Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQNM3CY)

• DOT Name: T-complex protein 1 subunit eta (CCT7)
• Synonyms: TCP-1-eta; CCT-eta; HIV-1 Nef-interacting protein
• Gene Name: CCT7
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  HIV infectious disease
  Colorectal carcinoma
• UniProt ID: TCPH_HUMAN
• PDB ID: 6NR8 ; 6NR9 ; 6NRA ; 6NRB ; 6NRC ; 6NRD ; 6QB8 ; 7LUM ; 7LUP ; 7NVL ; 7NVM ; 7NVN ; 7NVO ; 7TRG ; 7TTN ; 7TTT ; 7TUB ; 7WU7 ; 7WZ3 ; 7X0A ; 7X0S ; 7X0V ; 7X3J ; 7X3U ; 7X6Q ; 7X7Y ; 8SFE ; 8SFF ; 8SG8 ; 8SG9 ; 8SGC ; 8SGL ; 8SGQ ; 8SH9 ; 8SHA ; 8SHD ; 8SHE ; 8SHF ; 8SHG ; 8SHL ; 8SHN ; 8SHO ; 8SHP ; 8SHQ ; 8SHT
• Pfam ID: PF00118
• Sequence:
  MMPTPVILLKEGTDSSQGIPQLVSNISACQVIAEAVRTTLGPRGMDKLIVDGRGKATISN
  DGATILKLLDVVHPAAKTLVDIAKSQDAEVGDGTTSVTLLAAEFLKQVKPYVEEGLHPQI
  IIRAFRTATQLAVNKIKEIAVTVKKADKVEQRKLLEKCAMTALSSKLISQQKAFFAKMVV
  DAVMMLDDLLQLKMIGIKKVQGGALEDSQLVAGVAFKKTFSYAGFEMQPKKYHNPKIALL
  NVELELKAEKDNAEIRVHTVEDYQAIVDAEWNILYDKLEKIHHSGAKVVLSKLPIGDVAT
  QYFADRDMFCAGRVPEEDLKRTMMACGGSIQTSVNALSADVLGRCQVFEETQIGGERYNF
  FTGCPKAKTCTFILRGGAEQFMEETERSLHDAIMIVRRAIKNDSVVAGGGAIEMELSKYL
  RDYSRTIPGKQQLLIGAYAKALEIIPRQLCDNAGFDATNILNKLRARHAQGGTWYGVDIN
  NEDIADNFEAFVWEPAMVRINALTAASEAACLIVSVDETIKNPRSTVDAPTAAGRGRGRG
  RPH
• Function: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. The TRiC complex plays a role in the folding of actin and tubulin (Probable).
• Reactome Pathway:
  Formation of tubulin folding intermediates by CCT/TriC (R-HSA-389960)
  Folding of actin by CCT/TriC (R-HSA-390450)
  Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[2]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[2]
HIV infectious disease	DISO97HC	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of T-complex protein 1 subunit eta (CCT7).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of T-complex protein 1 subunit eta (CCT7).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of T-complex protein 1 subunit eta (CCT7).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of T-complex protein 1 subunit eta (CCT7).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of T-complex protein 1 subunit eta (CCT7).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of T-complex protein 1 subunit eta (CCT7).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of T-complex protein 1 subunit eta (CCT7).	[9]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of T-complex protein 1 subunit eta (CCT7).	[10]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of T-complex protein 1 subunit eta (CCT7).	[10]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of T-complex protein 1 subunit eta (CCT7).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of T-complex protein 1 subunit eta (CCT7).	[13]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of T-complex protein 1 subunit eta (CCT7).	[15]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of T-complex protein 1 subunit eta (CCT7).	[16]

References

• [1] Extracellular Vesicles from Neurosurgical Aspirates Identifies Chaperonin Containing TCP1 Subunit 6A as a Potential Glioblastoma Biomarker with Prognostic Significance.Proteomics. 2019 Jan;19(1-2):e1800157. doi: 10.1002/pmic.201800157.
• [2] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [3] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [4] Discovery and scoring of protein interaction subnetworks discriminative of late stage human colon cancer.Mol Cell Proteomics. 2009 Apr;8(4):827-45. doi: 10.1074/mcp.M800428-MCP200. Epub 2008 Dec 19.
• [5] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
• [16] Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation. Neurotox Res. 2018 Jan;33(1):123-132. doi: 10.1007/s12640-017-9829-3. Epub 2017 Nov 2.