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Histatins are histidine-rich (cationic) antimicrobial proteins found in saliva.[1] Histatin's involvement in antimicrobial activities makes histatin part of the innate immune system.[2]

Histatin was first discovered (isolated) in 1988, with functions that's responsible in keeping homeostasis inside the oral cavity, helping in the formation of pellicles, and assist in bonding of metal ions.[3]


The structure of histatin is unique depending on whether the protein of interest is histatin 1, 3 or 5. Nonetheless, histatin mainly possess a cationic charge due to the primary structure consisting mostly of basic amino acids. An amino acid that is crucial to histatin's function is histidine. Studies show that the removal of histadine (especially in histatin 5) resulted in reduction of antifungal activity.[4]


Histatins are antimicrobial and antifungal proteins, and have been found to play a role in wound-closure.[5][6] A significant source of histatins is found in the serous fluid secreted by Ebner's glands, salivary glands at the back of the tongue, and produced by Acinus cells.[7] Here they offer some early defense against incoming microbes.[8]

The three major histatins are 1, 3, and 5, which contains 38, 32, and 24 amino acids, respectively. Histatin 2 is a degradation product of histatin 1, and all other histatins are degradation products of histatin 3 through the process of post-translational proteolysis of the HTN3 gene.[9] Therefore there are only two genes, HTN1 and HTN3.

Histatin 5 N-terminus allows it to bind with metals because of its highly reactive nature. It's been shown that this chemical nature allows the precipitate of reactive oxygen species.[3]

Histatin's antifungal properties has been seen with fungus such as Candida glabrata, Candida krusei, Saccharomyces cerevisiae, and Cryptococcus neoformans.[10]

Histatins also precipitate tannins from solution - thus preventing alimentary adsorption.[11]

Histatin's anti-fungal property works by the release of the fungal's intracellular component through the disruption of the fungus plasma membrane.[7] They also work against yeast, by binding to the potassium transporter and facilitating in the loss of azole-resistant species.[12]


  1. ^ Histatins at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ Qin Y, Zhang L, Xu Z, Zhang J, Jiang YY, Cao Y, Yan T (July 2016). "Innate immune cell response upon Candida albicans infection". Virulence. 7 (5): 512–26. doi:10.1080/21505594.2016.1138201. PMC 5026795. PMID 27078171.
  3. ^ a b Khurshid, Zohaib; Najeeb, Shariq; Mali, Maria; Moin, Syed Faraz; Raza, Syed Qasim; Zohaib, Sana; Sefat, Farshid; Zafar, Muhammad Sohail (January 2017). "Histatin peptides: Pharmacological functions and their applications in dentistry". Saudi Pharmaceutical Journal. 25 (1): 25–31. doi:10.1016/j.jsps.2016.04.027. PMC 5310145. PMID 28223859.
  4. ^ Edgerton, Mira; Jang, Woong Sik (2012-01-01). "Salivary Histatins: Structure, Function, and Mechanisms of Antifungal Activity". Candida and Candidiasis, Second Edition. pp. 185–194. doi:10.1128/9781555817176.ch13. ISBN 978-1-55581-539-4.
  5. ^ Kavanagh K, Dowd S (March 2004). "Histatins: antimicrobial peptides with therapeutic potential" (PDF). The Journal of Pharmacy and Pharmacology. 56 (3): 285–9. doi:10.1211/0022357022971. PMID 15025852.
  6. ^ Oudhoff MJ, Bolscher JG, Nazmi K, Kalay H, van 't Hof W, Amerongen AV, Veerman EC (November 2008). "Histatins are the major wound-closure stimulating factors in human saliva as identified in a cell culture assay". FASEB Journal. 22 (11): 3805–12. doi:10.1096/fj.08-112003. PMID 18650243.
  7. ^ a b Oppenheim FG, Xu T, McMillian FM, Levitz SM, Diamond RD, Offner GD, Troxler RF (June 1988). "Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans". The Journal of Biological Chemistry. 263 (16): 7472–7. PMID 3286634.
  8. ^ Piludu M, Lantini MS, Cossu M, Piras M, Oppenheim FG, Helmerhorst EJ, Siqueira W, Hand AR (November 2006). "Salivary histatins in human deep posterior lingual glands (of von Ebner)". Archives of Oral Biology. 51 (11): 967–73. doi:10.1016/j.archoralbio.2006.05.011. PMID 16859632.
  9. ^ Khurshid Z, Najeeb S, Mali M, Moin SF, Raza SQ, Zohaib S, Sefat F, Zafar MS (January 2017). "Histatin peptides: Pharmacological functions and their applications in dentistry". Saudi Pharmaceutical Journal. 25 (1): 25–31. doi:10.1016/j.jsps.2016.04.027. PMC 5310145. PMID 28223859.
  10. ^ Tsai H, Bobek LA (October 1997). "Human salivary histatin-5 exerts potent fungicidal activity against Cryptococcus neoformans". Biochimica et Biophysica Acta (BBA) - General Subjects. 1336 (3): 367–9. doi:10.1016/S0304-4165(97)00076-7. PMID 9367163.
  11. ^ Shimada T (June 2006). "Salivary proteins as a defense against dietary tannins". Journal of Chemical Ecology. 32 (6): 1149–63. doi:10.1007/s10886-006-9077-0. PMID 16770710.
  12. ^ Swidergall, Marc; Ernst, Joachim F. (August 2014). "Interplay between Candida albicans and the Antimicrobial Peptide Armory". Eukaryotic Cell. 13 (8): 950–957. doi:10.1128/EC.00093-14. PMC 4135787. PMID 24951441.