Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUK67IT)

• DOT Name: Advillin (AVIL)
• Synonyms: p92
• Gene Name: AVIL
• Related Disease:
  Inflammatory bowel disease
  Nervous system inflammation
  Neuralgia
  Peripheral neuropathy
  Steroid-resistant nephrotic syndrome
  Nephrotic syndrome, type 21
• UniProt ID: AVIL_HUMAN
• PDB ID: 1UND
• Pfam ID: PF00626 ; PF02209
• Sequence:
  MPLTSAFRAVDNDPGIIVWRIEKMELALVPVSAHGNFYEGDCYVILSTRRVASLLSQDIH
  FWIGKDSSQDEQSCAAIYTTQLDDYLGGSPVQHREVQYHESDTFRGYFKQGIIYKQGGVA
  SGMKHVETNTYDVKRLLHVKGKRNIRATEVEMSWDSFNRGDVFLLDLGKVIIQWNGPESN
  SGERLKAMLLAKDIRDRERGGRAKIGVIEGDKEAASPELMKVLQDTLGRRSIIKPTVPDE
  IIDQKQKSTIMLYHISDSAGQLAVTEVATRPLVQDLLNHDDCYILDQSGTKIYVWKGKGA
  TKAEKQAAMSKALGFIKMKSYPSSTNVETVNDGAESAMFKQLFQKWSVKDQTMGLGKTFS
  IGKIAKVFQDKFDVTLLHTKPEVAAQERMVDDGNGKVEVWRIENLELVPVEYQWYGFFYG
  GDCYLVLYTYEVNGKPHHILYIWQGRHASQDELAASAYQAVEVDRQFDGAAVQVRVRMGT
  EPRHFMAIFKGKLVIFEGGTSRKGNAEPDPPVRLFQIHGNDKSNTKAVEVPAFASSLNSN
  DVFLLRTQAEHYLWYGKGSSGDERAMAKELASLLCDGSENTVAEGQEPAEFWDLLGGKTP
  YANDKRLQQEILDVQSRLFECSNKTGQFVVTEITDFTQDDLNPTDVMLLDTWDQVFLWIG
  AEANATEKESALATAQQYLHTHPSGRDPDTPILIIKQGFEPPIFTGWFLAWDPNIWSAGK
  TYEQLKEELGDAAAIMRITADMKNATLSLNSNDSEPKYYPIAVLLKNQNQELPEDVNPAK
  KENYLSEQDFVSVFGITRGQFAALPGWKQLQMKKEKGLF
• Function: Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling. May have a unique function in the morphogenesis of neuronal cells which form ganglia. Required for SREC1-mediated regulation of neurite-like outgrowth. Plays a role in regenerative sensory axon outgrowth and remodeling processes after peripheral injury in neonates. Involved in the formation of long fine actin-containing filopodia-like structures in fibroblast. Plays a role in ciliogenesis. In podocytes, controls lamellipodia formation through the regulation of EGF-induced diacylglycerol generation by PLCE1 and ARP2/3 complex assembly.
• Tissue Specificity: Most highly expressed in the small intestine and colonic lining. Weaker expression also detected in the thymus, prostate, testes and uterus . Expressed in podocytes (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[1]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[2]
Neuralgia	DISWO58J	Strong	Biomarker	[2]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[2]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Biomarker	[3]
Nephrotic syndrome, type 21	DISI9EGO	Limited	Unknown	[3]

7 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 Advillin (AVIL).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Advillin (AVIL).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Advillin (AVIL).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Advillin (AVIL).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Advillin (AVIL).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Advillin (AVIL).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Advillin (AVIL).	[11]

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 Advillin (AVIL).	[9]

References

• [1] Genomic structure, chromosome mapping and expression analysis of the human AVIL gene, and its exclusion as a candidate for locus for inflammatory bowel disease at 12q13-14 (IBD2).Gene. 2002 Apr 17;288(1-2):179-85. doi: 10.1016/s0378-1119(02)00478-x.
• [2] Involvement of advillin in somatosensory neuron subtype-specific axon regeneration and neuropathic pain.Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8557-E8566. doi: 10.1073/pnas.1716470115. Epub 2018 Aug 20.
• [3] Advillin acts upstream of phospholipase C ?1 in steroid-resistant nephrotic syndrome. J Clin Invest. 2017 Dec 1;127(12):4257-4269. doi: 10.1172/JCI94138. Epub 2017 Oct 23.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] 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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.