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Gene Review

HTN1  -  histatin 1

Homo sapiens

Synonyms: HIS1, Histatin-1, Histidine-rich protein 1, PPB, Post-PB protein
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Disease relevance of HTN1


Psychiatry related information on HTN1

  • Other fish at 125 PPB exhibited transient lethargy and increased opercular movement but recovered within 24 hr [6].

High impact information on HTN1


Chemical compound and disease context of HTN1


Biological context of HTN1


Anatomical context of HTN1


Associations of HTN1 with chemical compounds

  • The results suggest that the anticandidal properties of histatin 5 could be impaired by the conformations resulting from mineral adsorption, or that putative cellular receptors necessary for candidacidal activity are inaccessible when histatin 5 is adsorbed on hydroxyapatite [17].
  • Native histatin 1 (containing a phosphoserine at residue 2) was purified from parotid saliva, whereas a bacterial expression system was used to produce a recombinant form of histatin 1 (re-Hst1) that lacked phosphorylated serine [24].
  • Histatin 5 has no defined structure in H2O but adopts a more helical conformation in dimethyl sulfoxide and aqueous trifluoroethanol [25].
  • Divergent solid-phase synthesis and candidacidal activity of MUC7 D1, a 51-residue histidine-rich N-terminal domain of human salivary mucin MUC7 [26].
  • Lack of detection of C-terminal fragments, with the exception of 26-32, 28-32, and 29-32 fragments, suggested that arginine 25 should be the first cleavage site, generating histatin 6 and 26-32 fragments [27].

Physical interactions of HTN1


Regulatory relationships of HTN1

  • The results showed that only salivary statherin and egg yolk phosvitin promote histatin 5 adsorption significantly [28].
  • The dramatic conservation of the 5' non-coding region between the feather keratin sequences and an unrelated but co-expressed gene encoding a histidine-rich protein suggests that this segment may play an important role in transcriptional regulation [33].
  • Histatin 5 strongly inhibited a trypsin-like protease produced by Bacteroides gingivalis with an IC50 value of 55 nM [34].
  • As the morphological defects induced by histatin 5 are much smaller than those induced by LL-37, but the efflux of nucleotides is similar at comparable candidacidal concentrations, we suggest that the loss of nucleotides plays an important role in the killing process [35].

Other interactions of HTN1

  • The structural data suggest that histatins 1 and 3 are derived from different structural genes, whereas histatin 5 is a proteolytic product of histatin 3 [36].
  • The HIS1 sequence data were also compared with that of STATH [1].
  • MUC7 12-mer (residues 40-51 of the parent MUC7) peptide, having the optimal size and a net charge of +6, was found to be anticandidal in human saliva (clarified and unclarified), and its candidacidal potency was found to be superior to that of histatin 5 12-mer (Hsn5 12-mer) [37].
  • Comparison of inhibitory activity on calcium phosphate precipitation by acidic proline-rich proteins, statherin, and histatin-1 [38].
  • Tissue-type plasminogen activator, plasminogen activator inhibitor, and histidine-rich glycoproteins in stressed human newborns [39].

