Details of Drug Off-Target (DOT)

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

• DOT Name: Signal recognition particle receptor subunit beta (SRPRB)
• Synonyms: SR-beta; Protein APMCF1
• Gene Name: SRPRB
• Related Disease:
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Glioma
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: SRPRB_HUMAN
• PDB ID: 7NFX
• Pfam ID: PF09439
• Sequence:
  MASADSRRVADGGGAGGTFQPYLDTLRQELQQTDPTLLSVVVAVLAVLLTLVFWKLIRSR
  RSSQRAVLLVGLCDSGKTLLFVRLLTGLYRDTQTSITDSCAVYRVNNNRGNSLTLIDLPG
  HESLRLQFLERFKSSARAIVFVVDSAAFQREVKDVAEFLYQVLIDSMGLKNTPSFLIACN
  KQDIAMAKSAKLIQQQLEKELNTLRVTRSAAPSTLDSSSTAPAQLGKKGKEFEFSQLPLK
  VEFLECSAKGGRGDVGSADIQDLEKWLAKIA
• Function: Component of the signal recognition particle (SRP) complex receptor (SR). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system. May mediate the membrane association of SR.
• KEGG Pathway: Protein export (hsa03060)
• Reactome Pathway:
  XBP1(S) activates chaperone genes (R-HSA-381038)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

2 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 Signal recognition particle receptor subunit beta (SRPRB).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Signal recognition particle receptor subunit beta (SRPRB).	[13]

13 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 Signal recognition particle receptor subunit beta (SRPRB).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Signal recognition particle receptor subunit beta (SRPRB).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Signal recognition particle receptor subunit beta (SRPRB).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Signal recognition particle receptor subunit beta (SRPRB).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Signal recognition particle receptor subunit beta (SRPRB).	[17]

References

• [1] Subcellular localization of APMCF1 and its biological significance of expression pattern in normal and malignant human tissues.J Exp Clin Cancer Res. 2009 Aug 9;28(1):111. doi: 10.1186/1756-9966-28-111.
• [2] Isolation of a novel member of small G protein superfamily and its expression in colon cancer.World J Gastroenterol. 2003 Aug;9(8):1719-24. doi: 10.3748/wjg.v9.i8.1719.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [16] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.