Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN1URWQ)

• DOT Name: Gamma-tubulin complex component 4
• Synonyms: GCP-4; hGCP4; Gamma-ring complex protein 76 kDa; h76p; hGrip76
• Gene Name: TUBGCP4
• Related Disease:
  Microcephaly and chorioretinopathy 3
  Microcephaly and chorioretinopathy 1
• UniProt ID: GCP4_HUMAN
• PDB ID: 3RIP; 6V69; 6V6S; 7AS4; 7QJ0; 7QJ1; 7QJ2; 7QJ3; 7QJ4; 7QJ5; 7QJ6; 7QJ7; 7QJ8; 7QJ9; 7QJA; 7QJB; 7QJC; 7QJD; 7QJE
• Pfam ID: PF04130 ; PF17681
• Sequence:
  MIHELLLALSGYPGSIFTWNKRSGLQVSQDFPFLHPSETSVLNRLCRLGTDYIRFTEFIE
  QYTGHVQQQDHHPSQQGQGGLHGIYLRAFCTGLDSVLQPYRQALLDLEQEFLGDPHLSIS
  HVNYFLDQFQLLFPSVMVVVEQIKSQKIHGCQILETVYKHSCGGLPPVRSALEKILAVCH
  GVMYKQLSAWMLHGLLLDQHEEFFIKQGPSSGNVSAQPEEDEEDLGIGGLTGKQLRELQD
  LRLIEEENMLAPSLKQFSLRVEILPSYIPVRVAEKILFVGESVQMFENQNVNLTRKGSIL
  KNQEDTFAAELHRLKQQPLFSLVDFEQVVDRIRSTVAEHLWKLMVEESDLLGQLKIIKDF
  YLLGRGELFQAFIDTAQHMLKTPPTAVTEHDVNVAFQQSAHKVLLDDDNLLPLLHLTIEY
  HGKEHKADATQAREGPSRETSPREAPASGWAALGLSYKVQWPLHILFTPAVLEKYNVVFK
  YLLSVRRVQAELQHCWALQMQRKHLKSNQTDAIKWRLRNHMAFLVDNLQYYLQVDVLESQ
  FSQLLHQINSTRDFESIRLAHDHFLSNLLAQSFILLKPVFHCLNEILDLCHSFCSLVSQN
  LGPLDERGAAQLSILVKGFSRQSSLLFKILSSVRNHQINSDLAQLLLRLDYNKYYTQAGG
  TLGSFGM
• Function: Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microcephaly and chorioretinopathy 3	DISBTP8M	Strong	Autosomal recessive	[1]
Microcephaly and chorioretinopathy 1	DISGSTH2	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Gamma-tubulin complex component 4.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Gamma-tubulin complex component 4.	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Gamma-tubulin complex component 4.	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Gamma-tubulin complex component 4.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Gamma-tubulin complex component 4.	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Gamma-tubulin complex component 4.	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Gamma-tubulin complex component 4.	[8]

References

• [1] Mutations in TUBGCP4 alter microtubule organization via the -tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy. Am J Hum Genet. 2015 Apr 2;96(4):666-74. doi: 10.1016/j.ajhg.2015.02.011. Epub 2015 Mar 26.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.