Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NMYTY)

• DOT Name: Signal recognition particle receptor subunit alpha (SRPRA)
• Synonyms: SR-alpha; Docking protein alpha; DP-alpha
• Gene Name: SRPRA
• Related Disease:
  Schizophrenia
  Complex neurodevelopmental disorder
• UniProt ID: SRPRA_HUMAN
• PDB ID: 2FH5; 2GO5; 5L3Q; 6Y32; 7NFX
• Pfam ID: PF04086 ; PF00448 ; PF02881
• Sequence:
  MLDFFTIFSKGGLVLWCFQGVSDSCTGPVNALIRSVLLQERGGNNSFTHEALTLKYKLDN
  QFELVFVVGFQKILTLTYVDKLIDDVHRLFRDKYRTEIQQQSALSLLNGTFDFQNDFLRL
  LREAEESSKIRAPTTMKKFEDSEKAKKPVRSMIETRGEKPKEKAKNSKKKGAKKEGSDGP
  LATSKPVPAEKSGLPVGPENGVELSKEELIRRKREEFIQKHGRGMEKSNKSTKSDAPKEK
  GKKAPRVWELGGCANKEVLDYSTPTTNGTPEAALSEDINLIRGTGSGGQLQDLDCSSSDD
  EGAAQNSTKPSATKGTLGGMFGMLKGLVGSKSLSREDMESVLDKMRDHLIAKNVAADIAV
  QLCESVANKLEGKVMGTFSTVTSTVKQALQESLVQILQPQRRVDMLRDIMDAQRRQRPYV
  VTFCGVNGVGKSTNLAKISFWLLENGFSVLIAACDTFRAGAVEQLRTHTRRLSALHPPEK
  HGGRTMVQLFEKGYGKDAAGIAMEAIAFARNQGFDVVLVDTAGRMQDNAPLMTALAKLIT
  VNTPDLVLFVGEALVGNEAVDQLVKFNRALADHSMAQTPRLIDGIVLTKFDTIDDKVGAA
  ISMTYITSKPIVFVGTGQTYCDLRSLNAKAVVAALMKA
• 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. Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SRP subunit SRP54. SRP receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Signal recognition particle receptor subunit alpha (SRPRA) affects the response to substance of Paclitaxel.	[18]

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 Signal recognition particle receptor subunit alpha (SRPRA).	[3]

14 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 alpha (SRPRA).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[8]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[11]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Signal recognition particle receptor subunit alpha (SRPRA).	[17]

References

• [1] The complex relationship between self-reported 'personal recovery' and clinical recovery in schizophrenia.Schizophr Res. 2018 Feb;192:108-112. doi: 10.1016/j.schres.2017.04.040. Epub 2017 May 9.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [17] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [18] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.