Defensin alpha 5

experimental

Also known as: Defensin-5, HD5(20-94), DEFA5, Q01523

**Mechanism of Action** Defensin alpha 5 (HD5) is a host-defense peptide constitutively expressed in Paneth cells of the small intestine and epithelial cells of the urogenital tract. It exerts antimicrobial activity by disrupting microbial membranes through electrostatic interactions with negatively charged phospholipids, leading to pore formation and cell lysis. HD5 also modulates innate immunity by chemotactic recruitment of immune cells and regulation of inflammatory signaling, contributing to sterility maintenance in the urogenital system. **Key Research Findings** Preclinical studies demonstrate HD5's broad-spectrum activity against Gram-positive and Gram-negative bacteria, fungi, and enveloped viruses, including uropathogenic *E. coli* and *Candida* species. Research highlights its role in preventing ascending urinary tract infections and maintaining gut microbial homeostasis. Reduced HD5 expression is associated with inflammatory bowel disease and increased susceptibility to urogenital infections. Experimental models show HD5 can synergize with conventional antibiotics, reducing required doses and mitigating resistance development. **Clinical Relevance** HD5 is under investigation as a topical or systemic therapeutic for multidrug-resistant infections, particularly in urogenital and gastrointestinal contexts. Its potential as a biomarker for intestinal inflammation and infection risk is being explored. Challenges include proteolytic degradation and cytotoxicity at high concentrations, necessitating formulation strategies for clinical translation. Current status remains experimental, with no approved human therapies. For research purposes only — not medical advice.

Key data

Category
Immune Modulation
Sequence
MRTIAILAAILLVALQAQAESLQERADEATTQKQSGEDNQDLAISFAGNGLSALRTSGSQARATCYCRTGRCATRESLSGVCEISGRLYRLCCR
Molecular weight
10071 g/mol
Research status
experimental
References
10
Tags
uniprot, 3d-structure, antibiotic, antimicrobial, cytoplasmic-vesicle, defensin, direct-protein-sequencing, disulfide-bond, fungicide, glycoprotein, immunity, innate-immunity

Mechanism of action

Host-defense peptide that maintains sterility in the urogenital system (PubMed:12021776, PubMed:12660734, PubMed:15616305, PubMed:19589339, PubMed:22359618, PubMed:22573326, PubMed:25354318, PubMed:25782105, PubMed:30808760). Has antimicrobial activity against a wide range of bacteria, including Gram-negative E.coli, P.aeruginosa and S.typhimurium, and Gram-positive E.aerogenes, S.aureus, B.cereus, E.faecium and L.monocytogenes (PubMed:12021776, PubMed:15616305, PubMed:19589339, PubMed:22359618, PubMed:22573326, PubMed:25354318, PubMed:30808760). Confers resistance to intestinal infection by S.typhimurium (PubMed:12660734). Exhibits antimicrobial activity against enteric commensal bacteria such as B.adolescentis, L.acidophilus, B.breve, L.fermentum, B.longum and S.thermophilus (PubMed:25354318). Binds to bacterial membranes and causes membrane disintegration (PubMed:25782105). Induces the secretion of the chemokine IL-8 by intestinal epithelial cells (PubMed:19589339). Binds to B.antracis lef/lethal factor, a major virulence factor from B.anthracis, and neutralizes its enzymatic activity (PubMed:22573326)

Research & studies

Afatinib alters DNA methylation and Paneth-like differentiation markers in Caco-2 cells
Advances in biological regulation · 2026 · PubMed
A multi-omics study to investigate the progression of the Correa pathway in gastric mucosa in the context of cirrhosis
Gut pathogens · 2023 · PubMed
Reduced DEFA5 Expression and STAT3 Activation Underlie the Submucosal Invasion of Early Gastric Cancers
Digestion · 2023 · PubMed
Electroacupuncture promoted intestinal defensins and rescued the dysbiotic cecal microbiota of high-fat diet-induced obese mice
Life sciences · 2022 · PubMed

Electroacupuncture effectively reduced body weight and fat accumulation in obese mice on a high-fat diet.; Full-length 16S rDNA sequencing showed dysbiotic cecal microbiota in obese mice, which was restored after electroacupuncture treatment.; Electroacupuncture increased defensin alpha 5 expression to healthy control levels and decreased fat digestion and absorption genes like fabp1 in the jejunum.; Defensin alpha 5 levels positively correlated with Lachnospiraceae family and negatively correlated with obesity indexes.

Toll-like receptor 4-mediated endoplasmic reticulum stress induces intestinal paneth cell damage in mice following CLP-induced sepsis
Scientific reports · 2022 · PubMed

CLP-induced sepsis increased ileal TLR4 expression by more than five-fold, correlating with higher mortality and murine sepsis scores.; Paneth cell numbers and expression of lysozyme and defensin alpha 5 were reduced in septic mice.; ER stress markers ATF6, XBP1, and CHOP were upregulated, with increased cleavage of ATF6 from p90 to p50 form.; TAK-242 treatment improved intestinal mucosal injury and reduced ER stress marker expression, suggesting TLR4 drives Paneth cell damage via ATF6/CHOP pathway.

High level of defensin alpha 5 in intestine may explain the low incidence of diarrhoea in COVID-19 patients
European journal of gastroenterology & hepatology · 2022 · PubMed
Human α-defensin 5 suppressed colon cancer growth by targeting PI3K pathway
Experimental cell research · 2021 · PubMed

DEFA5 protein expression is decreased in colon cancer tissues.; DEFA5 overexpression suppresses colon cancer cell proliferation and colony formation.; DEFA5 overexpression inhibits tumor growth in nude mouse xenograft models.; DEFA5 directly binds to PI3K complex subunits, attenuating downstream signaling and metastasis.

DNA Methylation of TLR4, VEGFA, and DEFA5 Is Associated With Necrotizing Enterocolitis in Preterm Infants
Frontiers in pediatrics · 2021 · PubMed

Frequently asked questions

What is Defensin alpha 5?

**Mechanism of Action** Defensin alpha 5 (HD5) is a host-defense peptide constitutively expressed in Paneth cells of the small intestine and epithelial cells of the urogenital tract. It exerts antimicrobial activity by disrupting microbial membranes through electrostatic interactions with negatively charged phospholipi

How does Defensin alpha 5 work?

Host-defense peptide that maintains sterility in the urogenital system (PubMed:12021776, PubMed:12660734, PubMed:15616305, PubMed:19589339, PubMed:22359618, PubMed:22573326, PubMed:25354318, PubMed:25782105, PubMed:30808760). Has antimicrobial activity against a wide range of bacteria, including Gram-negative E.coli, P.aeruginosa and S.typhimurium, and Gram-positive E.aerogenes, S.aureus, B.cereus

What is the research status of Defensin alpha 5?

Defensin alpha 5 is currently classified as experimental, with 10 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Defensin alpha 5?

Defensin alpha 5 has a molecular weight of approximately 10071 g/mol.

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    Defensin alpha 5 — Mechanism, Research & Data | Peptides API