Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW18FQN)

DOT Name Serum response factor (SRF)
Synonyms SRF
Gene Name SRF
Related Disease
Dilated cardiomyopathy 1A ( )
Neoplasm ( )
Acute megakaryoblastic leukemia ( )
Advanced cancer ( )
Alzheimer disease ( )
Benign neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Cardiac failure ( )
Cervical cancer ( )
Cervical carcinoma ( )
Congestive heart failure ( )
Coronary heart disease ( )
Depression ( )
Dilated cardiomyopathy ( )
Epilepsy ( )
Gastric cancer ( )
High blood pressure ( )
HIV infectious disease ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphangioleiomyomatosis ( )
Non-small-cell lung cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Psoriasis ( )
Schizophrenia ( )
Smith-McCort dysplasia 1 ( )
Stomach cancer ( )
Stroke ( )
Systemic sclerosis ( )
Thyroid gland papillary carcinoma ( )
Uterine fibroids ( )
Chronic obstructive pulmonary disease ( )
Lung adenocarcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Hepatocellular carcinoma ( )
Metastatic malignant neoplasm ( )
Pancreatic cancer ( )
Rheumatoid arthritis ( )
Small lymphocytic lymphoma ( )
UniProt ID
SRF_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1HBX; 1K6O; 1SRS
Pfam ID
PF00319
Sequence
MLPTQAGAAAALGRGSALGGSLNRTPTGRPGGGGGTRGANGGRVPGNGAGLGPGRLEREA
AAAAATTPAPTAGALYSGSEGDSESGEEEELGAERRGLKRSLSEMEIGMVVGGPEASAAA
TGGYGPVSGAVSGAKPGKKTRGRVKIKMEFIDNKLRRYTTFSKRKTGIMKKAYELSTLTG
TQVLLLVASETGHVYTFATRKLQPMITSETGKALIQTCLNSPDSPPRSDPTTDQRMSATG
FEETDLTYQVSESDSSGETKDTLKPAFTVTNLPGTTSTIQTAPSTSTTMQVSSGPSFPIT
NYLAPVSASVSPSAVSSANGTVLKSTGSGPVSSGGLMQLPTSFTLMPGGAVAQQVPVQAI
QVHQAPQQASPSRDSSTDLTQTSSSGTVTLPATIMTSSVPTTVGGHMMYPSPHAVMYAPT
SGLGDGSLTVLNAFSQAPSTMQVSHSQVQEPGGVPQVFLTASSGTVQIPVSAVQLHQMAV
IGQQAGSSSNLTELQVVNLDTAHSTKSE
Function
SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. Required for cardiac differentiation and maturation.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
cGMP-PKG sig.ling pathway (hsa04022 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Viral carcinogenesis (hsa05203 )
Reactome Pathway
NGF-stimulated transcription (R-HSA-9031628 )
Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638 )
Cardiogenesis (R-HSA-9733709 )
Regulation of NPAS4 gene transcription (R-HSA-9768777 )
RHO GTPases Activate Formins (R-HSA-5663220 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Dilated cardiomyopathy 1A DIS0RK9Z Definitive Biomarker [1]
Neoplasm DISZKGEW Definitive Genetic Variation [2]
Acute megakaryoblastic leukemia DIS0JX3M Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Altered Expression [5]
Benign neoplasm DISDUXAD Strong Therapeutic [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Carcinoma DISH9F1N Strong Biomarker [8]
Cardiac failure DISDC067 Strong Biomarker [9]
Cervical cancer DISFSHPF Strong Biomarker [10]
Cervical carcinoma DIST4S00 Strong Biomarker [10]
Congestive heart failure DIS32MEA Strong Biomarker [9]
Coronary heart disease DIS5OIP1 Strong Biomarker [11]
Depression DIS3XJ69 Strong Biomarker [12]
Dilated cardiomyopathy DISX608J Strong Biomarker [1]
Epilepsy DISBB28L Strong Biomarker [13]
Gastric cancer DISXGOUK Strong Biomarker [14]
High blood pressure DISY2OHH Strong Biomarker [15]
HIV infectious disease DISO97HC Strong Biomarker [16]
Liver cancer DISDE4BI Strong Biomarker [17]
Lung cancer DISCM4YA Strong Altered Expression [4]
Lung carcinoma DISTR26C Strong Altered Expression [4]
Lymphangioleiomyomatosis DISR0RNB Strong Biomarker [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [19]
Prostate cancer DISF190Y Strong Biomarker [20]
Prostate carcinoma DISMJPLE Strong Biomarker [20]
Prostate neoplasm DISHDKGQ Strong Biomarker [21]
Psoriasis DIS59VMN Strong Biomarker [22]
Schizophrenia DISSRV2N Strong Genetic Variation [23]
Smith-McCort dysplasia 1 DIS8072R Strong Biomarker [11]
Stomach cancer DISKIJSX Strong Biomarker [14]
Stroke DISX6UHX Strong Biomarker [24]
Systemic sclerosis DISF44L6 Strong Biomarker [25]
