Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MGUX9)

• DOT Name: T-complex protein 1 subunit alpha (TCP1)
• Synonyms: TCP-1-alpha; CCT-alpha
• Gene Name: TCP1
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Cataract
  Colorectal carcinoma
  Coronary atherosclerosis
  Coronary ischemia
  Fibromyalgia
  Gaucher disease
  Hepatocellular carcinoma
  Inherited retinal dystrophy
  Knee osteoarthritis
  Lipodystrophy
  Lymphoid neoplasm
  Lymphoma
  Myocardial ischemia
  Pediatric lymphoma
  Prostate cancer
  Prostate neoplasm
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Von hippel-lindau disease
  Adenocarcinoma
  Breast carcinoma
  Urinary bladder neoplasm
  Coronary heart disease
  Lung cancer
  Lung carcinoma
  Myocardial infarction
  Neoplasm
  Neurofibromatosis type 1
  Non-insulin dependent diabetes
  Squamous cell carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: TCPA_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:
  MEGPLSVFGDRSTGETIRSQNVMAAASIANIVKSSLGPVGLDKMLVDDIGDVTITNDGAT
  ILKLLEVEHPAAKVLCELADLQDKEVGDGTTSVVIIAAELLKNADELVKQKIHPTSVISG
  YRLACKEAVRYINENLIVNTDELGRDCLINAAKTSMSSKIIGINGDFFANMVVDAVLAIK
  YTDIRGQPRYPVNSVNILKAHGRSQMESMLISGYALNCVVGSQGMPKRIVNAKIACLDFS
  LQKTKMKLGVQVVITDPEKLDQIRQRESDITKERIQKILATGANVILTTGGIDDMCLKYF
  VEAGAMAVRRVLKRDLKRIAKASGATILSTLANLEGEETFEAAMLGQAEEVVQERICDDE
  LILIKNTKARTSASIILRGANDFMCDEMERSLHDALCVVKRVLESKSVVPGGGAVEAALS
  IYLENYATSMGSREQLAIAEFARSLLVIPNTLAVNAAQDSTDLVAKLRAFHNEAQVNPER
  KNLKWIGLDLSNGKPRDNKQAGVFEPTIVKVKSLKFATEAAITILRIDDLIKLHPESKDD
  KHGSYEDAVHSGALND
• 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)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)

Molecular Interaction Atlas (MIA) of This DOT

38 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]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Cataract	DISUD7SL	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[8]
Coronary ischemia	DISDJJ5G	Strong	Biomarker	[9]
Fibromyalgia	DISZJDS2	Strong	Biomarker	[10]
Gaucher disease	DISTW5JG	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[13]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[14]
Lipodystrophy	DIS3SGVD	Strong	Genetic Variation	[13]
Lymphoid neoplasm	DIS9S8BC	Strong	Biomarker	[2]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[8]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[15]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[15]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[16]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Biomarker	[17]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[18]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[19]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[20]
Lung cancer	DISCM4YA	Limited	Biomarker	[21]
Lung carcinoma	DISTR26C	Limited	Biomarker	[21]
Myocardial infarction	DIS655KI	Limited	Biomarker	[22]
Neoplasm	DISZKGEW	Limited	Biomarker	[23]
Neurofibromatosis type 1	DIS53JH9	Limited	Altered Expression	[24]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[25]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[26]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[27]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[27]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[27]

12 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 T-complex protein 1 subunit alpha (TCP1).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of T-complex protein 1 subunit alpha (TCP1).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of T-complex protein 1 subunit alpha (TCP1).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of T-complex protein 1 subunit alpha (TCP1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of T-complex protein 1 subunit alpha (TCP1).	[31]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of T-complex protein 1 subunit alpha (TCP1).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of T-complex protein 1 subunit alpha (TCP1).	[33]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of T-complex protein 1 subunit alpha (TCP1).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of T-complex protein 1 subunit alpha (TCP1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of T-complex protein 1 subunit alpha (TCP1).	[37]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of T-complex protein 1 subunit alpha (TCP1).	[39]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of T-complex protein 1 subunit alpha (TCP1).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of T-complex protein 1 subunit alpha (TCP1).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of T-complex protein 1 subunit alpha (TCP1).	[38]

