Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX9RG3F)

DOT Name	Pseudouridylate synthase RPUSD4, mitochondrial (RPUSD4)
Synonyms	EC 5.4.99.-; RNA pseudouridylate synthase domain-containing protein 4
Gene Name	RPUSD4
UniProt ID	RUSD4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5UBA
EC Number	5.4.99.-
Pfam ID	PF00849
Sequence	MAAPRWSASGPWIRGNGQGCGSLFTLVSKPFCAAAAASTAINAQRLAEKLRAQKREQDTK KEPVSTNAVQRRVQEIVRFTRQLQRVHPNVLAKALTRGILHQDKNLVVINKPYGLPVHGG PGVQLCITDVLPILAKMLHGHKAEPLHLCHRLDKETTGVMVLAWDKDMAHQVQELFRTRQ VVKKYWAITVHVPMPSAGVVDIPIVEKEAQGQQQHHKMTLSPSYRMDDGKMVKVRRSRNA QVAVTQYQVLSSTLSSALVELQPITGIKHQLRVHLSFGLDCPILGDHKYSDWNRLAPQKL SVGTLKKLGLEQSKARYIPLHLHARQLILPALGSGKEELNLVCKLPRFFVHSLHRLRLEM PNEDQNENNEAKCLGAQ
Function	Catalyzes uridine to pseudouridine isomerization (pseudouridylation) of different mitochondrial RNA substrates. Acts on position 1397 in 16S mitochondrial ribosomal RNA (16S mt-rRNA). This modification is required for the assembly of 16S mt-rRNA into a functional mitochondrial ribosome. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA, controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation. Acts on position 39 in mitochondrial tRNA(Phe). Also catalyzes pseudouridylation of mRNAs in nucleus: acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions. Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3'-end processing.

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pseudouridylate synthase RPUSD4, mitochondrial (RPUSD4).	[1]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pseudouridylate synthase RPUSD4, mitochondrial (RPUSD4).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pseudouridylate synthase RPUSD4, mitochondrial (RPUSD4).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pseudouridylate synthase RPUSD4, mitochondrial (RPUSD4).	[4]
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References

1	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.
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	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.