Defensin beta 4A

experimental

Also known as: Beta-defensin 2, Defensin, beta 2, Skin-antimicrobial peptide 1, DEFB4A, DEFB4B, O15263

Defensin beta 4A (DEFB4A), also known as beta-defensin 2, is an antimicrobial peptide primarily expressed in epithelial tissues, particularly the skin and respiratory tract. Its mechanism of action involves disrupting microbial cell membranes through electrostatic interactions, leading to pore formation and cell lysis. It exhibits broad-spectrum antimicrobial activity, with highest potency against Gram-negative bacteria, though it is also effective against Gram-positive bacteria and some fungi. Additionally, DEFB4A functions as a chemoattractant for immune cells, linking innate and adaptive immunity. Key research findings indicate that DEFB4A expression is upregulated in response to inflammatory stimuli, such as bacterial lipopolysaccharides and cytokines like TNF-α and IL-1β. Studies have demonstrated its role in wound healing and mucosal defense, with reduced expression associated with increased susceptibility to infections in conditions like atopic dermatitis and cystic fibrosis. Experimental models also suggest potential involvement in cancer modulation, though data remain preliminary. Clinically, DEFB4A is being investigated as a biomarker for inflammatory and infectious diseases, as well as a template for novel antimicrobial therapies. Its selective activity against pathogens and low propensity for inducing resistance make it a candidate for topical or systemic applications. However, its therapeutic use remains experimental, with no approved indications. For research purposes only — not medical advice.

Key data

Category
Immune Modulation
Sequence
MRVLYLLFSFLFIFLMPLPGVFGGIGDPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCKKP
Molecular weight
7038 g/mol
Research status
experimental
References
7
Tags
uniprot, 3d-structure, antibiotic, antimicrobial, defensin, disulfide-bond, proteomics-identification, reference-proteome, secreted, signal

Mechanism of action

Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria, with highest activity against Gram-negative bacteria (PubMed:10837369, PubMed:9202117). Antimicrobial activity against P.aeruginosa seems to be salt-sensitive and is reduced with high salt concentrations greater than 25 mM (PubMed:10837369). Also exhibits antimicrobial activity against the yeast C.albicans (PubMed:10837369, PubMed:30050988, PubMed:9202117). Permeabilizes C.albicans cell membranes via targeting plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), thereby leading to cell fragmentation and cell death (PubMed:30050988). Acts as a ligand for C-C chemokine receptor CCR6 (PubMed:10521347, PubMed:20068036). Binds to CCR6 and induces chemotactic activity of CCR6-expressing cells, such as immature dendritic cells and memory T cells (PubMed:10521347, PubMed:20068036)

Research & studies

Importance of PLD2 in an IL-23 driven psoriasiform dermatitis model and potential link to human psoriasis
The Journal of dermatology · 2023 · PubMed

PLD2 gene expression is significantly higher in lesional skin of psoriasis patients compared to non-lesional or healthy skin.; PLD2 deficiency reduced ear thickness, defensin beta 4A, S100A7A, macrophage infiltrate, and CXCL10/IL-6 in the IL-23 mouse model.; Type 17 cytokines IL-17A and IL-17F were not reduced by PLD2 deficiency.; Dual knockout of PLD1 and PLD2 offered little additional protection over PLD2 knockout alone.

Down regulation of defensin genes during SARS-CoV-2 infection
Acta virologica · 2022 · PubMed

Nine defensin genes were expressed in the nasopharyngeal/oropharyngeal cavity.; Four defensin genes (beta 4A/B, 106B, 107B, and 103A) were significantly downregulated in SARS-CoV-2 infected patients.; Downregulation of human beta defensin 2, 3, 6, and 7 indicates potential compromise of antiviral innate immune response.; Defensin peptide-based therapy may be an attractive treatment approach to correct downregulation.

SPRR2C, DEFB4A, WIF1, CRY2, and KRT19 are correlated with the development of atopic eczema
European review for medical and pharmacological sciences · 2021 · PubMed
DEFB4A is a potential prognostic biomarker for colorectal cancer
Oncology letters · 2020 · PubMed

DEFB4A and HABP2 were upregulated in colorectal cancer tumor tissues.; DEFB4A was associated with immunosuppression and correlated with CD11b, CD14, CD45, CD163, and IL17A.; High DEFB4A expression was linked to larger tumors, advanced stage, lymph node and liver metastasis, and poor survival.; Knockdown of DEFB4A reduced cell migration in vitro.

Ichthyosis molecular fingerprinting shows profound T(H)17 skewing and a unique barrier genomic signature
The Journal of allergy and clinical immunology · 2019 · PubMed
RNA-Seq analysis of non-small cell lung cancer in female never-smokers reveals candidate cancer-associated long non-coding RNAs
Pathology, research and practice · 2016 · PubMed
Identification of novel immune and barrier genes in atopic dermatitis by means of laser capture microdissection
The Journal of allergy and clinical immunology · 2015 · PubMed

Frequently asked questions

What is Defensin beta 4A?

Defensin beta 4A (DEFB4A), also known as beta-defensin 2, is an antimicrobial peptide primarily expressed in epithelial tissues, particularly the skin and respiratory tract. Its mechanism of action involves disrupting microbial cell membranes through electrostatic interactions, leading to pore formation and cell lysis.

How does Defensin beta 4A work?

Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria, with highest activity against Gram-negative bacteria (PubMed:10837369, PubMed:9202117). Antimicrobial activity against P.aeruginosa seems to be salt-sensitive and is reduced with high salt concentrations greater than 25 mM (PubMed:10837369). Also exhibits antimicrobial activity against the yeast C.albicans (

What is the research status of Defensin beta 4A?

Defensin beta 4A is currently classified as experimental, with 7 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Defensin beta 4A?

Defensin beta 4A has a molecular weight of approximately 7038 g/mol.

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