Details of Drug Off-Target (DOT)

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

DOT Name Steroid receptor RNA activator 1 (SRA1)
Synonyms Steroid receptor RNA activator protein; SRAP
Gene Name SRA1
Related Disease
Bone osteosarcoma ( )
Endometrial carcinoma ( )
Osteosarcoma ( )
Atrial fibrillation ( )
B-cell neoplasm ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Colitis ( )
Endometriosis ( )
Epithelial neoplasm ( )
Epithelial ovarian cancer ( )
Fatty liver disease ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Liver cancer ( )
Neoplasm ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Promyelocytic leukaemia ( )
Stroke ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Alzheimer disease ( )
Cardiovascular disease ( )
Chronic obstructive pulmonary disease ( )
Endometrial cancer ( )
High blood pressure ( )
Hypogonadotropic hypogonadism 7 with or without anosmia ( )
Lung carcinoma ( )
Ovarian cancer ( )
Prostate cancer ( )
Advanced cancer ( )
Asthma ( )
Campomelic dysplasia ( )
Castration-resistant prostate carcinoma ( )
Cholangiocarcinoma ( )
Clear cell renal carcinoma ( )
Heparin-induced thrombocytopenia ( )
Intellectual disability ( )
Lung cancer ( )
Melanoma ( )
Nervous system disease ( )
Prostate carcinoma ( )
Renal cell carcinoma ( )
Schizophrenia ( )
UniProt ID
SRA1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2MGX; 4NBO
Pfam ID
PF07304
Sequence
MAELYVKPGNKERGWNDPPQFSYGLQTQAGGPRRSLLTKRVAAPQDGSPRVPASETSPGP
PPMGPPPPSSKAPRSPPVGSGPASGVEPTSFPVESEAVMEDVLRPLEQALEDCRGHTRKQ
VCDDISRRLALLQEQWAGGKLSIPVKKRMALLVQELSSHRWDAADDIHRSLMVDHVTEVS
QWMVGVKRLIAEKRSLFSEEAANEEKSAATAEKNHTIPGFQQAS
Function
Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N-terminal domain (AF-1) of steroid receptors. Also mediates transcriptional coactivation of steroid receptors ligand-dependently through the steroid-binding domain (AF-2). Enhances cellular proliferation and differentiation and promotes apoptosis in vivo. May play a role in tumorigenesis.
Tissue Specificity
Highly expressed in liver and skeletal muscle and to a lesser extent in brain. Also expressed in both normal and tumorigenic breast epithelial cell lines. Significantly up-regulated in human tumors of the breast, ovary, and uterus.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bone osteosarcoma DIST1004 Definitive Altered Expression [1]
Endometrial carcinoma DISXR5CY Definitive Biomarker [2]
Osteosarcoma DISLQ7E2 Definitive Altered Expression [1]
Atrial fibrillation DIS15W6U Strong Biomarker [3]
B-cell neoplasm DISVY326 Strong Genetic Variation [4]
Bladder cancer DISUHNM0 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Altered Expression [8]
Colitis DISAF7DD Strong Biomarker [9]
Endometriosis DISX1AG8 Strong Biomarker [10]
Epithelial neoplasm DIS0T594 Strong Altered Expression [11]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [12]
Fatty liver disease DIS485QZ Strong Genetic Variation [13]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [8]
Liver cancer DISDE4BI Strong Altered Expression [8]
Neoplasm DISZKGEW Strong Biomarker [15]
Ovarian neoplasm DISEAFTY Strong Biomarker [12]
Parkinson disease DISQVHKL Strong Biomarker [16]
Promyelocytic leukaemia DISYGG13 Strong Altered Expression [17]
Stroke DISX6UHX Strong Biomarker [3]
Urinary bladder cancer DISDV4T7 Strong Biomarker [5]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [5]
Alzheimer disease DISF8S70 moderate Altered Expression [18]
Cardiovascular disease DIS2IQDX moderate Biomarker [19]
Chronic obstructive pulmonary disease DISQCIRF moderate Genetic Variation [20]
Endometrial cancer DISW0LMR moderate Biomarker [2]
High blood pressure DISY2OHH moderate Genetic Variation [21]
Hypogonadotropic hypogonadism 7 with or without anosmia DISPBWEU moderate Genetic Variation [22]
Lung carcinoma DISTR26C moderate Biomarker [23]
Ovarian cancer DISZJHAP moderate Biomarker [24]
Prostate cancer DISF190Y moderate Biomarker [25]
Advanced cancer DISAT1Z9 Limited Altered Expression [26]
Asthma DISW9QNS Limited Biomarker [27]
