Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5D452X)

DOT Name	T-complex protein 1 subunit delta (CCT4)
Synonyms	TCP-1-delta; CCT-delta; Stimulator of TAR RNA-binding
Gene Name	CCT4
Related Disease	Neoplasm ( ) Advanced cancer ( ) B-cell lymphoma ( ) Breast cancer ( ) Colon cancer ( ) Colon carcinoma ( ) Epithelial ovarian cancer ( ) Glioma ( ) Hepatocellular carcinoma ( ) Large cell lymphoma ( ) Lung adenocarcinoma ( ) Lung carcinoma ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pachyonychia congenita 3 ( ) Peripheral sensory neuropathies ( ) Prostate cancer ( ) Prostate carcinoma ( ) T-cell acute lymphoblastic leukaemia ( ) Triple negative breast cancer ( ) Breast carcinoma ( ) Cervical carcinoma ( ) Pancreatic cancer ( ) Type-1/2 diabetes ( ) Breast adenocarcinoma ( ) Squamous cell carcinoma ( )
UniProt ID	TCPD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
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	MPENVAPRSGATAGAAGGRGKGAYQDRDKPAQIRFSNISAAKAVADAIRTSLGPKGMDKM IQDGKGDVTITNDGATILKQMQVLHPAARMLVELSKAQDIEAGDGTTSVVIIAGSLLDSC TKLLQKGIHPTIISESFQKALEKGIEILTDMSRPVELSDRETLLNSATTSLNSKVVSQYS SLLSPMSVNAVMKVIDPATATSVDLRDIKIVKKLGGTIDDCELVEGLVLTQKVSNSGITR VEKAKIGLIQFCLSAPKTDMDNQIVVSDYAQMDRVLREERAYILNLVKQIKKTGCNVLLI QKSILRDALSDLALHFLNKMKIMVIKDIEREDIEFICKTIGTKPVAHIDQFTADMLGSAE LAEEVNLNGSGKLLKITGCASPGKTVTIVVRGSNKLVIEEAERSIHDALCVIRCLVKKRA LIAGGGAPEIELALRLTEYSRTLSGMESYCVRAFADAMEVIPSTLAENAGLNPISTVTEL RNRHAQGEKTAGINVRKGGISNILEELVVQPLLVSVSALTLATETVRSILKIDDVVNTR
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 ) Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957 )

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Large cell lymphoma	DISYZHCP	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[6]
Pachyonychia congenita 3	DISZLC6C	Strong	Biomarker	[11]
Peripheral sensory neuropathies	DISYWI6M	Strong	Genetic Variation	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[13]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[4]
Cervical carcinoma	DIST4S00	moderate	Genetic Variation	[14]
Pancreatic cancer	DISJC981	moderate	Biomarker	[15]
Type-1/2 diabetes	DISIUHAP	Disputed	Biomarker	[16]
Breast adenocarcinoma	DISMPHJ0	Limited	Genetic Variation	[17]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[9]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 delta (CCT4).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of T-complex protein 1 subunit delta (CCT4).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of T-complex protein 1 subunit delta (CCT4).	[27]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of T-complex protein 1 subunit delta (CCT4).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of T-complex protein 1 subunit delta (CCT4).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of T-complex protein 1 subunit delta (CCT4).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of T-complex protein 1 subunit delta (CCT4).	[22]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of T-complex protein 1 subunit delta (CCT4).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of T-complex protein 1 subunit delta (CCT4).	[25]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of T-complex protein 1 subunit delta (CCT4).	[28]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of T-complex protein 1 subunit delta (CCT4).	[29]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of T-complex protein 1 subunit delta (CCT4).	[30]
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⏷ Show the Full List of 9 Drug(s)

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of T-complex protein 1 subunit delta (CCT4).	[24]
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References

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9	Anti-proliferative effect of 8-tigloyloxyhirsutinolide-13-O-acetate (8TGH) isolated from Vernonia cinerea on oral squamous cell carcinoma through inhibition of STAT3 and STAT2 phosphorylation.Phytomedicine. 2019 Jan;52:238-246. doi: 10.1016/j.phymed.2018.09.211. Epub 2018 Sep 26.
10	HNRNP Q suppresses polyglutamine huntingtin aggregation by post-transcriptional regulation of vaccinia-related kinase 2.J Neurochem. 2019 May;149(3):413-426. doi: 10.1111/jnc.14638. Epub 2019 Jan 4.
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12	Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. J Med Genet. 2006 May;43(5):441-3. doi: 10.1136/jmg.2005.039230. Epub 2006 Jan 6.
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14	Assessment of free radical scavenging and anti-proliferative activities of Tinospora cordifolia Miers (Willd).BMC Complement Altern Med. 2017 Sep 11;17(1):457. doi: 10.1186/s12906-017-1953-3.
15	Synthesis of novel tetrazole containing hybrid ciprofloxacin and pipemidic acid analogues and preliminary biological evaluation of their antibacterial and antiproliferative activity.Mol Divers. 2018 Feb;22(1):83-93. doi: 10.1007/s11030-017-9795-y. Epub 2017 Nov 14.
16	Endoplasmic reticulum stress activation in adipose tissue induces metabolic syndrome in individuals with familial partial lipodystrophy of the Dunnigan type.Diabetol Metab Syndr. 2018 Feb 9;10:6. doi: 10.1186/s13098-017-0301-6. eCollection 2018.
17	Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction.Anticancer Agents Med Chem. 2018;18(15):2124-2130. doi: 10.2174/1871520618666180409155520.
18	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.
19	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
20	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.
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30	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.