Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9OGVWX)

• DOT Name: Beta-parvin (PARVB)
• Synonyms: Affixin
• Gene Name: PARVB
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Autosomal recessive limb-girdle muscular dystrophy type 2B
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Intracerebral hemorrhage
  Neoplasm
  Non-alcoholic fatty liver disease
  Megalencephaly
• UniProt ID: PARVB_HUMAN
• PDB ID: 4EDL; 4EDM; 4EDN
• Pfam ID: PF00307
• Sequence:
  MSSAPRSPTPRPRRMKKDESFLGKLGGTLARKRRAREVSDLQEEGKNAINSPMSPALVDV
  HPEDTQLEENEERTMIDPTSKEDPKFKELVKVLLDWINDVLVEERIIVKQLEEDLYDGQV
  LQKLLEKLAGCKLNVAEVTQSEIGQKQKLQTVLEAVHDLLRPRGWALRWSVDSIHGKNLV
  AILHLLVSLAMHFRAPIRLPEHVTVQVVVVRKREGLLHSSHISEELTTTTEMMMGRFERD
  AFDTLFDHAPDKLSVVKKSLITFVNKHLNKLNLEVTELETQFADGVYLVLLMGLLEDYFV
  PLHHFYLTPESFDQKVHNVSFAFELMLDGGLKKPKARPEDVVNLDLKSTLRVLYNLFTKY
  KNVE
• Function: Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration.
• Tissue Specificity: Expressed predominantly in heart and skeletal muscle.
• KEGG Pathway: Focal adhesion (hsa04510)
• Reactome Pathway:
  Regulation of cytoskeletal remodeling and cell spreading by IPP complex components (R-HSA-446388)
  Cell-extracellular matrix interactions (R-HSA-446353)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Autosomal recessive limb-girdle muscular dystrophy type 2B	DISWWCL7	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Intracerebral hemorrhage	DISC81BT	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[9]
Megalencephaly	DISYW5SV	Limited	Genetic Variation	[10]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Lovastatin	DM9OZWQ	Approved	Beta-parvin (PARVB) decreases the response to substance of Lovastatin.	[17]
Bevacizumab	DMSD1UN	Approved	Beta-parvin (PARVB) increases the Hypertension ADR of Bevacizumab.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Beta-parvin (PARVB).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Beta-parvin (PARVB).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Beta-parvin (PARVB).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Beta-parvin (PARVB).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Beta-parvin (PARVB).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Beta-parvin (PARVB).	[16]

References

• [1] Differential expressions of integrin-linked kinase, -parvin and cofilin 1 in high-fat diet induced prostate cancer progression in a transgenic mouse model.Oncol Lett. 2018 Oct;16(4):4945-4952. doi: 10.3892/ol.2018.9276. Epub 2018 Aug 7.
• [2] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [3] Dysferlin interacts with affixin (beta-parvin) at the sarcolemma.J Neuropathol Exp Neurol. 2005 Apr;64(4):334-40. doi: 10.1093/jnen/64.4.334.
• [4] Parvin-beta inhibits breast cancer tumorigenicity and promotes CDK9-mediated peroxisome proliferator-activated receptor gamma 1 phosphorylation.Mol Cell Biol. 2008 Jan;28(2):687-704. doi: 10.1128/MCB.01617-06. Epub 2007 Nov 12.
• [5] Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer. 2014 Sep 9;111(6):1241-8. doi: 10.1038/bjc.2014.430. Epub 2014 Aug 12.
• [6] Focal Adhesion Proteins - and -Parvin are Overexpressed in Human Colorectal Cancer and Correlate with Tumor Progression.Cancer Invest. 2015;33(8):387-97. doi: 10.3109/07357907.2015.1047508. Epub 2015 Jun 26.
• [7] 17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage.Stroke. 2018 Jul;49(7):1618-1625. doi: 10.1161/STROKEAHA.117.020091. Epub 2018 Jun 18.
• [8] PARVB overexpression increases cell migration capability and defines high risk for endophytic growth and metastasis in tongue squamous cell carcinoma.Br J Cancer. 2015 Jan 20;112(2):338-44. doi: 10.1038/bjc.2014.590. Epub 2014 Nov 25.
• [9] Association of rs5764455 and rs6006473 polymorphisms in PARVB with liver damage of nonalcoholic fatty liver disease in Han Chinese population.Gene. 2016 Jan 10;575(2 Pt 1):270-5. doi: 10.1016/j.gene.2015.09.007. Epub 2015 Sep 4.
• [10] Interstitial 22q13 deletions not involving SHANK3 gene: a new contiguous gene syndrome.Am J Med Genet A. 2014 Jul;164A(7):1666-76. doi: 10.1002/ajmg.a.36513. Epub 2014 Apr 3.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] 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.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells. PLoS One. 2011 Apr 4;6(4):e18306. doi: 10.1371/journal.pone.0018306.
• [18] Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer. 2014 Sep 9;111(6):1241-8. doi: 10.1038/bjc.2014.430. Epub 2014 Aug 12.