Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7MF91K)

• DOT Name: Galectin-9 (LGALS9)
• Synonyms: Gal-9; Ecalectin; Tumor antigen HOM-HD-21
• Gene Name: LGALS9
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Melanoma
  Nephritis
  Pancreatic cancer
  Adult T-cell leukemia/lymphoma
  Alzheimer disease
  Cervical cancer
  Cervical carcinoma
  Chronic hepatitis B virus infection
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cytomegalovirus infection
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatitis
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Multiple sclerosis
  Myelodysplastic syndrome
  Neoplasm
  Pneumococcal meningitis
  Rheumatoid arthritis
  Stomach cancer
  Triple negative breast cancer
  Tuberculosis
  Head-neck squamous cell carcinoma
  HIV infectious disease
  Non-small-cell lung cancer
  Osteoarthritis
  Stroke
  Arthritis
  Asthma
  Dengue
  Liver cancer
  Lupus
  Lymphoma
  Plasma cell myeloma
  Systemic lupus erythematosus
  Systemic sclerosis
• UniProt ID: LEG9_HUMAN
• PDB ID: 2EAK; 2EAL; 2YY1; 2ZHK; 2ZHL; 2ZHM; 2ZHN; 3LSD; 3LSE; 3NV1; 3NV2; 3NV3; 3NV4; 3WLU; 3WV6
• Pfam ID: PF00337
• Sequence:
  MAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGNDIAF
  HFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMVNGILFV
  QYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFPPRPRGRRQK
  PPGVWPANPAPITQTVIHTVQSAPGQMFSTPAIPPMMYPHPAYPMPFITTILGGLYPSKS
  ILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDNSWGSEERSLPRKMPF
  VRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRLEVGGDIQLTHVQT
• Function: Binds galactosides. Has high affinity for the Forssman pentasaccharide. Ligand for HAVCR2/TIM3. Binding to HAVCR2 induces T-helper type 1 lymphocyte (Th1) death. Also stimulates bactericidal activity in infected macrophages by causing macrophage activation and IL1B secretion which restricts intracellular bacterial growth. Ligand for P4HB; the interaction retains P4HB at the cell surface of Th2 T-helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration. Ligand for CD44; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up-regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function. Promotes ability of mesenchymal stromal cells to suppress T-cell proliferation. Expands regulatory T-cells and induces cytotoxic T-cell apoptosis following virus infection. Activates ERK1/2 phosphorylation inducing cytokine (IL-6, IL-8, IL-12) and chemokine (CCL2) production in mast and dendritic cells. Inhibits degranulation and induces apoptosis of mast cells. Induces maturation and migration of dendritic cells. Inhibits natural killer (NK) cell function. Can transform NK cell phenotype from peripheral to decidual during pregnancy. Astrocyte derived galectin-9 enhances microglial TNF production. May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. May provide the molecular basis for urate flux across cell membranes, allowing urate that is formed during purine metabolism to efflux from cells and serving as an electrogenic transporter that plays an important role in renal and gastrointestinal urate excretion. Highly selective to the anion urate; [Isoform 2]: Acts as an eosinophil chemoattractant. It also inhibits angiogenesis. Suppresses IFNG production by natural killer cells.
• Tissue Specificity: Peripheral blood leukocytes and lymphatic tissues. Expressed in lung, liver, breast and kidney with higher levels in tumor endothelial cells than normal endothelium (at protein level) . Expressed in trophoblast cells in decidua and placenta in pregnancy (at protein level) . Isoform 2 is the most abundant isoform expressed in endothelial cells . Upon endothelial cell activation isoform 2 expression decreases while expression of isoform 3 and isoform 5 increases . Isoform 4 decreases in pathological pregnancy .
• Reactome Pathway: Interleukin-2 family signaling (R-HSA-451927)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Breast neoplasm	DISNGJLM	Definitive	Altered Expression	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Nephritis	DISQZQ70	Definitive	Biomarker	[3]
Pancreatic cancer	DISJC981	Definitive	Altered Expression	[4]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[7]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[7]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[15]
Hepatitis	DISXXX35	Strong	Altered Expression	[16]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[17]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[19]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[20]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Pneumococcal meningitis	DISM5U0L	Strong	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[23]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[14]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[26]
HIV infectious disease	DISO97HC	moderate	Biomarker	[27]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[28]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[29]
Stroke	DISX6UHX	moderate	Biomarker	[30]
Arthritis	DIST1YEL	Limited	Biomarker	[31]
Asthma	DISW9QNS	Limited	Biomarker	[32]
Dengue	DISKH221	Limited	Altered Expression	[33]
Liver cancer	DISDE4BI	Limited	Biomarker	[34]
Lupus	DISOKJWA	Limited	Biomarker	[3]
Lymphoma	DISN6V4S	Limited	Biomarker	[35]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[36]
Systemic lupus erythematosus	DISI1SZ7	Limited	Biomarker	[3]
Systemic sclerosis	DISF44L6	Limited	Altered Expression	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Galectin-9 (LGALS9).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Galectin-9 (LGALS9).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Galectin-9 (LGALS9).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Galectin-9 (LGALS9).	[42]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Galectin-9 (LGALS9).	[42]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Galectin-9 (LGALS9).	[43]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Galectin-9 (LGALS9).	[38]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Galectin-9 (LGALS9).	[44]

2 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 Galectin-9 (LGALS9).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Galectin-9 (LGALS9).	[45]

References

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