Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT03UM03)

• DOT Name: TSC22 domain family protein 3 (TSC22D3)
• Synonyms: DSIP-immunoreactive peptide; Protein DIP; hDIP; Delta sleep-inducing peptide immunoreactor; Glucocorticoid-induced leucine zipper protein; GILZ; TSC-22-like protein; TSC-22-related protein; TSC-22R
• Gene Name: TSC22D3
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Autoimmune disease
  Cardiovascular disease
  Depression
  Dermatitis
  Differentiated thyroid carcinoma
  Fibromyalgia
  Gonorrhea
  Inflammatory bowel disease
  leukaemia
  Leukemia
  Lupus
  Myocardial infarction
  Nervous system inflammation
  Obesity
  Osteoporosis
  Plasma cell myeloma
  Post-traumatic stress disorder
  Psoriasis
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Uterine fibroids
  Arthritis
  Asthma
  Colitis
  Epithelial ovarian cancer
  Hyperinsulinemia
  Male infertility
  Melanoma
  Neoplasm
  Primary cutaneous lymphoma
• UniProt ID: T22D3_HUMAN
• Pfam ID: PF01166
• Sequence:
  MNTEMYQTPMEVAVYQLHNFSISFFSSLLGGDVVSVKLDNSASGASVVAIDNKIEQAMDL
  VKNHLMYAVREEVEILKEQIRELVEKNSQLERENTLLKTLASPEQLEKFQSCLSPEEPAP
  ESPQVPEAPGGSAV
• Function: Protects T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3A transcriptional activity that leads to the down-regulation of the pro-apoptotic factor BCL2L11. In macrophages, plays a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10. In T-cells, inhibits anti-CD3-induced NFKB1 nuclear translocation and thereby NFKB1 DNA-binding activities. In vitro, suppresses AP-1 transcription factor complex DNA-binding activities; [Isoform 1]: Inhibits myogenic differentiation and mediates anti-myogenic effects of glucocorticoids by binding and regulating MYOD1 and HDAC1 transcriptional activity resulting in reduced expression of MYOG.
• Tissue Specificity: Ubiquitously expressed, including in the fetal brain and liver . Expressed in brain, lung, spleen and skeletal muscle . Lower levels detected in heart and kidney . Not detected in the pancreas . In non-lymphoid tissues, in the absence of inflammation, the major source of constitutive expression is the macrophage lineage . Also expressed in cells from different hemopoietic cell lineages, including bone marrow cells, CD34+ stem cells, mature B- and T-cells, monocytes and granulocytes . Down-regulated in activated macrophages from inflammatory lesions of delayed-type hypersensitivity (DTH) reactions, such as in tuberculosis and in Crohn disease, whereas in Burkitt lymphoma, persists in macrophages involved in the phagocytosis of apoptotic malignant cells .
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[3]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[4]
Depression	DIS3XJ69	Strong	Altered Expression	[5]
Dermatitis	DISY5SZC	Strong	Biomarker	[6]
Differentiated thyroid carcinoma	DIS1V20Y	Strong	Altered Expression	[7]
Fibromyalgia	DISZJDS2	Strong	Altered Expression	[8]
Gonorrhea	DISQ5AO6	Strong	Altered Expression	[9]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[10]
leukaemia	DISS7D1V	Strong	Biomarker	[11]
Leukemia	DISNAKFL	Strong	Biomarker	[11]
Lupus	DISOKJWA	Strong	Altered Expression	[12]
Myocardial infarction	DIS655KI	Strong	Biomarker	[13]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[10]
Obesity	DIS47Y1K	Strong	Altered Expression	[14]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[16]
Post-traumatic stress disorder	DISHL1EY	Strong	Altered Expression	[17]
Psoriasis	DIS59VMN	Strong	Biomarker	[18]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[19]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[12]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[20]
Arthritis	DIST1YEL	Limited	Altered Expression	[10]
Asthma	DISW9QNS	Limited	Altered Expression	[21]
Colitis	DISAF7DD	Limited	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[22]
Hyperinsulinemia	DISIDWT6	Limited	Biomarker	[23]
Male infertility	DISY3YZZ	Limited	Biomarker	[23]
Melanoma	DIS1RRCY	Limited	Biomarker	[24]
Neoplasm	DISZKGEW	Limited	Altered Expression	[1]
Primary cutaneous lymphoma	DISY0E8H	Limited	Biomarker	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of TSC22 domain family protein 3 (TSC22D3).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TSC22 domain family protein 3 (TSC22D3).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of TSC22 domain family protein 3 (TSC22D3).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of TSC22 domain family protein 3 (TSC22D3).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of TSC22 domain family protein 3 (TSC22D3).	[30]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of TSC22 domain family protein 3 (TSC22D3).	[33]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[34]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[35]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of TSC22 domain family protein 3 (TSC22D3).	[36]
Marinol	DM70IK5	Approved	Marinol increases the expression of TSC22 domain family protein 3 (TSC22D3).	[37]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of TSC22 domain family protein 3 (TSC22D3).	[38]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of TSC22 domain family protein 3 (TSC22D3).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of TSC22 domain family protein 3 (TSC22D3).	[40]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of TSC22 domain family protein 3 (TSC22D3).	[41]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of TSC22 domain family protein 3 (TSC22D3).	[42]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[43]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of TSC22 domain family protein 3 (TSC22D3).	[44]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of TSC22 domain family protein 3 (TSC22D3).	[45]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of TSC22 domain family protein 3 (TSC22D3).	[46]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TSC22 domain family protein 3 (TSC22D3).	[47]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of TSC22 domain family protein 3 (TSC22D3).	[48]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of TSC22 domain family protein 3 (TSC22D3).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of TSC22 domain family protein 3 (TSC22D3).	[50]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[51]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TSC22 domain family protein 3 (TSC22D3).	[53]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of TSC22 domain family protein 3 (TSC22D3).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of TSC22 domain family protein 3 (TSC22D3).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of TSC22 domain family protein 3 (TSC22D3).	[56]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[57]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of TSC22 domain family protein 3 (TSC22D3).	[58]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of TSC22 domain family protein 3 (TSC22D3).	[59]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of TSC22 domain family protein 3 (TSC22D3).	[60]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of TSC22 domain family protein 3 (TSC22D3).	[61]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of TSC22 domain family protein 3 (TSC22D3).	[62]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of TSC22 domain family protein 3 (TSC22D3).	[32]

References

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