Campomelic dysplasia DISVTW53 Limited Genetic Variation [28]
Castration-resistant prostate carcinoma DISVGAE6 Limited Biomarker [29]
Cholangiocarcinoma DIS71F6X Limited Altered Expression [8]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [30]
Heparin-induced thrombocytopenia DISAKJKZ Limited Biomarker [31]
Intellectual disability DISMBNXP Limited Genetic Variation [32]
Lung cancer DISCM4YA Limited Biomarker [33]
Melanoma DIS1RRCY Limited Biomarker [34]
Nervous system disease DISJ7GGT Limited Genetic Variation [32]
Prostate carcinoma DISMJPLE Limited Biomarker [25]
Renal cell carcinoma DISQZ2X8 Limited Altered Expression [30]
Schizophrenia DISSRV2N Limited Genetic Variation [32]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Steroid receptor RNA activator 1 (SRA1). [35]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Steroid receptor RNA activator 1 (SRA1). [36]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Steroid receptor RNA activator 1 (SRA1). [37]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Steroid receptor RNA activator 1 (SRA1). [38]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Steroid receptor RNA activator 1 (SRA1). [39]
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References

1 LncRNA-SRA1 Suppresses Osteosarcoma Cell Proliferation While Promoting Cell Apoptosis.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819841438. doi: 10.1177/1533033819841438.
2 MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer.J Cancer. 2019 Jan 1;10(2):547-555. doi: 10.7150/jca.27748. eCollection 2019.
3 Refinement of detecting atrial fibrillation in stroke patients: results from the TRACK-AF Study.Eur J Neurol. 2018 Apr;25(4):631-636. doi: 10.1111/ene.13538. Epub 2018 Feb 13.
4 Silencing Nogo-B receptor inhibits penile corpus cavernosum vascular smooth muscle cell apoptosis of rats with diabetic erectile dysfunction by down-regulating ICAM-1.PLoS One. 2019 Aug 23;14(8):e0220715. doi: 10.1371/journal.pone.0220715. eCollection 2019.
5 Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer cells through coactivation of hypoxia inducible factor 1.J Biol Chem. 2014 Apr 18;289(16):11219-11229. doi: 10.1074/jbc.M113.535989. Epub 2014 Feb 28.
6 Drug-induced PD-L1 expression and cell stress response in breast cancer cells can be balanced by drug combination.Sci Rep. 2019 Oct 22;9(1):15099. doi: 10.1038/s41598-019-51537-7.
7 Steroid receptor RNA activator protein (SRAP) expression as a prognostic factor in ER+ human breast tumors.J Cancer Res Clin Oncol. 2013 Oct;139(10):1637-47. doi: 10.1007/s00432-013-1485-2. Epub 2013 Aug 2.
8 Imbalanced expression pattern of steroid receptor coactivator-1 and -3 in liver cancer compared with normal liver: An immunohistochemical study with tissue microarray.Oncol Lett. 2018 Nov;16(5):6339-6348. doi: 10.3892/ol.2018.9443. Epub 2018 Sep 17.
9 SRC-3 protects intestine from DSS-induced colitis by inhibiting inflammation and promoting goblet cell differentiation through enhancement of KLF4 expression.Int J Biol Sci. 2018 Nov 3;14(14):2051-2064. doi: 10.7150/ijbs.28576. eCollection 2018.
10 Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis.J Endocrinol. 2018 Jun;237(3):255-269. doi: 10.1530/JOE-17-0700. Epub 2018 Apr 10.
11 Tyrosine phosphorylation of the nuclear receptor coactivator AIB1/SRC-3 is enhanced by Abl kinase and is required for its activity in cancer cells.Mol Cell Biol. 2008 Nov;28(21):6580-93. doi: 10.1128/MCB.00118-08. Epub 2008 Sep 2.
12 Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer.Biochem Biophys Res Commun. 2006 Jun 2;344(2):667-74. doi: 10.1016/j.bbrc.2006.03.184. Epub 2006 Apr 7.
13 Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis.J Hepatol. 2011 Aug;55(2):445-52. doi: 10.1016/j.jhep.2010.11.022. Epub 2010 Dec 22.
14 Steroid receptor coactivator 3 inhibits hepatitis B virus gene expression through activating Akt signaling to prevent HNF4 nuclear translocation.Cell Biosci. 2019 Aug 13;9:64. doi: 10.1186/s13578-019-0328-5. eCollection 2019.