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] Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis.Oncotarget. 2015 Dec 8;6(39):42105-17. doi: 10.18632/oncotarget.5870.
• [3] Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of ABCG2 drug transport.Pharmacol Res. 2017 Jul;121:184-193. doi: 10.1016/j.phrs.2017.04.025. Epub 2017 Apr 26.
• [4] Polymorphisms of the cholesterol 24-hydroxylase (CYP46A1) gene and the risk of Alzheimer's disease in a Chinese population.Int Psychogeriatr. 2006 Mar;18(1):37-45. doi: 10.1017/S1041610205003108.
• [5] Chaperonin Containing TCP-1 Protein Level in Breast Cancer Cells Predicts Therapeutic Application of a Cytotoxic Peptide.Clin Cancer Res. 2016 Sep 1;22(17):4366-79. doi: 10.1158/1078-0432.CCR-15-2502. Epub 2016 Mar 24.
• [6] Intraocular lens power calculation using a Placido disk-Scheimpflug tomographer in eyes that had previous myopic corneal excimer laser surgery.J Cataract Refract Surg. 2018 Aug;44(8):935-941. doi: 10.1016/j.jcrs.2018.05.018. Epub 2018 Jul 23.
• [7] Inhibition of cytosolic chaperonin CCT-1 expression depletes proliferation of colorectal carcinoma in vitro.J Surg Oncol. 2010 Oct 1;102(5):419-23. doi: 10.1002/jso.21625.
• [8] Impact of scan quality on the diagnostic performance of CCTA, SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve.J Cardiovasc Comput Tomogr. 2020 Jan-Feb;14(1):60-67. doi: 10.1016/j.jcct.2019.06.007. Epub 2019 Jun 12.
• [9] Computed tomography angiography-derived fractional flow reserve (CT-FFR) for the detection of myocardial ischemia with invasive fractional flow reserve as reference: systematic review and meta-analysis.Eur Radiol. 2020 Feb;30(2):712-725. doi: 10.1007/s00330-019-06470-8. Epub 2019 Nov 6.
• [10] Association of guanosine triphosphate cyclohydrolase 1 gene polymorphisms with fibromyalgia syndrome in a Korean population.J Rheumatol. 2013 Mar;40(3):316-22. doi: 10.3899/jrheum.120929. Epub 2013 Jan 15.
• [11] Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl.Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21665-70. doi: 10.1073/pnas.1014376107. Epub 2010 Nov 22.
• [12] Clinical and prognostic value of chaperonin containing T-complex 1 subunit 3 in hepatocellular carcinoma: A Study based on microarray and RNA-sequencing with 4272 cases.Pathol Res Pract. 2019 Jan;215(1):177-194. doi: 10.1016/j.prp.2018.11.006. Epub 2018 Nov 10.
• [13] Disease-linked mutations in the phosphatidylcholine regulatory enzyme CCT impair enzymatic activity and fold stability.J Biol Chem. 2019 Feb 1;294(5):1490-1501. doi: 10.1074/jbc.RA118.006457. Epub 2018 Dec 17.
• [14] Association of a functional polymorphism in the promoter region of TLR-3 with osteoarthritis: a two-stage case-control study.J Orthop Res. 2013 May;31(5):680-5. doi: 10.1002/jor.22291. Epub 2012 Dec 19.
• [15] Proteome analysis of human androgen-independent prostate cancer cell lines: variable metastatic potentials correlated with vimentin expression.Proteomics. 2007 Jun;7(12):1973-83. doi: 10.1002/pmic.200600643.
• [16] Coordinated expression of galectin-3 and caveolin-1 in thyroid cancer.J Pathol. 2012 Sep;228(1):56-66. doi: 10.1002/path.4041. Epub 2012 Jul 10.
• [17] Diverse effects of mutations in exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activity.Mol Cell Biol. 2002 Mar;22(6):1947-60. doi: 10.1128/MCB.22.6.1947-1960.2002.
• [18] Characterization and over-expression of chaperonin t-complex proteins in colorectal cancer.J Pathol. 2006 Nov;210(3):351-7. doi: 10.1002/path.2056.
• [19] Choline-phosphate cytidylyltransferase- as a possible predictor of survival and response to cisplatin neoadjuvant chemotherapy in urothelial cancer of the bladder.Scand J Urol. 2018 Jun;52(3):200-205. doi: 10.1080/21681805.2018.1439527. Epub 2018 Feb 23.
• [20] The evaluation of coronary artery-to-pulmonary artery fistula in adulthood on 256-slice CT coronary angiography: Comparison with coronary catheter angiography and transthoracic echocardiography.J Cardiovasc Comput Tomogr. 2019 Jan-Feb;13(1):75-80. doi: 10.1016/j.jcct.2018.10.013. Epub 2018 Oct 19.
• [21] Bioinformatics analysis of the prognostic value of CCT6A and associated signalling pathways in breast cancer.Mol Med Rep. 2019 May;19(5):4344-4352. doi: 10.3892/mmr.2019.10100. Epub 2019 Mar 28.
• [22] Regional differences of fat depot attenuation using non-contrast, contrast-enhanced, and delayed-enhanced cardiac CT.Acta Radiol. 2019 Apr;60(4):459-467. doi: 10.1177/0284185118787356. Epub 2018 Jul 31.
• [23] A novel vascular-targeting peptide for gastric cancer delivers low-dose TNF to normalize the blood vessels and improve the anti-cancer efficiency of 5-fluorouracil.Peptides. 2017 Nov;97:54-63. doi: 10.1016/j.peptides.2017.09.020. Epub 2017 Sep 29.
• [24] Heat shock factor 1 (HSF1)-targeted anticancer therapeutics: overview of current preclinical progress.Expert Opin Ther Targets. 2019 May;23(5):369-377. doi: 10.1080/14728222.2019.1602119. Epub 2019 Apr 7.
• [25] Association of HNF4 gene polymorphisms with susceptibility to type 2 diabetes.Mol Med Rep. 2016 Mar;13(3):2241-6. doi: 10.3892/mmr.2016.4780. Epub 2016 Jan 13.
• [26] CCT is a novel biomarker for diagnosis of laryngeal squamous cell cancer.Sci Rep. 2019 Aug 14;9(1):11823. doi: 10.1038/s41598-019-47895-x.
• [27] Effect of Interferon- on the Basal and the TNF-Stimulated Secretion of CXCL8 in Thyroid Cancer Cell Lines Bearing Either the RET/PTC Rearrangement Or the BRAF V600e Mutation.Mediators Inflamm. 2016;2016:8512417. doi: 10.1155/2016/8512417. Epub 2016 Jul 31.
• [28] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [29] Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci. 2011 Mar;120(1):109-22.
• [30] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [31] 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.
• [32] 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.
• [33] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [34] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] 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.
• [39] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [40] 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.