Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH9193T)

• DOT Name: Putative methyltransferase C9orf114 (SPOUT1)
• Synonyms: EC 2.1.1.-; Centromere protein 32; CENP-32; Kinetochore-associated protein; SPOUT domain-containing methyltransferase 1
• Gene Name: SPOUT1
• UniProt ID: CI114_HUMAN
• PDB ID: 4RG1
• EC Number: 2.1.1.-
• Pfam ID: PF02598
• Sequence:
  MAERGRKRPCGPGEHGQRIEWRKWKQQKKEEKKKWKDLKLMKKLERQRAQEEQAKRLEEE
  EAAAEKEDRGRPYTLSVALPGSILDNAQSPELRTYLAGQIARACAIFCVDEIVVFDEEGQ
  DAKTVEGEFTGVGKKGQACVQLARILQYLECPQYLRKAFFPKHQDLQFAGLLNPLDSPHH
  MRQDEESEFREGIVVDRPTRPGHGSFVNCGMKKEVKIDKNLEPGLRVTVRLNQQQHPDCK
  TYHGKVVSSQDPRTKAGLYWGYTVRLASCLSAVFAEAPFQDGYDLTIGTSERGSDVASAQ
  LPNFRHALVVFGGLQGLEAGADADPNLEVAEPSVLFDLYVNTCPGQGSRTIRTEEAILIS
  LAALQPGLIQAGARHT
• Function: Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase. Also involved in chromosome alignment. May promote centrosome maturation probably by recruiting A-kinase anchor protein AKAP9 to centrosomes in early mitosis. Binds specifically to miRNA MIR145 hairpin, regulates MIR145 expression at a postranscriptional level.

Molecular Interaction Atlas (MIA) of This DOT

5 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 Putative methyltransferase C9orf114 (SPOUT1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Putative methyltransferase C9orf114 (SPOUT1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Putative methyltransferase C9orf114 (SPOUT1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Putative methyltransferase C9orf114 (SPOUT1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Putative methyltransferase C9orf114 (SPOUT1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Putative methyltransferase C9orf114 (SPOUT1).	[5]

References

• [1] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.
• [5] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [6] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.