15 SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer.PLoS Genet. 2017 Mar 8;13(3):e1006650. doi: 10.1371/journal.pgen.1006650. eCollection 2017 Mar.
16 The Neuroprotective Effect of Steroid Receptor Coactivator-Interacting Protein (SIP) in Astrocyte Model of 1-Methyl-4-Phenylpyridinium (MPP?-Induced Parkinson's Disease.Med Sci Monit. 2019 Aug 3;25:5776-5784. doi: 10.12659/MSM.912106.
17 Effect of bleomycin and cisplatin on the expression profile of SRA1, a novel member of pre-mRNA splicing factors, in HL-60 human promyelocytic leukemia cells.Biol Chem. 2007 Aug;388(8):773-8. doi: 10.1515/BC.2007.078.
18 Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence. Cancer Res. 2004 Oct 1;64(19):7156-68. doi: 10.1158/0008-5472.CAN-04-1121.
19 Downregulation of lncRNA-SRA participates in the development of cardiovascular disease in type II diabetic patients.Exp Ther Med. 2019 May;17(5):3367-3372. doi: 10.3892/etm.2019.7362. Epub 2019 Mar 7.
20 Genetic variations in scavenger and ?adrenergic receptors and risk of pulmonary disease.Dan Med J. 2014 Sep;61(9):B4910.
21 Kidney CLC-K chloride channels inhibitors: structure-based studies and efficacy in hypertension and associated CLC-K polymorphisms.J Hypertens. 2016 May;34(5):981-92. doi: 10.1097/HJH.0000000000000876.
22 Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1.J Clin Res Pediatr Endocrinol. 2016 Jun 5;8(2):125-34. doi: 10.4274/jcrpe.3248. Epub 2016 Apr 18.
23 MicroRNA-144-3p suppressed TGF-1-induced lung cancer cell invasion and adhesion by regulating the Src-Akt-Erk pathway.Cell Biol Int. 2020 Jan;44(1):51-61. doi: 10.1002/cbin.11158. Epub 2019 May 18.
24 -Estradiol-dependent activation of the JAK/STAT pathway requires p/CIP and CARM1.Biochim Biophys Acta. 2013 Jun;1833(6):1463-75. doi: 10.1016/j.bbamcr.2013.02.009. Epub 2013 Feb 20.
25 Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer.Clin Cancer Res. 2016 Apr 1;22(7):1744-56. doi: 10.1158/1078-0432.CCR-15-1606. Epub 2015 Nov 9.
26 LncRNA SRA1 is down-regulated in HPV-negative cervical squamous cell carcinoma and regulates cancer cell behaviors.Biosci Rep. 2019 Aug 15;39(8):BSR20191226. doi: 10.1042/BSR20191226. Print 2019 Aug 30.
27 Exhaled breath temperature in optimally treated asthmatics: severity and underlying mechanisms.J Breath Res. 2018 Feb 20;12(2):026013. doi: 10.1088/1752-7163/aa9d46.
28 Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9.Hum Genet. 1996 Feb;97(2):186-93. doi: 10.1007/BF02265263.
29 The steroid receptor coactivator-3 is required for the development of castration-resistant prostate cancer.Cancer Res. 2013 Jul 1;73(13):3997-4008. doi: 10.1158/0008-5472.CAN-12-3929. Epub 2013 May 6.
30 Silencing of lysyl oxidaselike 2 inhibits the migration, invasion and epithelialtomesenchymal transition of renal cell carcinoma cells through the Src/FAK signaling pathway.Int J Oncol. 2019 May;54(5):1676-1690. doi: 10.3892/ijo.2019.4726. Epub 2019 Feb 27.
31 HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.Pathology. 2018 Jun;50(4):426-436. doi: 10.1016/j.pathol.2017.11.089. Epub 2018 Apr 17.
32 CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation.Neuron. 2013 Sep 18;79(6):1169-82. doi: 10.1016/j.neuron.2013.06.039.
33 SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma.Cancer Lett. 2019 Feb 1;442:310-319. doi: 10.1016/j.canlet.2018.11.012. Epub 2018 Nov 10.
34 The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region.Cell Rep. 2016 May 31;15(9):2025-37. doi: 10.1016/j.celrep.2016.04.018. Epub 2016 May 19.
35 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
36 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.
37 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
38 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.
39 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.