Details of Drug Off-Target (DOT)

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

• DOT Name: Gamma-tubulin complex component 2
• Synonyms: GCP-2; hGCP2; Gamma-ring complex protein 103 kDa; h103p; hGrip103; Spindle pole body protein Spc97 homolog; hSpc97
• Gene Name: TUBGCP2
• Related Disease:
  Norman-Roberts syndrome
  Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures
• UniProt ID: GCP2_HUMAN
• PDB ID: 6V6B; 6V6S; 6X0V; 7AS4; 7QJ0; 7QJ1; 7QJ2; 7QJ3; 7QJ4; 7QJ5; 7QJ6; 7QJ7; 7QJ8; 7QJ9; 7QJA; 7QJB; 7QJC; 7QJD
• Pfam ID: PF04130 ; PF17681
• Sequence:
  MSEFRIHHDVNELLSLLRVHGGDGAEVYIDLLQKNRTPYVTTTVSAHSAKVKIAEFSRTP
  EDFLKKYDELKSKNTRNLDPLVYLLSKLTEDKETLQYLQQNAKERAELAAAAVGSSTTSI
  NVPAAASKISMQELEELRKQLGSVATGSTLQQSLELKRKMLRDKQNKKNSGQHLPIFPAW
  VYERPALIGDFLIGAGISTDTALPIGTLPLASQESAVVEDLLYVLVGVDGRYVSAQPLAG
  RQSRTFLVDPNLDLSIRELVHRILPVAASYSAVTRFIEEKSSFEYGQVNHALAAAMRTLV
  KEHLILVSQLEQLHRQGLLSLQKLWFYIQPAMRTMDILASLATSVDKGECLGGSTLSLLH
  DRSFSYTGDSQAQELCLYLTKAASAPYFEVLEKWIYRGIIHDPYSEFMVEEHELRKERIQ
  EDYNDKYWDQRYTIVQQQIPSFLQKMADKILSTGKYLNVVRECGHDVTCPVAKEIIYTLK
  ERAYVEQIEKAFNYASKVLLDFLMEEKELVAHLRSIKRYFLMDQGDFFVHFMDLAEEELR
  KPVEDITPPRLEALLELALRMSTANTDPFKDDLKIDLMPHDLITQLLRVLAIETKQEKAM
  AHADPTELALSGLEAFSFDYIVKWPLSLIINRKALTRYQMLFRHMFYCKHVERQLCSVWI
  SNKTAKQHSLHSAQWFAGAFTLRQRMLNFVQNIQYYMMFEVMEPTWHILEKNLKSASNID
  DVLGHHTGFLDTCLKDCMLTNPELLKVFSKLMSVCVMFTNCMQKFTQSMKLDGELGGQTL
  EHSTVLGLPAGAEERARKELARKHLAEHADTVQLVSGFEATINKFDKNFSAHLLDLLARL
  SIYSTSDCEHGMASVISRLDFNGFYTERLERLSAERSQKATPQVPVLRGPPAPAPRVAVT
  AQ
• Function: Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome. Plays a role in neuronal migration.
• 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
Norman-Roberts syndrome	DISUXOK0	Strong	Autosomal recessive	[1]
Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures	DISZ431L	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Gamma-tubulin complex component 2.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Gamma-tubulin complex component 2.	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gamma-tubulin complex component 2.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Gamma-tubulin complex component 2.	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Gamma-tubulin complex component 2.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Gamma-tubulin complex component 2.	[8]

References

• [1] Bi-allelic Pathogenic Variants in TUBGCP2 Cause Microcephaly and Lissencephaly Spectrum Disorders. Am J Hum Genet. 2019 Nov 7;105(5):1005-1015. doi: 10.1016/j.ajhg.2019.09.017. Epub 2019 Oct 17.
• [2] Effect of inbreeding on intellectual disability revisited by trio sequencing. Clin Genet. 2019 Jan;95(1):151-159. doi: 10.1111/cge.13463. Epub 2018 Nov 19.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.