Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0HYZIU)

• DOT Name: SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1)
• Gene Name: SH3TC1
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
• UniProt ID: S3TC1_HUMAN
• Pfam ID: PF00018
• Sequence:
  MENLPAVTTEEPTPMGRGPVGPSGGGSTRDQVRTVVMRPSVSWEKAGPEEAKAPVRGDEA
  PPARVAGPAAGTPPCQMGVYPTDLTLQLLAVRRKSRLRDPGLQQTLRGQLRLLENDSREM
  ARVLGELSARLLSIHSDQDRIVVTFKTFEEIWKFSTYHALGFTHHCLANLLMDQAFWLLL
  PSEEEETAIQVHVDENALRLTHESLLIQEGPFFVLCPDHHVRVMTGPRDAGNGPQALRQA
  SGAPQGEAAPETDSSPPSPSVSSEEVAVAAAPEPLIPFHQWALRIPQDPIDDAMGGPVMP
  GNPLMAVGLASALADFQGSGPEEMTFRGGDLIEILGAQVPSLPWCVGRHAASGRVGFVRS
  SLISMQGPVSELESAIFLNEEEKSFFSEGCFSEEDARQLLRRMSGTDVCSVYSLDSVEEA
  ETEQPQEKEIPPPCLSLEPQETLQKVKNVLEQCKTCPGCPQEPASWGLCAASSDVSLQDP
  EEPSFCLEAEDDWEDPEALSSLLLFLNAPGYKASFRGLYDVALPWLSSVFRSFSDEEELT
  GRLAQARGAAKKAGLLMALARLCFLLGRLCSRRLKLSQARVYFEEALGALEGSFGDLFLV
  VAVYANLASIYRKQKNREKCAQVVPKAMALLLGTPDHICSTEAEGELLQLALRRAVGGQS
  LQAEARACFLLARHHVHLKQPEEALPFLERLLLLHRDSGAPEAAWLSDCYLLLADIYSRK
  CLPHLVLSCVKVASLRTRGSLAGSLRSVNLVLQNAPQPHSLPAQTSHYLRQALASLTPGT
  GQALRGPLYTSLAQLYSHHGCHGPAITFMTQAVEASAIAGVRAIVDHLVALAWLHVLHGQ
  SPVALDILQSVRDAVVASEDQEGVIANMVAVALKRTGRTRQAAESYYRALRVARDLGQQR
  NQAVGLANFGALCLHAGASRLAQHYLLEAVRLFSRLPLGECGRDFTHVLLQLGHLCTRQG
  PAQQGKGYYEWALLVAVEMGHVESQLRAVQRLCHFYSAVMPSEAQCVIYHELQLSLACKV
  ADKVLEGQLLETISQLYLSLGTERAYKSALDYTKRSLGIFIDLQKKEKEAHAWLQAGKIY
  YILRQSELVDLYIQVAQNVALYTGDPNLGLELFEAAGDIFFDGAWEREKAVSFYRDRALP
  LAVTTGNRKAELRLCNKLVALLATLEEPQEGLEFAHMALALSITLGDRLNERVAYHRLAA
  LQHRLGHGELAEHFYLKALSLCNSPLEFDEETLYYVKVYLVLGDIIFYDLKDPFDAAGYY
  QLALAAAVDLGNKKAQLKIYTRLATIYHNFLLDREKSLFFYQKARTFATELNVRRVNLPP
  LPLCGWAPWLAPSHPR

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[1]

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 SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[14]

17 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 SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[7]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1).	[15]

References

• [1] Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.