Affinage

HTN1

Histatin-1 · UniProt P15515

Length
57 aa
Mass
7.0 kDa
Annotated
2026-04-28
38 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HTN1 (HIS1) encodes histatin 1, a histidine-rich salivary protein produced in the human parotid gland; histatin 2 is the non-phosphorylated form of histatin 1, indicating that the primary gene product undergoes post-translational phosphorylation (PMID:2719677). The HTN1 gene spans 8.5 kb with six exons and five introns, and it belongs to a small gene family with STATH (statherin) that exhibits accelerated evolution in protein-coding regions, indicating functional specialization from a shared ancestor (PMID:8336540). No direct mechanistic studies of histatin 1 protein function are present in the available primary literature.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 1989 Medium

    Establishing the gene identity of histatin 1: cDNA cloning revealed that at least two loci (HIS1 and HIS2) encode the histatin family, with histatin 2 being the non-phosphorylated form of histatin 1, resolving the molecular basis of histatin protein heterogeneity in saliva.

    Evidence cDNA library screening with synthetic oligonucleotide probes and sequence analysis of 12 parotid gland cDNA clones

    PMID:2719677

    Open questions at the time
    • Functional role of histatin 1 phosphorylation was not determined
    • No assay for biological activity of the encoded protein was performed
    • Relationship between histatin gene products and antimicrobial or mineral-binding activities was not addressed
  2. 1993 Medium

    Determining the genomic architecture of HTN1 and its evolutionary relationship to STATH showed that despite shared gene structure, accelerated coding-sequence divergence implies distinct functional roles for histatin 1 and statherin.

    Evidence Genomic phage library cloning and nucleotide sequencing of a 39-kb region containing HIS1, HIS2, and STATH, with evolutionary rate analysis

    PMID:8336540

    Open questions at the time
    • Nature of the functional specialization implied by accelerated evolution was not experimentally defined
    • Protein-level functional assays for histatin 1 were not performed
    • Regulatory elements controlling tissue-specific expression were not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct biological function of histatin 1 protein — including its role in antimicrobial defense, wound healing, or enamel pellicle formation — has not been established through mechanistic experimentation in the available primary literature.
  • No loss-of-function or gain-of-function studies exist for HTN1
  • The functional consequence of histatin 1 phosphorylation is unknown
  • No structural model of histatin 1 or its interactions with microbial or mineral targets has been reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005576 extracellular region 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The histatin protein family is encoded by at least two closely related loci (HIS1 and HIS2), with histatin 1 being the primary product of HIS1 and histatin 2 representing the non-phosphorylated form of histatin 1, as determined by cDNA library screening and sequence analysis of human parotid gland cDNA clones. cDNA library screening with synthetic oligonucleotide probes, sequence analysis of 12 cDNA clones Biochemical and biophysical research communications Medium 2719677
1993 The HIS1 gene spans 8.5 kb, contains six exons and five introns, and belongs to a gene family with STATH (statherin) that shows accelerated evolution in protein-coding regions relative to non-coding regions, suggesting functional divergence between histatin and statherin despite shared gene structure. Genomic phage library cloning, nucleotide sequencing of a 39-kb region containing HIS1 and HIS2, sequence alignment and evolutionary analysis Molecular biology and evolution Medium 8336540

