Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFSO3XV)

• DOT Name: Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1)
• Gene Name: CSTPP1
• UniProt ID: CSTP1_HUMAN
• Sequence:
  MLSPERLALPDYEYLAQRHVLTYMEDAVCQLLENREDISQYGIARFFTEYFNSVCQGTHI
  LFREFSFVQATPHNRVSFLRAFWRCFRTVGKNGDLLTMKEYHCLLQLLCPDFPLELTQKA
  ARIVLMDDAMDCLMSFSDFLFAFQIQFYYSEFLDSVAAIYEDLLSGKNPNTVIVPTSSSG
  QHRQRPALGGAGTLEGVEASLFYQCLENLCDRHKYSCPPPALVKEALSNVQRLTFYGFLM
  ALSKHRGINQALGALPDKGDLMHDPAMDEELERLLAQVPGLVNSVTASPEASCLPSRTPP
  RVGSPWRPLHHSRKVDGESDGSTEETDESET
• Function: Regulator of the tubulin polyglutamylase complex (TPGC) that controls cytoskeletal organization, nuclear shape, and cilium disassembly by balancing microtubule and actin assembly. Regulates the assembly and stability of the TPGC and thereby modulates polyglutamylation of the microtubule, which antagonizes MAP4 binding.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1) affects the response to substance of Topotecan.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 (CSTPP1).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.