Thyroid gland papillary carcinoma DIS48YMM Strong Altered Expression [26]
Uterine fibroids DISBZRMJ Strong Genetic Variation [2]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [27]
Lung adenocarcinoma DISD51WR moderate Biomarker [28]
Colon cancer DISVC52G Limited Altered Expression [29]
Colon carcinoma DISJYKUO Limited Altered Expression [29]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [30]
Metastatic malignant neoplasm DIS86UK6 Limited Altered Expression [31]
Pancreatic cancer DISJC981 Limited Biomarker [32]
Rheumatoid arthritis DISTSB4J Limited Altered Expression [33]
Small lymphocytic lymphoma DIS30POX Limited Biomarker [15]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Serum response factor (SRF). [34]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Serum response factor (SRF). [35]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Serum response factor (SRF). [36]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Serum response factor (SRF). [37]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Serum response factor (SRF). [38]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Serum response factor (SRF). [40]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Serum response factor (SRF). [43]
Nitrobenzanthrone DMN6L70 Investigative Nitrobenzanthrone increases the expression of Serum response factor (SRF). [44]
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⏷ Show the Full List of 8 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Serum response factor (SRF). [39]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Serum response factor (SRF). [41]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Serum response factor (SRF). [42]
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References

1 Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset.JCI Insight. 2019 Mar 21;4(6):e124629. doi: 10.1172/jci.insight.124629. eCollection 2019 Mar 21.
2 Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior.Am J Surg Pathol. 2020 Jan;44(1):55-60. doi: 10.1097/PAS.0000000000001336.
3 Involvement of SRF coactivator MKL2 in BDNF-mediated activation of the synaptic activity-responsive element in the Arc gene.J Neurochem. 2019 Jan;148(2):204-218. doi: 10.1111/jnc.14596. Epub 2018 Nov 12.
4 IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner.Nucleic Acids Res. 2019 Jan 10;47(1):375-390. doi: 10.1093/nar/gky1012.
5 Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype.Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):823-8. doi: 10.1073/pnas.0608251104. Epub 2007 Jan 10.
6 Cellular toxicity induced by SRF-mediated transcriptional squelching.Toxicol Sci. 2007 Mar;96(1):83-91. doi: 10.1093/toxsci/kfl172. Epub 2006 Nov 20.
7 miR-206 Inhibits Stemness and Metastasis of Breast Cancer by Targeting MKL1/IL11 Pathway.Clin Cancer Res. 2017 Feb 15;23(4):1091-1103. doi: 10.1158/1078-0432.CCR-16-0943. Epub 2016 Jul 19.
8 Expression of serum response factor in gastric carcinoma and its molecular mechanisms involved in the regulation of the invasion and migration of SGC-7901 cells.Cancer Biother Radiopharm. 2013 Mar;28(2):146-52. doi: 10.1089/cbr.2012.1265. Epub 2012 Nov 7.
9 Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction.Dis Model Mech. 2012 Jul;5(4):481-91. doi: 10.1242/dmm.009456. Epub 2012 Apr 5.
10 Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr? and epithelial-mesenchymal transition.Int J Mol Med. 2019 Jan;43(1):614-620. doi: 10.3892/ijmm.2018.3954. Epub 2018 Oct 24.
11 Coronary Disease-Associated Gene TCF21 Inhibits Smooth Muscle Cell Differentiation by Blocking the Myocardin-Serum Response Factor Pathway.Circ Res. 2020 Feb 14;126(4):517-529. doi: 10.1161/CIRCRESAHA.119.315968. Epub 2019 Dec 9.
12 The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex.J Neurosci. 2017 Jul 12;37(28):6628-6637. doi: 10.1523/JNEUROSCI.0766-17.2017. Epub 2017 Jun 12.
13 Epilepsy Associates with Decreased HIF-1/STAT5b Signaling in Glioblastoma.Cancers (Basel). 2019 Jan 4;11(1):41. doi: 10.3390/cancers11010041.
