Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN4GFWD)

• DOT Name: TSC22 domain family protein 1 (TSC22D1)
• Synonyms: Cerebral protein 2; HUCEP-2; Regulatory protein TSC-22; TGFB-stimulated clone 22 homolog; Transforming growth factor beta-1-induced transcript 4 protein
• Gene Name: TSC22D1
• Related Disease:
  Carcinoma
  Diabetic retinopathy
  Salivary gland carcinoma
  Acute myelogenous leukaemia
  Anaplastic astrocytoma
  Astrocytoma
  Brain neoplasm
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Diabetic kidney disease
  HIV infectious disease
  Medulloblastoma
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Advanced cancer
  Prostate cancer
  Prostate carcinoma
  Undifferentiated carcinoma
  Lung cancer
  Lung carcinoma
• UniProt ID: T22D1_HUMAN
• Pfam ID: PF01166
• Sequence:
  MHQPPESTAAAAAAADISARKMAHPAMFPRRGSGSGSASALNAAGTGVGSNATSSEDFPP
  PSLLQPPPPAASSTSGPQPPPPQSLNLLSQAQLQAQPLAPGGTQMKKKSGFQITSVTPAQ
  ISASISSNNSIAEDTESYDDLDESHTEDLSSSEILDVSLSRATDLGEPERSSSEETLNNF
  QEAETPGAVSPNQPHLPQPHLPHLPQQNVVINGNAHPHHLHHHHQIHHGHHLQHGHHHPS
  HVAVASASITGGPPSSPVSRKLSTTGSSDSITPVAPTSAVSSSGSPASVMTNMRAPSTTG
  GIGINSVTGTSTVNNVNITAVGSFNPNVTSSMLGNVNISTSNIPSAAGVSVGPGVTSGVN
  VNILSGMGNGTISSSAAVSSVPNAAAGMTGGSVSSQQQQPTVNTSRFRVVKLDSSSEPFK
  KGRWTCTEFYEKENAVPATEGVLINKVVETVKQNPIEVTSERESTSGSSVSSSVSTLSHY
  TESVGSGEMGAPTVVVQQQQQQQQQQQQQPALQGVTLQQMDFGSTGPQSIPAVSIPQSIS
  QSQISQVQLQSQELSYQQKQGLQPVPLQATMSAATGIQPSPVNVVGVTSALGQQPSISSL
  AQPQLPYSQAAPPVQTPLPGAPPPQQLQYGQQQPMVSTQMAPGHVKSVTQNPASEYVQQQ
  PILQTAMSSGQPSSAGVGAGTTVIPVAQPQGIQLPVQPTAVPAQPAGASVQPVGQAPAAV
  SAVPTGSQIANIGQQANIPTAVQQPSTQVPPSVIQQGAPPSSQVVPPAQTGIIHQGVQTS
  APSLPQQLVIASQSSLLTVPPQPQGVEPVAQGIVSQQLPAVSSLPSASSISVTSQVSSTG
  PSGMPSAPTNLVPPQNIAQTPATQNGNLVQSVSQPPLIATNTNLPLAQQIPLSSTQFSAQ
  SLAQAIGSQIEDARRAAEPSLVGLPQTISGDSGGMSAVSDGSSSSLAASASLFPLKVLPL
  TTPLVDGEDESSSGASVVAIDNKIEQAMDLVKSHLMYAVREEVEVLKEQIKELIEKNSQL
  EQENNLLKTLASPEQLAQFQAQLQTGSPPATTQPQGTTQPPAQPASQGSGPTA
• Function: Transcriptional repressor. Acts on the C-type natriuretic peptide (CNP) promoter. Acts to promote CASP3-mediated apoptosis. Positively regulates TGF-beta signaling by interacting with SMAD7 which inhibits binding of SMAD7 to TGFBR1, preventing recruitment of SMURF ubiquitin ligases to TGFBR1 and inhibiting SMURF-mediated ubiquitination and degradation of TGFBR1. Contributes to enhancement of TGF-beta signaling by binding to and modulating the transcription activator activity of SMAD4. Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TFE3 at E-boxes in the gene proximal promoter. Plays a role in the repression of hematopoietic precursor cell growth. Promotes IL2 deprivation-induced apoptosis in T-lymphocytes, via repression of TSC22D3/GILZ transcription and activation of the caspase cascade ; [Isoform 1]: May act to negatively regulate TGFB3 signaling and thereby inhibit cell death in mammary gland cells; [Isoform 2]: Positively regulates cell death in response to TGFB3 during mammary gland involution.
• Tissue Specificity: Ubiquitously expressed in adult tissues . Expressed in the postmitotic epithelial compartment at the top of intestinal mucosal villi .

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[2]
Salivary gland carcinoma	DISLVGGG	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[4]
Anaplastic astrocytoma	DISSBE0K	Strong	Altered Expression	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cervical cancer	DISFSHPF	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[2]
HIV infectious disease	DISO97HC	Strong	Biomarker	[9]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[8]
Prostate cancer	DISF190Y	Disputed	Altered Expression	[12]
Prostate carcinoma	DISMJPLE	Disputed	Altered Expression	[12]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[1]
Lung cancer	DISCM4YA	Limited	Biomarker	[13]
Lung carcinoma	DISTR26C	Limited	Biomarker	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of TSC22 domain family protein 1 (TSC22D1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of TSC22 domain family protein 1 (TSC22D1).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of TSC22 domain family protein 1 (TSC22D1).	[35]

23 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 TSC22 domain family protein 1 (TSC22D1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of TSC22 domain family protein 1 (TSC22D1).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of TSC22 domain family protein 1 (TSC22D1).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of TSC22 domain family protein 1 (TSC22D1).	[22]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of TSC22 domain family protein 1 (TSC22D1).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[24]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of TSC22 domain family protein 1 (TSC22D1).	[25]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of TSC22 domain family protein 1 (TSC22D1).	[26]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of TSC22 domain family protein 1 (TSC22D1).	[27]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TSC22 domain family protein 1 (TSC22D1).	[28]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of TSC22 domain family protein 1 (TSC22D1).	[29]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[32]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of TSC22 domain family protein 1 (TSC22D1).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TSC22 domain family protein 1 (TSC22D1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of TSC22 domain family protein 1 (TSC22D1).	[24]

References

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