Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQEI15K)

• DOT Name: Defensin beta 4A (DEFB4A)
• Synonyms: Beta-defensin 2; BD-2; hBD-2; Defensin, beta 2; Skin-antimicrobial peptide 1; SAP1
• Gene Name: DEFB4A
• UniProt ID: DFB4A_HUMAN
• PDB ID: 1E4Q; 1FD3; 1FD4; 1FQQ; 6CS9
• Pfam ID: PF00711
• Sequence:
  MRVLYLLFSFLFIFLMPLPGVFGGIGDPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKC
  CKKP
• Function: Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria, with highest activity against Gram-negative bacteria. Antimicrobial activity against P.aruginosa seems to be salt-sensitive and is reduced with high salt concentrations greater than 25 mM. Also exhibits antimicrobial activity against the yeast C.albicans. Permeabilizes C.albicans cell membranes via targeting plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), thereby leading to cell fragmentation and cell death. Acts as a ligand for C-C chemokine receptor CCR6. Binds to CCR6 and induces chemotactic activity of CCR6-expressing cells, such as immature dendritic cells and memory T cells.
• Tissue Specificity: Expressed in lung epithelial cells (at protein level) . Expressed in foreskin, lung and trachea . Lower expression in kidney, uterus and salivary gland tissue . Expressed in epithelial cells of the respiratory tract, with higher expression in distal parenchyma of the lung, trachea, and tonsils, and lower expression in pharynx and adenoid, and low expression in tongue and larynx .
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  IL-17 sig.ling pathway (hsa04657)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Defensins (R-HSA-1461973)
  Beta defensins (R-HSA-1461957)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Defensin beta 4A (DEFB4A).	[1]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of Defensin beta 4A (DEFB4A).	[2]
Oxindole 94	DMPFD6Y	Investigative	Oxindole 94 decreases the expression of Defensin beta 4A (DEFB4A).	[3]

References

• [1] Modulation of human beta-defensin-2 expression by 17beta-estradiol and progesterone in vaginal epithelial cells. Cytokine. 2010 Feb;49(2):209-14. doi: 10.1016/j.cyto.2009.09.005. Epub 2009 Oct 9.
• [2] Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells. Clin Exp Immunol. 2012 Apr;168(1):113-24. doi: 10.1111/j.1365-2249.2011.04549.x.
• [3] Role of SIRT1 in Streptococcus pneumoniae-induced human -defensin-2 and interleukin-8 expression in A549 cell. Mol Cell Biochem. 2014 Sep;394(1-2):199-208. doi: 10.1007/s11010-014-2095-2. Epub 2014 Jun 4.