14 Overexpression of serum response factor is correlated with poor prognosis in patients with gastric cancer.Hum Pathol. 2019 Mar;85:10-17. doi: 10.1016/j.humpath.2018.10.018. Epub 2018 Nov 27.
15 Upregulation of SRF Is Associated With Hypoxic Pulmonary Hypertension by Promoting Viability of Smooth Muscle Cells via Increasing Expression of Bcl-2.J Cell Biochem. 2017 Sep;118(9):2731-2738. doi: 10.1002/jcb.25922. Epub 2017 Apr 25.
16 Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
17 Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat.Cancer Lett. 1997 Nov 11;119(2):137-41. doi: 10.1016/s0304-3835(97)00263-2.
18 Imbalanced plasminogen system in lymphangioleiomyomatosis: potential role of serum response factor.Am J Respir Cell Mol Biol. 2005 Jan;32(1):28-34. doi: 10.1165/rcmb.2004-0289OC. Epub 2004 Oct 28.
19 Small interfering RNA-mediated suppression of serum response factor, E2-promotor binding factor and survivin in non-small cell lung cancer cell lines by non-viral transfection.Eur J Cardiothorac Surg. 2013 Mar;43(3):628-33; discussion 633-4. doi: 10.1093/ejcts/ezs337. Epub 2012 Nov 14.
20 Protein Kinase N1 control of androgen-responsive serum response factor action provides rationale for novel prostate cancer treatment strategy.Oncogene. 2019 Jun;38(23):4496-4511. doi: 10.1038/s41388-019-0732-7. Epub 2019 Feb 11.
21 Identification of transcription factors associated with castration-resistance: is the serum responsive factor a potential therapeutic target?.Prostate. 2013 May;73(7):743-53. doi: 10.1002/pros.22618. Epub 2013 Jan 28.
22 Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice.J Clin Invest. 2009 Apr;119(4):899-910. doi: 10.1172/JCI37771. Epub 2009 Mar 23.
23 Loss of serum response factor in mature neurons in the dentate gyrus alters the morphology of dendritic spines and hippocampus-dependent behavioral tasks.Brain Struct Funct. 2019 Nov;224(8):2691-2701. doi: 10.1007/s00429-019-01925-6. Epub 2019 Aug 2.
24 Characterization of a novel murine model for spontaneous hemorrhagic stroke using in vivo PET and MR multiparametric imaging.Neuroimage. 2017 Jul 15;155:245-256. doi: 10.1016/j.neuroimage.2017.04.071. Epub 2017 May 1.
25 5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma.J Med Chem. 2019 May 9;62(9):4350-4369. doi: 10.1021/acs.jmedchem.8b01772. Epub 2019 Apr 18.
26 The expression and role of serum response factor in papillary carcinoma of the thyroid.Int J Oncol. 2009 Jul;35(1):49-55.
27 Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD.Int J Chron Obstruct Pulmon Dis. 2017 Feb 20;12:581-587. doi: 10.2147/COPD.S109243. eCollection 2017.
28 Genome-wide investigation of the clinical significance and prospective molecular mechanism of minichromosome maintenance protein family genes in patients with Lung Adenocarcinoma.PLoS One. 2019 Jul 19;14(7):e0219467. doi: 10.1371/journal.pone.0219467. eCollection 2019.
29 Serum response factor is alternatively spliced in human colon cancer.J Surg Res. 2004 Sep;121(1):92-100. doi: 10.1016/j.jss.2004.02.031.
30 Inhibition of TRPM7 blocks MRTF/SRF-dependent transcriptional and tumorigenic activity.Oncogene. 2020 Mar;39(11):2328-2344. doi: 10.1038/s41388-019-1140-8. Epub 2019 Dec 16.
31 Tumor Progression Is Mediated by Thymosin-4 through a TGF/MRTF Signaling Axis.Mol Cancer Res. 2018 May;16(5):880-893. doi: 10.1158/1541-7786.MCR-17-0715. Epub 2018 Jan 12.
32 The MRTF-A/B function as oncogenes in pancreatic cancer.Oncol Rep. 2016 Jan;35(1):127-38. doi: 10.3892/or.2015.4329. Epub 2015 Oct 15.
33 Serum response elements activate and cAMP responsive elements inhibit expression of transcription factor Egr-1 in synovial fibroblasts of rheumatoid arthritis patients.Int Immunol. 1999 Jan;11(1):47-61. doi: 10.1093/intimm/11.1.47.
34 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.
35 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
36 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.
37 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
38 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
39 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
40 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
41 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.
42 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
43 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
44 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.