Analytical, diagnostic and therapeutic context of HTN1


  1. Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family. Sabatini, L.M., Ota, T., Azen, E.A. Mol. Biol. Evol. (1993) [Pubmed]
  2. Expression of human salivary histatin and cystatin/histatin chimeric cDNAs in Escherichia coli. Bobek, L.A., Tsai, H., Levine, M.J. Crit. Rev. Oral Biol. Med. (1993) [Pubmed]
  3. Statherin and histatin 1 reduce parotid saliva-promoted Streptococcus mutans strain MT8148 adhesion to hydroxyapatite surfaces. Shimotoyodome, A., Kobayashi, H., Tokimitsu, I., Matsukubo, T., Takaesu, Y. Caries Res. (2006) [Pubmed]
  4. Efficacy of human salivary mucin MUC7-derived peptide and histatin 5 in a murine model of candidiasis. Intini, G., Aguirre, A., Bobek, L.A. Int. J. Antimicrob. Agents (2003) [Pubmed]
  5. The role of salivary peptides in dental caries. Vitorino, R., Lobo, M.J., Duarte, J.R., Ferrer-Correia, A.J., Domingues, P.M., Amado, F.M. Biomed. Chromatogr. (2005) [Pubmed]
  6. Safety of milbemycin as an oral or bath treatment for the tropical freshwater angelfish Pterophyllum scalare. Killino, T.J., Bodri, M.S. J. Zoo Wildl. Med. (1997) [Pubmed]
  7. A chromosomal rearrangement in a P. falciparum histidine-rich protein gene is associated with the knobless phenotype. Pologe, L.G., Ravetch, J.V. Nature (1986) [Pubmed]
  8. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Eckner, R., Ewen, M.E., Newsome, D., Gerdes, M., DeCaprio, J.A., Lawrence, J.B., Livingston, D.M. Genes Dev. (1994) [Pubmed]
  9. Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex. German, M.S., Wang, J., Chadwick, R.B., Rutter, W.J. Genes Dev. (1992) [Pubmed]
  10. Arabidopsis FAD2 gene encodes the enzyme that is essential for polyunsaturated lipid synthesis. Okuley, J., Lightner, J., Feldmann, K., Yadav, N., Lark, E., Browse, J. Plant Cell (1994) [Pubmed]
  11. Cooperative domains define a unique host cell-targeting signal in Plasmodium falciparum-infected erythrocytes. Lopez-Estraño, C., Bhattacharjee, S., Harrison, T., Haldar, K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Salivary histatin 5 is a potent competitive inhibitor of the cysteine proteinase clostripain. Gusman, H., Grogan, J., Kagan, H.M., Troxler, R.F., Oppenheim, F.G. FEBS Lett. (2001) [Pubmed]
  13. Relation of DDE and PBB serum levels in farm residents, consumers, and Michigan Chemical Corporation employees. Wolff, M.S., Aubrey, B., Camper, F., Haymes, N. Environ. Health Perspect. (1978) [Pubmed]
  14. Detection of histidine rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia. Tjitra, E., Suprianto, S., Dyer, M.E., Currie, B.J., Anstey, N.M. Am. J. Trop. Med. Hyg. (2001) [Pubmed]
  15. Short report: Field evaluation of posttreatment sensitivity for monitoring parasite clearance of Plasmodium falciparum malaria by use of the Determine Malaria pf test in central India. Singh, N., Shukla, M.M. Am. J. Trop. Med. Hyg. (2002) [Pubmed]
  16. Clinical and microbial evaluation of a histatin-containing mouthrinse in humans with experimental gingivitis. Mickels, N., McManus, C., Massaro, J., Friden, P., Braman, V., D'Agostino, R., Oppenheim, F., Warbington, M., Dibart, S., Van Dyke, T. Journal of clinical periodontology. (2001) [Pubmed]
  17. Physical parameters of hydroxyapatite adsorption and effect on candidacidal activity of histatins. Yin, A., Margolis, H.C., Grogan, J., Yao, Y., Troxler, R.F., Oppenheim, F.G. Arch. Oral Biol. (2003) [Pubmed]
  18. Histatin 3-mediated killing of Candida albicans: effect of extracellular salt concentration on binding and internalization. Xu, Y., Ambudkar, I., Yamagishi, H., Swaim, W., Walsh, T.J., O'Connell, B.C. Antimicrob. Agents Chemother. (1999) [Pubmed]
  19. Localization of the genes for histatins to human chromosome 4q13 and tissue distribution of the mRNAs. vanderSpek, J.C., Wyandt, H.E., Skare, J.C., Milunsky, A., Oppenheim, F.G., Troxler, R.F. Am. J. Hum. Genet. (1989) [Pubmed]
  20. Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Edgerton, M., Koshlukova, S.E., Araujo, M.W., Patel, R.C., Dong, J., Bruenn, J.A. Antimicrob. Agents Chemother. (2000) [Pubmed]
  21. Purification of kinase activity from primate parotid glands. Lamkin, M.S., Lindhe, P. J. Dent. Res. (2001) [Pubmed]
  22. mRNAs for PRPs, statherin, and histatins in von Ebner's gland tissues. Azen, E.A., Hellekant, G., Sabatini, L.M., Warner, T.F. J. Dent. Res. (1990) [Pubmed]
  23. Genetically engineered human salivary histatin genes are functional in Candida albicans: development of a new system for studying histatin candidacidal activity. Baev, D., Li, X., Edgerton, M. Microbiology (Reading, Engl.) (2001) [Pubmed]
