Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF1A4N0)

• DOT Name: F-actin-capping protein subunit beta (CAPZB)
• Synonyms: CapZ beta
• Gene Name: CAPZB
• Related Disease:
  Carcinoma
  Autoimmune disease
  Brain cancer
  Brain neoplasm
  Hypothyroidism
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Undifferentiated carcinoma
  Acute coronary syndrome
• UniProt ID: CAPZB_HUMAN
• PDB ID: 8F8Q
• Pfam ID: PF01115
• Sequence:
  MSDQQLDCALDLMRRLPPQQIEKNLSDLIDLVPSLCEDLLSSVDQPLKIARDKVVGKDYL
  LCDYNRDGDSYRSPWSNKYDPPLEDGAMPSARLRKLEVEANNAFDQYRDLYFEGGVSSVY
  LWDLDHGFAGVILIKKAGDGSKKIKGCWDSIHVVEVQEKSSGRTAHYKLTSTVMLWLQTN
  KSGSGTMNLGGSLTRQMEKDETVSDCSPHIANIGRLVEDMENKIRSTLNEIYFGKTKDIV
  NGLRSVQTFADKSKQEALKNDLVEALKRKQQC
• Function: F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOF GTPase cycle (R-HSA-9035034)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[2]
Brain cancer	DISBKFB7	Strong	Genetic Variation	[3]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[3]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[5]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[6]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[5]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[1]
Acute coronary syndrome	DIS7DYEW	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	F-actin-capping protein subunit beta (CAPZB) affects the binding of 4-hydroxy-2-nonenal.	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of F-actin-capping protein subunit beta (CAPZB).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of F-actin-capping protein subunit beta (CAPZB).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of F-actin-capping protein subunit beta (CAPZB).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of F-actin-capping protein subunit beta (CAPZB).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of F-actin-capping protein subunit beta (CAPZB).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of F-actin-capping protein subunit beta (CAPZB).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of F-actin-capping protein subunit beta (CAPZB).	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of F-actin-capping protein subunit beta (CAPZB).	[15]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of F-actin-capping protein subunit beta (CAPZB).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of F-actin-capping protein subunit beta (CAPZB).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of F-actin-capping protein subunit beta (CAPZB).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of F-actin-capping protein subunit beta (CAPZB).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of F-actin-capping protein subunit beta (CAPZB).	[20]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of F-actin-capping protein subunit beta (CAPZB).	[21]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of F-actin-capping protein subunit beta (CAPZB).	[22]

1 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 increases the methylation of F-actin-capping protein subunit beta (CAPZB).	[18]

References

• [1] Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
• [2] Novel associations for hypothyroidism include known autoimmune risk loci.PLoS One. 2012;7(4):e34442. doi: 10.1371/journal.pone.0034442. Epub 2012 Apr 6.
• [3] Germline mutations in the p73 gene do not predispose to familial prostate-brain cancer.Prostate. 2001 Sep 15;48(4):292-6. doi: 10.1002/pros.1109.
• [4] Expression of F-actin-capping protein subunit beta, CAPZB, is associated with cell growth and motility in epithelioid sarcoma.BMC Cancer. 2016 Mar 10;16:206. doi: 10.1186/s12885-016-2235-z.
• [5] Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway.Mol Cancer. 2006 Mar 1;5:9. doi: 10.1186/1476-4598-5-9.
• [6] The complex genetic epidemiology of prostate cancer.Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21. doi: 10.1093/hmg/ddh072. Epub 2004 Jan 28.
• [7] Proteomic changes related to "bewildered" circulating platelets in the acute coronary syndrome.Proteomics. 2011 Aug;11(16):3335-48. doi: 10.1002/pmic.201000708. Epub 2011 Jul 14.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] 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.
• [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] Gene expression profile changes in NB4 cells induced by arsenic trioxide. Acta Pharmacol Sin. 2003 Jul;24(7):646-50.
• [14] 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.
• [15] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [16] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [17] 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.
• [18] 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.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [21] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [22] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [23] Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: protein carbonylation is diminished by ascorbic acid. Chem Res Toxicol. 2010 Jan;23(1):37-47. doi: 10.1021/tx9002462.