Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMG16BZ)

• DOT Name: Lymphocyte antigen 6E (LY6E)
• Synonyms: Ly-6E; Retinoic acid-induced gene E protein; RIG-E; Stem cell antigen 2; SCA-2; Thymic shared antigen 1; TSA-1
• Gene Name: LY6E
• Related Disease:
  Adult respiratory distress syndrome
  Advanced cancer
  Autosomal dominant cerebellar ataxia type II
  Breast cancer
  Breast carcinoma
  Chagas disease
  Colonic neoplasm
  Creutzfeldt Jacob disease
  Deafness
  Dementia
  Depression
  Dystonia
  Essential tremor
  Familial amyotrophic lateral sclerosis
  Hepatocellular carcinoma
  Hereditary spastic paraplegia
  Huntington disease
  Immunodeficiency
  Influenza
  Late-onset Parkinson disease
  Lupus
  Lupus nephritis
  Motor neurone disease
  Neoplasm
  Pancreatic tumour
  Parkinsonian disorder
  Pathologic nystagmus
  Prostate cancer
  Prostate carcinoma
  Sleep disorder
  Spinocerebellar ataxia type 2
  Spinocerebellar ataxia type 3
  Spinocerebellar ataxia type 6
  Systemic lupus erythematosus
  Wiskott-Aldrich syndrome
  Hereditary ataxia
  Multiple sclerosis
  Amyotrophic lateral sclerosis
  Dentatorubral-pallidoluysian atrophy
  Gastric cancer
  Kennedy disease
  Post-traumatic stress disorder
  Spinocerebellar ataxia
  Spinocerebellar ataxia type 1
  Stomach cancer
• UniProt ID: LY6E_HUMAN
• Pfam ID: PF00021
• Sequence:
  MKIFLPVLLAALLGVERASSLMCFSCLNQKSNLYCLKPTICSDQDNYCVTVSASAGIGNL
  VTFGHSLSKTCSPACPIPEGVNVGVASMGISCCQSFLCNFSAADGGLRASVTLLGAGLLL
  SLLPALLRFGP
• Function: GPI-anchored cell surface protein that regulates T-lymphocytes proliferation, differentiation, and activation. Regulates the T-cell receptor (TCR) signaling by interacting with component CD3Z/CD247 at the plasma membrane, leading to CD3Z/CD247 phosphorylation modulation. Restricts the entry of human coronaviruses, including SARS-CoV, MERS-CoV and SARS-CoV-2, by interfering with spike protein-mediated membrane fusion. Also plays an essential role in placenta formation by acting as the main receptor for syncytin-A (SynA). Therefore, participates in the normal fusion of syncytiotrophoblast layer I (SynT-I) and in the proper morphogenesis of both fetal and maternal vasculatures within the placenta. May also act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity; (Microbial infection) Promotes entry, likely through an enhanced virus-cell fusion process, of various viruses including HIV-1, West Nile virus, dengue virus and Zika virus. In contrast, the paramyxovirus PIV5, which enters at the plasma membrane, does not require LY6E. Mechanistically, adopts a microtubule-like organization upon viral infection and enhances viral uncoating after endosomal escape.
• Tissue Specificity: Widely expressed, predominantly in liver, kidney, ovary, spleen and peripheral blood Leukocytes.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Chagas disease	DIS8KNVF	Strong	Biomarker	[5]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[6]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[7]
Deafness	DISKCLH4	Strong	Genetic Variation	[8]
Dementia	DISXL1WY	Strong	Genetic Variation	[9]
Depression	DIS3XJ69	Strong	Genetic Variation	[10]
Dystonia	DISJLFGW	Strong	Genetic Variation	[11]
Essential tremor	DIS7GBKQ	Strong	Biomarker	[12]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
Hereditary spastic paraplegia	DISGZQV1	Strong	Genetic Variation	[15]
Huntington disease	DISQPLA4	Strong	Biomarker	[16]
Immunodeficiency	DIS093I0	Strong	Biomarker	[2]
Influenza	DIS3PNU3	Strong	Biomarker	[17]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[18]
Lupus	DISOKJWA	Strong	Biomarker	[19]
Lupus nephritis	DISCVGPZ	Strong	Biomarker	[20]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Altered Expression	[22]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[23]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[10]
Pathologic nystagmus	DIS1QSPO	Strong	Biomarker	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[26]
Spinocerebellar ataxia type 2	DISF7WDI	Strong	Biomarker	[27]
Spinocerebellar ataxia type 3	DISQBQID	Strong	Genetic Variation	[10]
Spinocerebellar ataxia type 6	DISH7224	Strong	Genetic Variation	[28]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[29]
Wiskott-Aldrich syndrome	DISATMDB	Strong	Biomarker	[30]
Hereditary ataxia	DIS6JNI3	moderate	Biomarker	[31]
Multiple sclerosis	DISB2WZI	Disputed	Genetic Variation	[32]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[33]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Limited	Genetic Variation	[34]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[22]
Kennedy disease	DISXZVM1	Limited	Genetic Variation	[35]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[36]
Spinocerebellar ataxia	DISYMHUK	Limited	Genetic Variation	[34]
Spinocerebellar ataxia type 1	DISF7BO2	Limited	Biomarker	[37]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Lymphocyte antigen 6E (LY6E) affects the response to substance of Etoposide.	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lymphocyte antigen 6E (LY6E).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lymphocyte antigen 6E (LY6E).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lymphocyte antigen 6E (LY6E).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Lymphocyte antigen 6E (LY6E).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lymphocyte antigen 6E (LY6E).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lymphocyte antigen 6E (LY6E).	[43]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Lymphocyte antigen 6E (LY6E).	[44]
Selenium	DM25CGV	Approved	Selenium increases the expression of Lymphocyte antigen 6E (LY6E).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Lymphocyte antigen 6E (LY6E).	[46]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Lymphocyte antigen 6E (LY6E).	[47]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Lymphocyte antigen 6E (LY6E).	[44]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Lymphocyte antigen 6E (LY6E).	[44]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Lymphocyte antigen 6E (LY6E).	[44]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Lymphocyte antigen 6E (LY6E).	[44]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Lymphocyte antigen 6E (LY6E).	[44]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Lymphocyte antigen 6E (LY6E).	[39]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Lymphocyte antigen 6E (LY6E).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lymphocyte antigen 6E (LY6E).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Lymphocyte antigen 6E (LY6E).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lymphocyte antigen 6E (LY6E).	[51]

1 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 affects the methylation of Lymphocyte antigen 6E (LY6E).	[48]

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