Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHTGA1H)

DOT Name Profilin-1 (PFN1)
Synonyms Epididymis tissue protein Li 184a; Profilin I
Gene Name PFN1
Related Disease
Amyotrophic lateral sclerosis type 18 ( )
Esophageal squamous cell carcinoma ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Acute myocardial infarction ( )
Adult glioblastoma ( )
Attention deficit hyperactivity disorder ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cardiac failure ( )
Chronic kidney disease ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Dementia ( )
Depression ( )
Frontotemporal dementia ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
High blood pressure ( )
Keloid ( )
Lung adenocarcinoma ( )
Matthew-Wood syndrome ( )
Myocardial infarction ( )
Neoplasm ( )
Osteoporosis ( )
Ovarian neoplasm ( )
Pick disease ( )
Renal cell carcinoma ( )
Stomach cancer ( )
Triple negative breast cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Familial amyotrophic lateral sclerosis ( )
Hepatocellular carcinoma ( )
Metastatic malignant neoplasm ( )
Plasma cell myeloma ( )
Amyotrophic lateral sclerosis ( )
Wilms tumor ( )
Adenocarcinoma ( )
Advanced cancer ( )
Squamous cell carcinoma ( )
Stroke ( )
UniProt ID
PROF1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1AWI; 1CF0; 1CJF; 1FIK; 1FIL; 1PFL; 2PAV; 2PBD; 3CHW; 4X1L; 4X1M; 4X25; 6NAS; 6NBE; 6NBW; 7P1H; 8BJH; 8BJI; 8BJJ; 8BR0
Pfam ID
PF00235
Sequence
MAGWNAYIDNLMADGTCQDAAIVGYKDSPSVWAAVPGKTFVNITPAEVGVLVGKDRSSFY
VNGLTLGGQKCSVIRDSLLQDGEFSMDLRTKSTGGAPTFNVTVTKTDKTLVLLMGKEGVH
GGLINKKCYEMASHLRRSQY
Function
Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.
Tissue Specificity Expressed in epididymis (at protein level).
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
Regulation of actin cytoskeleton (hsa04810 )
Amyotrophic lateral sclerosis (hsa05014 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Reactome Pathway
Signaling by ROBO receptors (R-HSA-376176 )
PCP/CE pathway (R-HSA-4086400 )
RHO GTPases Activate Formins (R-HSA-5663220 )
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amyotrophic lateral sclerosis type 18 DISPC5KJ Definitive Autosomal dominant [1]
Esophageal squamous cell carcinoma DIS5N2GV Definitive Biomarker [2]
Pancreatic cancer DISJC981 Definitive Biomarker [3]
Prostate cancer DISF190Y Definitive Altered Expression [4]
Prostate carcinoma DISMJPLE Definitive Altered Expression [4]
Acute myocardial infarction DISE3HTG Strong Altered Expression [5]
Adult glioblastoma DISVP4LU Strong Posttranslational Modification [6]
Attention deficit hyperactivity disorder DISL8MX9 Strong Biomarker [7]
Bladder cancer DISUHNM0 Strong Altered Expression [8]
Breast cancer DIS7DPX1 Strong Biomarker [9]
Breast carcinoma DIS2UE88 Strong Biomarker [9]
Breast neoplasm DISNGJLM Strong Altered Expression [10]
Cardiac failure DISDC067 Strong Biomarker [11]
Chronic kidney disease DISW82R7 Strong Altered Expression [12]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [13]
Congestive heart failure DIS32MEA Strong Biomarker [11]
Dementia DISXL1WY Strong Genetic Variation [14]
Depression DIS3XJ69 Strong Biomarker [15]
Frontotemporal dementia DISKYHXL Strong Genetic Variation [16]
Gastric cancer DISXGOUK Strong Altered Expression [17]
Glioblastoma multiforme DISK8246 Strong Posttranslational Modification [6]
Glioma DIS5RPEH Strong Posttranslational Modification [6]
High blood pressure DISY2OHH Strong Biomarker [18]
Keloid DISV09JY Strong Biomarker [19]
Lung adenocarcinoma DISD51WR Strong Altered Expression [20]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [3]
Myocardial infarction DIS655KI Strong Altered Expression [5]
Neoplasm DISZKGEW Strong Biomarker [21]
Osteoporosis DISF2JE0 Strong Biomarker [22]
Ovarian neoplasm DISEAFTY Strong Altered Expression [23]
Pick disease DISP6X50 Strong Genetic Variation [24]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [25]
Stomach cancer DISKIJSX Strong Altered Expression [17]
Triple negative breast cancer DISAMG6N Strong Altered Expression [26]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [8]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [8]
Familial amyotrophic lateral sclerosis DISWZ9CJ moderate Genetic Variation [27]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [21]
Metastatic malignant neoplasm DIS86UK6 moderate Biomarker [28]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [29]
Amyotrophic lateral sclerosis DISF7HVM Supportive Autosomal dominant [30]
Wilms tumor DISB6T16 Disputed Biomarker [31]
Adenocarcinoma DIS3IHTY Limited Altered Expression [32]
