Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA7GQN9)

• DOT Name: T-complex protein 1 subunit theta (CCT8)
• Synonyms: TCP-1-theta; CCT-theta; Chaperonin containing T-complex polypeptide 1 subunit 8; Renal carcinoma antigen NY-REN-15
• Gene Name: CCT8
• Related Disease:
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Pancreatic cancer
• UniProt ID: TCPQ_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:
  MALHVPKAPGFAQMLKEGAKHFSGLEEAVYRNIQACKELAQTTRTAYGPNGMNKMVINHL
  EKLFVTNDAATILRELEVQHPAAKMIVMASHMQEQEVGDGTNFVLVFAGALLELAEELLR
  IGLSVSEVIEGYEIACRKAHEILPNLVCCSAKNLRDIDEVSSLLRTSIMSKQYGNEVFLA
  KLIAQACVSIFPDSGHFNVDNIRVCKILGSGISSSSVLHGMVFKKETEGDVTSVKDAKIA
  VYSCPFDGMITETKGTVLIKTAEELMNFSKGEENLMDAQVKAIADTGANVVVTGGKVADM
  ALHYANKYNIMLVRLNSKWDLRRLCKTVGATALPRLTPPVLEEMGHCDSVYLSEVGDTQV
  VVFKHEKEDGAISTIVLRGSTDNLMDDIERAVDDGVNTFKVLTRDKRLVPGGGATEIELA
  KQITSYGETCPGLEQYAIKKFAEAFEAIPRALAENSGVKANEVISKLYAVHQEGNKNVGL
  DIEAEVPAVKDMLEAGILDTYLGKYWAIKLATNAAVTVLRVDQIIMAKPAGGPKPPSGKK
  DWDDDQND
• 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. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. 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)
  BBSome-mediated cargo-targeting to cilium (R-HSA-5620922)
  Neutrophil degranulation (R-HSA-6798695)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Pancreatic cancer	DISJC981	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of T-complex protein 1 subunit theta (CCT8).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of T-complex protein 1 subunit theta (CCT8).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of T-complex protein 1 subunit theta (CCT8).	[7]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of T-complex protein 1 subunit theta (CCT8).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of T-complex protein 1 subunit theta (CCT8).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of T-complex protein 1 subunit theta (CCT8).	[10]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of T-complex protein 1 subunit theta (CCT8).	[11]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A affects the expression of T-complex protein 1 subunit theta (CCT8).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of T-complex protein 1 subunit theta (CCT8).	[9]

References

• [1] Chaperonin-containing Tcomplex protein 1 subunit 8 promotes cell migration and invasion in human esophageal squamous cell carcinoma by regulating -actin and -tubulin expression.Int J Oncol. 2018 Jun;52(6):2021-2030. doi: 10.3892/ijo.2018.4335. Epub 2018 Mar 27.
• [2] Overexpression of CCT8 and its significance for tumor cell proliferation, migration and invasion in glioma.Pathol Res Pract. 2015 Oct;211(10):717-25. doi: 10.1016/j.prp.2015.04.012. Epub 2015 May 19.
• [3] Glucose-regulated protein 94 mediates metastasis by CCT8 and the JNK pathway in hepatocellular carcinoma.Tumour Biol. 2016 Jun;37(6):8219-27. doi: 10.1007/s13277-015-4669-3. Epub 2015 Dec 30.
• [4] Differential secretome of pancreatic cancer cells in serum-containing conditioned medium reveals CCT8 as a new biomarker of pancreatic cancer invasion and metastasis.Cancer Cell Int. 2019 Oct 11;19:262. doi: 10.1186/s12935-019-0980-1. eCollection 2019.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] 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.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [9] 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.
• [10] 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.
• [11] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [12] Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes. J Biochem Mol Toxicol. 2016 Feb;30(2):71-9. doi: 10.1002/jbt.21738. Epub 2015 Aug 25.