Details of Drug Off-Target (DOT)

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

• DOT Name: Translocon-associated protein subunit delta (SSR4)
• Synonyms: TRAP-delta; Signal sequence receptor subunit delta; SSR-delta
• Gene Name: SSR4
• Related Disease:
  Congenital disorder of glycosylation
  SSR4-congenital disorder of glycosylation
• UniProt ID: SSRD_HUMAN
• PDB ID: 8B6L
• Pfam ID: PF05404
• Sequence:
  MAAMASLGALALLLLSSLSRCSAEACLEPQITPSYYTTSDAVISTETVFIVEISLTCKNR
  VQNMALYADVGGKQFPVTRGQDVGRYQVSWSLDHKSAHAGTYEVRFFDEESYSLLRKAQR
  NNEDISIIPPLFTVSVDHRGTWNGPWVSTEVLAAAIGLVIYYLAFSAKSHIQA
• Function: TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway: SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital disorder of glycosylation	DIS400QP	Strong	Genetic Variation	[1]
SSR4-congenital disorder of glycosylation	DISQBQCX	Strong	X-linked	[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 Translocon-associated protein subunit delta (SSR4).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Translocon-associated protein subunit delta (SSR4).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Translocon-associated protein subunit delta (SSR4).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Translocon-associated protein subunit delta (SSR4).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Translocon-associated protein subunit delta (SSR4).	[7]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Translocon-associated protein subunit delta (SSR4).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Translocon-associated protein subunit delta (SSR4).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Translocon-associated protein subunit delta (SSR4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Translocon-associated protein subunit delta (SSR4).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Translocon-associated protein subunit delta (SSR4).	[12]

References

• [1] Expanding the Molecular and Clinical Phenotype of SSR4-CDG.Hum Mutat. 2015 Nov;36(11):1048-51. doi: 10.1002/humu.22856. Epub 2015 Aug 27.
• [2] A new congenital disorder of glycosylation caused by a mutation in SSR4, the signal sequence receptor 4 protein of the TRAP complex. Hum Mol Genet. 2014 Mar 15;23(6):1602-5. doi: 10.1093/hmg/ddt550. Epub 2013 Nov 11.
• [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] 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.
• [7] 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.
• [8] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [11] 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.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.