Advanced cancer DISAT1Z9 Limited Biomarker [33]
Squamous cell carcinoma DISQVIFL Limited Biomarker [34]
Stroke DISX6UHX Limited Biomarker [35]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
22 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 Profilin-1 (PFN1). [36]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Profilin-1 (PFN1). [37]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Profilin-1 (PFN1). [38]
Quercetin DM3NC4M Approved Quercetin increases the expression of Profilin-1 (PFN1). [39]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Profilin-1 (PFN1). [40]
Selenium DM25CGV Approved Selenium increases the expression of Profilin-1 (PFN1). [41]
Aspirin DM672AH Approved Aspirin decreases the expression of Profilin-1 (PFN1). [42]
DTI-015 DMXZRW0 Approved DTI-015 decreases the expression of Profilin-1 (PFN1). [43]
Malathion DMXZ84M Approved Malathion decreases the expression of Profilin-1 (PFN1). [44]
Azacitidine DMTA5OE Approved Azacitidine increases the expression of Profilin-1 (PFN1). [45]
Cocaine DMSOX7I Approved Cocaine increases the expression of Profilin-1 (PFN1). [46]
Benzatropine DMF7EXL Approved Benzatropine increases the expression of Profilin-1 (PFN1). [47]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of Profilin-1 (PFN1). [48]
Haloperidol DM96SE0 Approved Haloperidol increases the expression of Profilin-1 (PFN1). [47]
Etretinate DM2CZFA Approved Etretinate decreases the expression of Profilin-1 (PFN1). [50]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Profilin-1 (PFN1). [51]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Profilin-1 (PFN1). [41]
Tanespimycin DMNLQHK Phase 2 Tanespimycin increases the expression of Profilin-1 (PFN1). [52]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Profilin-1 (PFN1). [53]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Profilin-1 (PFN1). [55]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Profilin-1 (PFN1). [56]
AHPN DM8G6O4 Investigative AHPN decreases the expression of Profilin-1 (PFN1). [57]
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⏷ Show the Full List of 22 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Dihydroartemisinin DMBXVMZ Approved Dihydroartemisinin affects the binding of Profilin-1 (PFN1). [49]
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1 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 Profilin-1 (PFN1). [54]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Using proteomic approach to identify tumor-associated proteins as biomarkers in human esophageal squamous cell carcinoma.J Proteome Res. 2011 Jun 3;10(6):2863-72. doi: 10.1021/pr200141c. Epub 2011 May 3.
3 Profilin-1 suppresses tumorigenicity in pancreatic cancer through regulation of the SIRT3-HIF1 axis.Mol Cancer. 2014 Aug 7;13:187. doi: 10.1186/1476-4598-13-187.
4 Cathepsin X Cleaves Profilin 1 C-Terminal Tyr139 and Influences Clathrin-Mediated Endocytosis.PLoS One. 2015 Sep 1;10(9):e0137217. doi: 10.1371/journal.pone.0137217. eCollection 2015.
5 Expression of profilin-1 in endothelial cells of rats with acute myocardial infarction.Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1318-1322.
6 Profilin-1 phosphorylation directs angiocrine expression and glioblastoma progression throughHIF-1 accumulation.Nat Cell Biol. 2014 May;16(5):445-56. doi: 10.1038/ncb2954. Epub 2014 Apr 20.
7 Psychometric Properties and Factor Structure of the Short Form of the Affective Lability Scale in Adult Patients With ADHD.J Atten Disord. 2019 Aug;23(10):1079-1089. doi: 10.1177/1087054717690808. Epub 2017 Feb 2.
8 Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models.Oncotarget. 2016 Oct 25;7(43):70750-70768. doi: 10.18632/oncotarget.12218.
9 Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis.Nutr Cancer. 2019;71(8):1263-1271. doi: 10.1080/01635581.2019.1607407. Epub 2019 May 14.
10 Profilin-1 deficiency leads to SMAD3 upregulation and impaired 3D outgrowth of breast cancer cells.Br J Cancer. 2018 Oct;119(9):1106-1117. doi: 10.1038/s41416-018-0284-6. Epub 2018 Oct 15.
11 Profilin? contributes to cardiac injury induced by advanced glycation endproducts in rats.Mol Med Rep. 2017 Nov;16(5):6634-6641. doi: 10.3892/mmr.2017.7446. Epub 2017 Sep 8.
12 The association of profilin-1 levels with survival in chronic kidney disease.Eur J Clin Invest. 2017 Dec;47(12). doi: 10.1111/eci.12839. Epub 2017 Oct 27.
13 Identification of profilin 1 as the primary target for the anti-cancer activities of Furowanin A in colorectal cancer.Pharmacol Rep. 2019 Oct;71(5):940-949. doi: 10.1016/j.pharep.2019.05.007. Epub 2019 May 30.
