Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7OU5J6)

• DOT Name: Tubulin gamma-1 chain
• Synonyms: Gamma-1-tubulin; Gamma-tubulin complex component 1; GCP-1
• Gene Name: TUBG1
• Related Disease:
  Lissencephaly spectrum disorders
  Complex cortical dysplasia with other brain malformations 4
• UniProt ID: TBG1_HUMAN
• PDB ID: 1Z5V; 1Z5W; 3CB2; 6V5V; 6V6S; 7AS4; 7QJ0; 7QJ1; 7QJ2; 7QJ3; 7QJ4; 7QJ5; 7QJ6; 7QJ7; 7QJ8; 7QJ9; 7QJA; 7QJB; 7QJC; 7QJD; 7QJE
• Pfam ID: PF00091 ; PF03953
• Sequence:
  MPREIITLQLGQCGNQIGFEFWKQLCAEHGISPEGIVEEFATEGTDRKDVFFYQADDEHY
  IPRAVLLDLEPRVIHSILNSPYAKLYNPENIYLSEHGGGAGNNWASGFSQGEKIHEDIFD
  IIDREADGSDSLEGFVLCHSIAGGTGSGLGSYLLERLNDRYPKKLVQTYSVFPNQDEMSD
  VVVQPYNSLLTLKRLTQNADCVVVLDNTALNRIATDRLHIQNPSFSQINQLVSTIMSAST
  TTLRYPGYMNNDLIGLIASLIPTPRLHFLMTGYTPLTTDQSVASVRKTTVLDVMRRLLQP
  KNVMVSTGRDRQTNHCYIAILNIIQGEVDPTQVHKSLQRIRERKLANFIPWGPASIQVAL
  SRKSPYLPSAHRVSGLMMANHTSISSLFERTCRQYDKLRKREAFLEQFRKEDMFKDNFDE
  MDTSREIVQQLIDEYHAATRPDYISWGTQEQ
• Function: Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lissencephaly spectrum disorders	DISBCZL7	Definitive	Autosomal dominant	[1]
Complex cortical dysplasia with other brain malformations 4	DIS7HHLH	Strong	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tubulin gamma-1 chain.	[3]

14 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 Tubulin gamma-1 chain.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tubulin gamma-1 chain.	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tubulin gamma-1 chain.	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tubulin gamma-1 chain.	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Tubulin gamma-1 chain.	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tubulin gamma-1 chain.	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tubulin gamma-1 chain.	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tubulin gamma-1 chain.	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Tubulin gamma-1 chain.	[11]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Tubulin gamma-1 chain.	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tubulin gamma-1 chain.	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tubulin gamma-1 chain.	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Tubulin gamma-1 chain.	[15]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Tubulin gamma-1 chain.	[16]

References

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• [2] Gene knockout analysis of two gamma-tubulin isoforms in mice. Dev Biol. 2005 Jun 15;282(2):361-73. doi: 10.1016/j.ydbio.2005.03.031.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [16] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.