Histatin-3 (HTN3)

Histatin-3 is a small, histidine-rich, cationic antimicrobial peptide found in human saliva, primarily encoded by the HTN3 gene. It is a member of the histatin family and acts as a precursor for multiple related peptides (e.g., histatins 4–6) via post-translational proteolytic processing[1][2][3]. Histatin-3 and its derived peptides play a crucial role in the innate immune defense of the oral cavity, with functions that include direct antimicrobial activity against bacteria and fungi (especially *Candida albicans*), wound healing, and formation of a proteinaceous protective film on tooth enamel[1][2][3]. The antimicrobial action includes disruption of microbial membranes and deprivation of essential ions, and some fragments can bind and inhibit proteases associated with pathogenic bacteria and the host[2][3]. Histatin-3 is not a classical drug target such as a receptor or enzyme but is being explored as a model for designing new antimicrobial therapies and as a biomarker for oral and systemic health assessment[3].

Other names

Histatin 3HTN3Histatin-3HIS2HstHst 3Basic histidine-rich proteinHistidine-rich protein 3Histatin-4Histatin-5Histatin-6Histatin-7Histatin-8Histatin-9Histatin-10Histatin-11Histatin-12numerous peptide fragment names (His3-(20-44)-peptide, etc.)

Direct antimicrobial effect via plasma membrane disruption and loss of intracellular content in microbes; Binds fungal potassium transporter Trk1, causing ion imbalance and cell death (mainly for certain fragments, such as histatin-5); Inhibits microbial and human proteases (e.g., gingipains, MMP2, MMP9)