Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5SSSA7)

• DOT Name: Profilin-2 (PFN2)
• Synonyms: Profilin II
• Gene Name: PFN2
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Acute megakaryoblastic leukemia
  Anemia
  Breast cancer
  Breast carcinoma
  Charcot marie tooth disease
  Colorectal carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Head-neck squamous cell carcinoma
  Squamous cell carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Advanced cancer
  Amyotrophic lateral sclerosis
  Myocardial infarction
• UniProt ID: PROF2_HUMAN
• PDB ID: 1D1J
• Pfam ID: PF00235
• Sequence:
  MAGWQSYVDNLMCDGCCQEAAIVGYCDAKYVWAATAGGVFQSITPIEIDMIVGKDREGFF
  TNGLTLGAKKCSVIRDSLYVDGDCTMDIRTKSQGGEPTYNVAVGRAGRVLVFVMGKEGVH
  GGGLNKKAYSMAKYLRDSGF
• 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.
• Tissue Specificity: Highly expressed in brain, skeletal muscle and kidney and less strongly in heart, placenta, lung and liver.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Regulation of actin cytoskeleton (hsa04810)
  Amyotrophic lateral sclerosis (hsa05014)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  RHO GTPases Activate Formins (R-HSA-5663220)
  Signaling by ROBO receptors (R-HSA-376176)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[2]
Anemia	DISTVL0C	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Charcot marie tooth disease	DIS3BT2L	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[7]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[8]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[9]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Disputed	Genetic Variation	[10]
Ovarian cancer	DISZJHAP	Disputed	Genetic Variation	[10]
Ovarian neoplasm	DISEAFTY	Disputed	Genetic Variation	[10]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[7]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[11]
Myocardial infarction	DIS655KI	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Profilin-2 (PFN2).	[13]

8 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 Profilin-2 (PFN2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Profilin-2 (PFN2).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Profilin-2 (PFN2).	[16]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Profilin-2 (PFN2).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Profilin-2 (PFN2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Profilin-2 (PFN2).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Profilin-2 (PFN2).	[20]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Profilin-2 (PFN2).	[21]

References

• [1] Long non-coding RNA TUG1 regulates the progression and metastasis of osteosarcoma cells via miR-140-5p/PFN2 axis.Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):9781-9792. doi: 10.26355/eurrev_201911_19541.
• [2] The myocardin-related transcription factor MKL co-regulates the cellular levels of two profilin isoforms.J Biol Chem. 2017 Jul 14;292(28):11777-11791. doi: 10.1074/jbc.M117.781104. Epub 2017 May 25.
• [3] The actin-binding protein profilin 2 is a novel regulator of iron homeostasis.Blood. 2017 Oct 26;130(17):1934-1945. doi: 10.1182/blood-2016-11-754382. Epub 2017 Aug 3.
• [4] Long noncoding RNA FOXD2AS1/miR?50?p/PFN2 axis regulates breast cancer malignancy and tumorigenesis.Int J Oncol. 2019 Mar;54(3):1043-1052. doi: 10.3892/ijo.2019.4671. Epub 2019 Jan 3.
• [5] PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease.J Neurol Neurosurg Psychiatry. 2018 Aug;89(8):870-878. doi: 10.1136/jnnp-2017-317562. Epub 2018 Feb 15.
• [6] Loss of profilin2 contributes to enhanced epithelial-mesenchymal transition and metastasis of colorectal cancer.Int J Oncol. 2018 Sep;53(3):1118-1128. doi: 10.3892/ijo.2018.4475. Epub 2018 Jul 9.
• [7] Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/-Catenin Signaling Pathway.Oncol Res. 2019 Sep 23;27(9):1079-1088. doi: 10.3727/096504019X15579146061957. Epub 2019 May 15.
• [8] MicroRNA-30a-5p suppresses epithelial-mesenchymal transition by targeting profilin-2 in high invasive non-small cell lung cancer cell lines.Oncol Rep. 2017 May;37(5):3146-3154. doi: 10.3892/or.2017.5566. Epub 2017 Apr 11.
• [9] Bioinformatic analysis of PFN2 dysregulation and its prognostic value in head and neck squamous carcinoma.Future Oncol. 2018 Feb;14(5):449-459. doi: 10.2217/fon-2017-0348. Epub 2018 Jan 11.
• [10] FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway.Cell Death Dis. 2014 Jul 17;5(7):e1346. doi: 10.1038/cddis.2014.302.
• [11] Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics.J Neurosci. 2014 Jun 11;34(24):8083-97. doi: 10.1523/JNEUROSCI.0543-14.2014.
• [12] Knocking down PFL can improve myocardial ischemia/reperfusion injury in rats by up-regulating heat shock protein-20.Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7619-7627. doi: 10.26355/eurrev_201909_18885.
• [13] 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.
• [14] 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.
• [15] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [16] 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.
• [17] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Alteration of estrogen-regulated gene expression in human cells induced by the agricultural and horticultural herbicide glyphosate. Hum Exp Toxicol. 2007 Sep;26(9):747-52. doi: 10.1177/0960327107083453.