Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-parvin (PARVA)
• Synonyms: Actopaxin; CH-ILKBP; Calponin-like integrin-linked kinase-binding protein; Matrix-remodeling-associated protein 2
• Gene Name: PARVA
• Related Disease:
  Melanoma
  Drug dependence
  Substance abuse
  Substance dependence
  Breast cancer
  Breast carcinoma
  Triple negative breast cancer
• UniProt ID: PARVA_HUMAN
• PDB ID: 2K2R; 2VZC; 2VZD; 2VZG; 2VZI; 3KMU; 3KMW; 3REP; 6MIB
• Pfam ID: PF00307
• Sequence:
  MATSPQKSPSVPKSPTPKSPPSRKKDDSFLGKLGGTLARRKKAKEVSELQEEGMNAINLP
  LSPIPFELDPEDTMLEENEVRTMVDPNSRSDPKLQELMKVLIDWINDVLVGERIIVKDLA
  EDLYDGQVLQKLFEKLESEKLNVAEVTQSEIAQKQKLQTVLEKINETLKLPPRSIKWNVD
  SVHAKSLVAILHLLVALSQYFRAPIRLPDHVSIQVVVVQKREGILQSRQIQEEITGNTEA
  LSGRHERDAFDTLFDHAPDKLNVVKKTLITFVNKHLNKLNLEVTELETQFADGVYLVLLM
  GLLEGYFVPLHSFFLTPDSFEQKVLNVSFAFELMQDGGLEKPKPRPEDIVNCDLKSTLRV
  LYNLFTKYRNVE
• Function: Plays a role in sarcomere organization and in smooth muscle cell contraction. Required for normal development of the embryonic cardiovascular system, and for normal septation of the heart outflow tract. Plays a role in sprouting angiogenesis and is required for normal adhesion of vascular smooth muscle cells to endothelial cells during blood vessel development. Plays a role in the reorganization of the actin cytoskeleton, formation of lamellipodia and ciliogenesis. Plays a role in the establishment of cell polarity, cell adhesion, cell spreading, and directed cell migration.
• Tissue Specificity: Widely expressed, with highest levels in heart, skeletal muscle, kidney and liver.
• KEGG Pathway: Focal adhesion (hsa04510)
• Reactome Pathway:
  Cell-extracellular matrix interactions (R-HSA-446353)
  Regulation of cytoskeletal remodeling and cell spreading by IPP complex components (R-HSA-446388)
  Localization of the PINCH-ILK-PARVIN complex to focal adhesions (R-HSA-446343)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Drug dependence	DIS9IXRC	Strong	Biomarker	[2]
Substance abuse	DIS327VW	Strong	Biomarker	[2]
Substance dependence	DISDRAAR	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Limited	Biomarker	[3]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Limited	Altered Expression	[3]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Alpha-parvin (PARVA).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alpha-parvin (PARVA).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Alpha-parvin (PARVA).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Alpha-parvin (PARVA).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-parvin (PARVA).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Alpha-parvin (PARVA).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Alpha-parvin (PARVA).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Alpha-parvin (PARVA).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Alpha-parvin (PARVA).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Alpha-parvin (PARVA).	[7]

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 affects the methylation of Alpha-parvin (PARVA).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Alpha-parvin (PARVA).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Alpha-parvin (PARVA).	[15]

References

• [1] A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression.Nat Commun. 2018 Jan 31;9(1):461. doi: 10.1038/s41467-018-02851-7.
• [2] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [3] -Parvin promotes breast cancer progression and metastasis through interaction with G3BP2 and regulation of TWIST1 signaling.Oncogene. 2019 Jun;38(24):4856-4874. doi: 10.1038/s41388-019-0762-1. Epub 2019 Feb 25.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.