14 A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts.Neurobiol Aging. 2013 Jun;34(6):1708.e1-6. doi: 10.1016/j.neurobiolaging.2012.10.009. Epub 2012 Nov 8.
15 Assessment of Affect Lability: Psychometric Properties of the ALS-18.Front Psychol. 2018 Mar 29;9:427. doi: 10.3389/fpsyg.2018.00427. eCollection 2018.
16 Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.J Neurol Neurosurg Psychiatry. 2014 May;85(5):506-8. doi: 10.1136/jnnp-2013-306761. Epub 2013 Dec 5.
17 Silencing profilin-1 inhibits gastric cancer progression via integrin 1/focal adhesion kinase pathway modulation.World J Gastroenterol. 2015 Feb 28;21(8):2323-35. doi: 10.3748/wjg.v21.i8.2323.
18 Mechanism of action of Profilin-1 and Fibulin-3 in vascular remodeling in hypertensive rats.Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):8101-8108. doi: 10.26355/eurrev_201909_19028.
19 Comparative proteomic analysis between normal skin and keloid scar.Br J Dermatol. 2010 Jun;162(6):1302-15. doi: 10.1111/j.1365-2133.2010.09660.x. Epub 2010 Feb 1.
20 The effect of piperlongumine on endothelial and lung adenocarcinoma cells with regulated expression of profilin-1.Onco Targets Ther. 2018 Nov 22;11:8275-8292. doi: 10.2147/OTT.S183191. eCollection 2018.
21 Profilin 1, negatively regulated by microRNA-19a-3p, serves as a tumor suppressor in human hepatocellular carcinoma.Pathol Res Pract. 2019 Mar;215(3):499-505. doi: 10.1016/j.prp.2018.12.012. Epub 2018 Dec 12.
22 Comparative proteomics analysis of microvesicles in human serum for the evaluation of osteoporosis.Electrophoresis. 2019 Jul;40(14):1839-1847. doi: 10.1002/elps.201900130. Epub 2019 May 21.
23 BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility - A proteomics study.Cell Cycle. 2015;14(12):1884-92. doi: 10.1080/15384101.2015.1036203.
24 Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia.Neurobiol Aging. 2013 May;34(5):1517.e9-10. doi: 10.1016/j.neurobiolaging.2012.09.016. Epub 2012 Oct 11.
25 Profilin-1 expression is associated with high grade and stage and decreased disease-free survival in renal cell carcinoma.Hum Pathol. 2015 May;46(5):673-80. doi: 10.1016/j.humpath.2014.11.007. Epub 2014 Nov 26.
26 Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1.Tumour Biol. 2013 Jun;34(3):1713-22. doi: 10.1007/s13277-013-0708-0. Epub 2013 Feb 22.
27 A Drosophila model of ALS reveals a partial loss of function of causative human PFN1 mutants.Hum Mol Genet. 2017 Jun 1;26(11):2146-2155. doi: 10.1093/hmg/ddx112.
28 Alterative Expression and Localization of Profilin 1/VASPpS157 and Cofilin 1/VASPpS239 Regulates Metastatic Growth and Is Modified by DHA Supplementation.Mol Cancer Ther. 2016 Sep;15(9):2220-31. doi: 10.1158/1535-7163.MCT-16-0092. Epub 2016 Aug 5.
29 Profilin 1 induces drug resistance through Beclin1 complex-mediated autophagy in multiple myeloma.Cancer Sci. 2018 Sep;109(9):2706-2716. doi: 10.1111/cas.13711. Epub 2018 Jul 27.
30 Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23;488(7412):499-503. doi: 10.1038/nature11280.
31 Screening and identification of non-inflammatory specific protein markers in Wilms' tumor tissues.Arch Biochem Biophys. 2019 Nov 15;676:108112. doi: 10.1016/j.abb.2019.108112. Epub 2019 Sep 21.
32 Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation.J Cell Physiol. 2010 Jun;223(3):623-9. doi: 10.1002/jcp.22058.
33 A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells.Cell Cycle. 2017;16(24):2366-2373. doi: 10.1080/15384101.2017.1346759.
34 A loss of profilin-1 in late-stage oral squamous cell carcinoma.J Oral Pathol Med. 2017 Aug;46(7):489-495. doi: 10.1111/jop.12523. Epub 2016 Dec 18.
35 Role of GSPE in improving early cerebral vascular damage by inhibition of Profilin-1 expression in a ouabain-induced hypertension model.Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6999-7012. doi: 10.26355/eurrev_201810_16171.
36 Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
37 Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
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 Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.
40 MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
41 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
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43 Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
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45 The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
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48 Proteomics investigation of protein expression changes in ouabain induced apoptosis in human umbilical vein endothelial cells. J Cell Biochem. 2008 Jun 1;104(3):1054-64. doi: 10.1002/jcb.21691.
49 Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
50 Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics. Toxicol Lett. 2017 Nov 5;281:26-34. doi: 10.1016/j.toxlet.2017.09.001. Epub 2017 Sep 5.
51 Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
52 Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
53 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.
54 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.
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56 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
57 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.