Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPV73W7)

• DOT Name: Signal recognition particle subunit SRP72 (SRP72)
• Synonyms: SRP72; Signal recognition particle 72 kDa protein
• Gene Name: SRP72
• Related Disease:
  Advanced cancer
  Aplastic anemia
  Autosomal dominant aplasia and myelodysplasia
  Bone marrow failure syndrome
  Breast neoplasm
  Cholestasis
  Li-Fraumeni syndrome
  Myelodysplastic syndrome
  Acute myelogenous leukaemia
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: SRP72_HUMAN
• PDB ID: 5M72; 5M73; 5WRV; 5WRW; 7NFX
• Pfam ID: PF08492 ; PF17004 ; PF13181
• Sequence:
  MASGGSGGVSVPALWSEVNRYGQNGDFTRALKTVNKILQINKDDVTALHCKVVCLIQNGS
  FKEALNVINTHTKVLANNSLSFEKAYCEYRLNRIENALKTIESANQQTDKLKELYGQVLY
  RLERYDECLAVYRDLVRNSQDDYDEERKTNLSAVVAAQSNWEKVVPENLGLQEGTHELCY
  NTACALIGQGQLNQAMKILQKAEDLCRRSLSEDTDGTEEDPQAELAIIHGQMAYILQLQG
  RTEEALQLYNQIIKLKPTDVGLLAVIANNIITINKDQNVFDSKKKVKLTNAEGVEFKLSK
  KQLQAIEFNKALLAMYTNQAEQCRKISASLQSQSPEHLLPVLIQAAQLCREKQHTKAIEL
  LQEFSDQHPENAAEIKLTMAQLKISQGNISKACLILRSIEELKHKPGMVSALVTMYSHEE
  DIDSAIEVFTQAIQWYQNHQPKSPAHLSLIREAANFKLKYGRKKEAISDLQQLWKQNPKD
  IHTLAQLISAYSLVDPEKAKALSKHLPSSDSMSLKVDVEALENSAGATYIRKKGGKVTGD
  SQPKEQGQGDLKKKKKKKKGKLPKNYDPKVTPDPERWLPMRERSYYRGRKKGKKKDQIGK
  GTQGATAGASSELDASKTVSSPPTSPRPGSAATVSASTSNIIPPRHQKPAGAPATKKKQQ
  QKKKKGGKGGW
• Function: Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER. The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER. Binds the signal recognition particle RNA (7SL RNA) in presence of SRP68. Can bind 7SL RNA with low affinity. The SRP complex possibly participates in the elongation arrest function.
• KEGG Pathway: Protein export (hsa03060)
• Reactome Pathway: SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Aplastic anemia	DISJRSC0	Strong	Genetic Variation	[2]
Autosomal dominant aplasia and myelodysplasia	DISLQO9K	Strong	Autosomal dominant	[3]
Bone marrow failure syndrome	DISVUY1J	Strong	Genetic Variation	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Cholestasis	DISDJJWE	Strong	Biomarker	[6]
Li-Fraumeni syndrome	DISR64XA	Strong	Genetic Variation	[1]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Moderate	Autosomal dominant	[7]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[8]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[8]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[8]

13 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 Signal recognition particle subunit SRP72 (SRP72).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Signal recognition particle subunit SRP72 (SRP72).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Signal recognition particle subunit SRP72 (SRP72).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Signal recognition particle subunit SRP72 (SRP72).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal recognition particle subunit SRP72 (SRP72).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Signal recognition particle subunit SRP72 (SRP72).	[14]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Signal recognition particle subunit SRP72 (SRP72).	[15]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Signal recognition particle subunit SRP72 (SRP72).	[16]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Signal recognition particle subunit SRP72 (SRP72).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Signal recognition particle subunit SRP72 (SRP72).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal recognition particle subunit SRP72 (SRP72).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Signal recognition particle subunit SRP72 (SRP72).	[21]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Signal recognition particle subunit SRP72 (SRP72).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Signal recognition particle subunit SRP72 (SRP72).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Signal recognition particle subunit SRP72 (SRP72).	[19]

References

• [1] Hereditary myeloid malignancies.Best Pract Res Clin Haematol. 2019 Jun;32(2):163-176. doi: 10.1016/j.beha.2019.05.001. Epub 2019 May 3.
• [2] Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes.Eur J Haematol. 2019 Oct;103(4):319-328. doi: 10.1111/ejh.13286. Epub 2019 Jul 26.
• [3] Exome sequencing identifies autosomal-dominant SRP72 mutations associated with familial aplasia and myelodysplasia. Am J Hum Genet. 2012 May 4;90(5):888-92. doi: 10.1016/j.ajhg.2012.03.020. Epub 2012 Apr 26.
• [4] Genetic predisposition syndromes: when should they be considered in the work-up of MDS?.Best Pract Res Clin Haematol. 2015 Mar;28(1):55-68. doi: 10.1016/j.beha.2014.11.004. Epub 2014 Nov 12.
• [5] Depletion of signal recognition particle 72kDa increases radiosensitivity.Cancer Biol Ther. 2017 Jun 3;18(6):425-432. doi: 10.1080/15384047.2017.1323587. Epub 2017 May 11.
• [6] Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices.Chem Res Toxicol. 2016 Mar 21;29(3):342-51. doi: 10.1021/acs.chemrestox.5b00491. Epub 2016 Mar 9.
• [7] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [8] An integrated analysis of cancer genes in thyroid cancer.Oncol Rep. 2016 Feb;35(2):962-70. doi: 10.3892/or.2015.4466. Epub 2015 Dec 1.
• [9] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [10] 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.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] 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.
• [14] 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.
• [15] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [16] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [17] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] 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.
• [20] 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.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.