  24. Functional comparison of native and recombinant human salivary histatin 1. Driscoll, J., Zuo, Y., Xu, T., Choi, J.R., Troxler, R.F., Oppenheim, F.G. J. Dent. Res. (1995) [Pubmed]
  25. NMR studies of the antimicrobial salivary peptides histatin 3 and histatin 5 in aqueous and nonaqueous solutions. Brewer, D., Hunter, H., Lajoie, G. Biochem. Cell Biol. (1998) [Pubmed]
  26. Divergent solid-phase synthesis and candidacidal activity of MUC7 D1, a 51-residue histidine-rich N-terminal domain of human salivary mucin MUC7. Satyanarayana, J., Situ, H., Narasimhamurthy, S., Bhayani, N., Bobek, L.A., Levine, M.J. J. Pept. Res. (2000) [Pubmed]
  27. A cascade of 24 histatins (histatin 3 fragments) in human saliva. Suggestions for a pre-secretory sequential cleavage pathway. Castagnola, M., Inzitari, R., Rossetti, D.V., Olmi, C., Cabras, T., Piras, V., Nicolussi, P., Sanna, M.T., Pellegrini, M., Giardina, B., Messana, I. J. Biol. Chem. (2004) [Pubmed]
  28. Multi-component adsorption model for pellicle formation: the influence of salivary proteins and non-salivary phospho proteins on the binding of histatin 5 onto hydroxyapatite. Yin, A., Margolis, H.C., Yao, Y., Grogan, J., Oppenheim, F.G. Arch. Oral Biol. (2006) [Pubmed]
  29. Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Freedman, S.J., Sun, Z.Y., Poy, F., Kung, A.L., Livingston, D.M., Wagner, G., Eck, M.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  30. Cloning, tissue distribution, subcellular localization and overexpression of murine histidine-rich Ca2+ binding protein. Ridgeway, A.G., Petropoulos, H., Siu, A., Ball, J.K., Skerjanc, I.S. FEBS Lett. (1999) [Pubmed]
  31. Opposing effects of low and high molecular weight kininogens on cell adhesion. Asakura, S., Yang, W., Sottile, J., Zhang, Q., Jin, Y., Ohkubo, I., Sasaki, M., Matsuda, M., Hirata, H., Mosher, D.F. J. Biochem. (1998) [Pubmed]
  32. Histatin 5 is a substrate and not an inhibitor of the Arg- and Lys-specific proteinases of Porphyromonas gingivalis. O'Brien-Simpson, N.M., Dashper, S.G., Reynolds, E.C. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  33. Avian keratin genes. I. A molecular analysis of the structure and expression of a group of feather keratin genes. Presland, R.B., Gregg, K., Molloy, P.L., Morris, C.P., Crocker, L.A., Rogers, G.E. J. Mol. Biol. (1989) [Pubmed]
  34. Salivary histatin as an inhibitor of a protease produced by the oral bacterium Bacteroides gingivalis. Nishikata, M., Kanehira, T., Oh, H., Tani, H., Tazaki, M., Kuboki, Y. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  35. Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. den Hertog, A.L., van Marle, J., van Veen, H.A., Van't Hof, W., Bolscher, J.G., Veerman, E.C., Nieuw Amerongen, A.V. Biochem. J. (2005) [Pubmed]
  36. Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. Oppenheim, F.G., Xu, T., McMillian, F.M., Levitz, S.M., Diamond, R.D., Offner, G.D., Troxler, R.F. J. Biol. Chem. (1988) [Pubmed]
  37. Antifungal activity of human salivary mucin-derived peptide, MUC7 12-mer, in a murine model of oral candidiasis. Muralidharan, R., Bobek, L.A. J. Pept. Res. (2005) [Pubmed]
  38. Comparison of inhibitory activity on calcium phosphate precipitation by acidic proline-rich proteins, statherin, and histatin-1. Tamaki, N., Tada, T., Morita, M., Watanabe, T. Calcif. Tissue Int. (2002) [Pubmed]
  39. Tissue-type plasminogen activator, plasminogen activator inhibitor, and histidine-rich glycoproteins in stressed human newborns. Corrigan, J.J., Jeter, M.A. Pediatrics (1992) [Pubmed]
  40. An expanded histatin gene polymorphism and test of a possible disease resistant phenotype. Araki, M., Anstey, N.M., Mwaikambo, E.D., Dua, A., Amberger, E., Azen, E.A. Hum. Mutat. (1997) [Pubmed]
  41. Candidacidal activity of human salivary histatin recombinant variants produced by site-directed mutagenesis. Driscoll, J., Duan, C., Zuo, Y., Xu, T., Troxler, R., Oppenheim, F.G. Gene (1996) [Pubmed]
  42. Evaluation of the metal binding properties of the histidine-rich antimicrobial peptides histatin 3 and 5 by electrospray ionization mass spectrometry. Brewer, D., Lajoie, G. Rapid Commun. Mass Spectrom. (2000) [Pubmed]
  43. Characterization of the immunologic responses to human in vivo acquired enamel pellicle as a novel means to investigate its composition. Li, J., Helmerhorst, E.J., Corley, R.B., Luus, L.E., Troxler, R.F., Oppenheim, F.G. Oral Microbiol. Immunol. (2003) [Pubmed]
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