Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW1VV4E)

• DOT Name: T-complex protein 1 subunit beta (CCT2)
• Synonyms: TCP-1-beta; CCT-beta
• Gene Name: CCT2
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Advanced cancer
  Alzheimer disease
  Huntington disease
  Leber congenital amaurosis 1
  Leber congenital amaurosis 9
  Myocardial infarction
  Neoplasm
  Osteoporosis
  Prostate cancer
  Prostate carcinoma
  Type-1/2 diabetes
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Diabetic kidney disease
  Hyperglycemia
  Leber congenital amaurosis
  Lung cancer
  Lung carcinoma
  Myotonic dystrophy type 1
  Nephropathy
  Small-cell lung cancer
• UniProt ID: TCPB_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:
  MASLSLAPVNIFKAGADEERAETARLTSFIGAIAIGDLVKSTLGPKGMDKILLSSGRDAS
  LMVTNDGATILKNIGVDNPAAKVLVDMSRVQDDEVGDGTTSVTVLAAELLREAESLIAKK
  IHPQTIIAGWREATKAAREALLSSAVDHGSDEVKFRQDLMNIAGTTLSSKLLTHHKDHFT
  KLAVEAVLRLKGSGNLEAIHIIKKLGGSLADSYLDEGFLLDKKIGVNQPKRIENAKILIA
  NTGMDTDKIKIFGSRVRVDSTAKVAEIEHAEKEKMKEKVERILKHGINCFINRQLIYNYP
  EQLFGAAGVMAIEHADFAGVERLALVTGGEIASTFDHPELVKLGSCKLIEEVMIGEDKLI
  HFSGVALGEACTIVLRGATQQILDEAERSLHDALCVLAQTVKDSRTVYGGGCSEMLMAHA
  VTQLANRTPGKEAVAMESYAKALRMLPTIIADNAGYDSADLVAQLRAAHSEGNTTAGLDM
  REGTIGDMAILGITESFQVKRQVLLSAAEAAEVILRVDNIIKAAPRKRVPDHHPC
• 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)
  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

24 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]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Huntington disease	DISQPLA4	Strong	Genetic Variation	[4]
Leber congenital amaurosis 1	DISY2B33	Strong	Genetic Variation	[5]
Leber congenital amaurosis 9	DIS35YGW	Strong	Autosomal recessive	[6]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Osteoporosis	DISF2JE0	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[12]
Diabetic kidney disease	DISJMWEY	Limited	Biomarker	[13]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[13]
Leber congenital amaurosis	DISMGH8F	Limited	Autosomal recessive	[6]
Lung cancer	DISCM4YA	Limited	Altered Expression	[14]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[14]
Myotonic dystrophy type 1	DISJC0OX	Limited	Altered Expression	[13]
Nephropathy	DISXWP4P	Limited	Biomarker	[13]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[14]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	T-complex protein 1 subunit beta (CCT2) decreases the response to substance of Artesunate.	[32]
Sulforaphane	DMQY3L0	Investigative	T-complex protein 1 subunit beta (CCT2) affects the binding of Sulforaphane.	[33]

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 T-complex protein 1 subunit beta (CCT2).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of T-complex protein 1 subunit beta (CCT2).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of T-complex protein 1 subunit beta (CCT2).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of T-complex protein 1 subunit beta (CCT2).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of T-complex protein 1 subunit beta (CCT2).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of T-complex protein 1 subunit beta (CCT2).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of T-complex protein 1 subunit beta (CCT2).	[21]
Menadione	DMSJDTY	Approved	Menadione affects the expression of T-complex protein 1 subunit beta (CCT2).	[21]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of T-complex protein 1 subunit beta (CCT2).	[22]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of T-complex protein 1 subunit beta (CCT2).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of T-complex protein 1 subunit beta (CCT2).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of T-complex protein 1 subunit beta (CCT2).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of T-complex protein 1 subunit beta (CCT2).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of T-complex protein 1 subunit beta (CCT2).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of T-complex protein 1 subunit beta (CCT2).	[29]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of T-complex protein 1 subunit beta (CCT2).	[30]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of T-complex protein 1 subunit beta (CCT2).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of T-complex protein 1 subunit beta (CCT2).	[26]

References

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• [2] 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.
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