  Small lymphocytic lymphoma
  Acute lymphocytic leukaemia
  Adult lymphoma
  Arteriosclerosis
  Atherosclerosis
  Bladder cancer
  Carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Craniosynostosis
  Epithelial ovarian cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Immunodeficiency
  leukaemia
  Liver cancer
  Lung carcinoma
  Lymphoid leukemia
  Lymphoma
  Melanoma
  Metabolic disorder
  Metastatic malignant neoplasm
  Neuroblastoma
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Pediatric lymphoma
  Plasma cell myeloma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Brain neoplasm
  Childhood acute lymphoblastic leukemia
  Lung cancer
  Acute myelogenous leukaemia
  B-cell lymphoma
  B-cell neoplasm
  Bone osteosarcoma
  Colorectal carcinoma
  Leukemia
  Matthew-Wood syndrome
  Non-small-cell lung cancer
  Osteosarcoma
  Triple negative breast cancer
  Type-1/2 diabetes
• UniProt ID: CXAR_HUMAN
• PDB ID: 1EAJ; 1F5W; 1JEW; 1KAC; 1P69; 1P6A; 1RSF; 2J12; 2J1K; 2NPL; 2W9L; 2WBW; 3J6L; 3J6M; 3J6N; 3J6O; 7DPZ; 7DQ1; 7VXZ; 7VYK; 7VYL; 7VYM; 7W14
• Pfam ID: PF13927 ; PF07686
• Sequence:
  MALLLCFVLLCGVVDFARSLSITTPEEMIEKAKGETAYLPCKFTLSPEDQGPLDIEWLIS
  PADNQKVDQVIILYSGDKIYDDYYPDLKGRVHFTSNDLKSGDASINVTNLQLSDIGTYQC
  KVKKAPGVANKKIHLVVLVKPSGARCYVDGSEEIGSDFKIKCEPKEGSLPLQYEWQKLSD
  SQKMPTSWLAEMTSSVISVKNASSEYSGTYSCTVRNRVGSDQCLLRLNVVPPSNKAGLIA
  GAIIGTLLALALIGLIIFCCRKKRREEKYEKEVHHDIREDVPPPKSRTSTARSYIGSNHS
  SLGSMSPSNMEGYSKTQYNQVPSEDFERTPQSPTLPPAKVAAPNLSRMGAIPVMIPAQSK
  DGSIV
• Function: Component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. Also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. Upon epithelial CXADR-binding, JAML induces downstream cell signaling events in gamma-delta T-cells through PI3-kinase and MAP kinases. It results in proliferation and production of cytokines and growth factors by T-cells that in turn stimulate epithelial tissues repair; (Microbial infection) Acts as a receptor for adenovirus type C; (Microbial infection) Acts as a receptor for Coxsackievirus B1 to B6.
• Tissue Specificity: Expressed in pancreas, brain, heart, small intestine, testis, prostate and at a lower level in liver and lung. Isoform 5 is ubiquitously expressed. Isoform 3 is expressed in heart, lung and pancreas. In skeletal muscle, isoform 1 is found at the neuromuscular junction and isoform 2 is found in blood vessels. In cardiac muscle, isoform 1 and isoform 2 are found at intercalated disks. In heart expressed in subendothelial layers of the vessel wall but not in the luminal endothelial surface. Expression is elevated in hearts with dilated cardiomyopathy.
• KEGG Pathway:
  Virion - Adenovirus (hsa03267)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Definitive	Altered Expression	[1]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Definitive	Biomarker	[2]
Non-hodgkin lymphoma	DISS2Y8A	Definitive	Biomarker	[2]
Small lymphocytic lymphoma	DIS30POX	Definitive	Biomarker	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[4]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[9]
Craniosynostosis	DIS6J405	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Immunodeficiency	DIS093I0	Strong	Biomarker	[14]
leukaemia	DISS7D1V	Strong	Biomarker	[15]
Liver cancer	DISDE4BI	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[16]
Lymphoid leukemia	DIS65TYQ	Strong	Biomarker	[17]
Lymphoma	DISN6V4S	Strong	Biomarker	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[20]
Obesity	DIS47Y1K	Strong	Biomarker	[21]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Brain neoplasm	DISY3EKS	moderate	Biomarker	[23]
Childhood acute lymphoblastic leukemia	DISJ5D6U	moderate	Biomarker	[4]
Lung cancer	DISCM4YA	moderate	Altered Expression	[16]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[24]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[25]
B-cell neoplasm	DISVY326	Limited	Biomarker	[26]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[27]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[28]
Leukemia	DISNAKFL	Limited	Biomarker	[29]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[30]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[31]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[27]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[32]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[21]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Coxsackievirus and adenovirus receptor (CXADR) affects the response to substance of Mitoxantrone.	[55]

21 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 Coxsackievirus and adenovirus receptor (CXADR).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[41]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[42]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[43]
Valsartan	DMREUQ6	Approved	Valsartan decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[43]
BQ788	DM6KRLW	Phase 3	BQ788 decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[46]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[48]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[49]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[52]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[53]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Coxsackievirus and adenovirus receptor (CXADR).	[54]

3 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 Coxsackievirus and adenovirus receptor (CXADR).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coxsackievirus and adenovirus receptor (CXADR).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Coxsackievirus and adenovirus receptor (CXADR).	[47]

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