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 The maize disease resistance gene Htn1 against northern corn leaf blight encodes a wall-associated receptor-like kinase. Proceedings of the National Academy of Sciences of the United States of America 209 26124097
1983 Repeated DNA sequences upstream from HIS1 also occur at several other co-regulated genes in Saccharomyces cerevisiae. The Journal of biological chemistry 186 6300123
2006 His1 and His2 are distantly related, spindle-shaped haloviruses belonging to the novel virus group, Salterprovirus. Virology 114 16530800
1989 Biological activities of des-His1[Glu9]glucagon amide, a glucagon antagonist. Peptides 112 2560175
1998 His1, an archaeal virus of the Fuselloviridae family that infects Haloarcula hispanica. Journal of virology 82 9765495
1989 Histatins, a family of salivary histidine-rich proteins, are encoded by at least two loci (HIS1 and HIS2). Biochemical and biophysical research communications 77 2719677
2012 Modified coat protein forms the flexible spindle-shaped virion of haloarchaeal virus His1. Environmental microbiology 44 23163639
1993 Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family. Molecular biology and evolution 41 8336540
1995 Cloning of the Candida albicans HIS1 gene by direct complementation of a C. albicans histidine auxotroph using an improved double-ARS shuttle vector. Gene 40 7489899
1994 Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame. Molecular and cellular biology 40 8114708
2022 Linker histone variant HIS1-3 and WRKY1 oppositely regulate salt stress tolerance in Arabidopsis. Plant physiology 39 35474141
1991 His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia. Oncogene 35 1682866
2005 Cloning and disruption of the Pichia pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and their use as auxotrophic markers. Yeast (Chichester, England) 29 15789348
1993 Mechanism of action of des-His1-[Glu9]glucagon amide, a peptide antagonist of the glucagon receptor system. Proceedings of the National Academy of Sciences of the United States of America 22 8383321
1981 Marker effects and the nature of the recombination event at the his1 locus of Saccharomyces cerevisiae. Current genetics 22 24189951
2015 Nickel superoxide dismutase: structural and functional roles of His1 and its H-bonding network. Biochemistry 17 25580509
1998 Topical reversion at the HIS1 locus of Saccharomyces cerevisiae. A tale of three mutants. Genetics 17 9560384
1997 Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues. The American journal of pathology 16 9094986
2003 Sense and antisense transcripts in the histone H1 (HIS-1) locus of Leishmania major. International journal for parasitology 15 12906880
1995 Characterization of Schizosaccharomyces pombe his1 and his5 cDNAs. Yeast (Chichester, England) 11 7732725
1997 Evolutionary conservation of putative functional domains in the human homolog of the murine His-1 gene. Gene 10 9031624
1978 Reversion at the HiS1 locus of yeast. Genetics 10 365679
1979 Regulatory mutants at the his1 locus of yeast. Genetics 9 385447
2021 Exploring Natural Allelic Variations of the β-Triketone Herbicide Resistance Gene HIS1 for Application in indica Rice and Particularly in Two-Line Hybrid Rice. Rice (New York, N.Y.) 8 33415497
2014 Immunocytochemical staining of endogenous nuclear proteins with the HIS-1 anti-poly-histidine monoclonal antibody: a potential source of error in His-tagged protein detection. Acta histochemica 7 24835186
2000 Identification of a cell type-specific silencer in the first exon of the His-1 gene. Journal of cellular biochemistry 6 10653981
1978 Novel interallelic complementation at the his1 locus of yeast. Genetics 6 365680
2001 Molecular characterization and expression study of a histidine auxotrophic mutant (his1-) of Nicotiana plumbaginifolia. Plant molecular biology 5 11289510
2016 Temperature and pH dependence of DNA ejection from archaeal lemon-shaped virus His1. European biophysics journal : EBJ 4 26820561
2004 Ac His1 [D-Phe2, K15, R16, L27] VIP (3-7)/GRF (8-27)--a VPAC1 receptor antagonist--is an inverse agonist on two constitutively active truncated VPAC1 receptors. Peptides 3 15501526
1987 Semisynthetic D-His1,N epsilon-acetimidoglucagon: structure-function relationships. Archives of biochemistry and biophysics 3 2821912
2004 Sequence-specific binding of the Schizosaccharomyces pombe His1 protein to fission yeast telomeric DNA. Chemistry & biodiversity 2 17191912
1980 Genetic Evidence for Interaction between Nonhomologous Proteins in Yeast and a Case of Suppression at the HIS1 Locus. Genetics 2 17249001
2025 Comprehensive characterization and diversity analysis of the HIS1 gene family in rice subpopulations for herbicide resistance. BMC plant biology 1 40122789
2024 Analyzing the response of rice to tefuryltrione herbicide: Haplotype variation and evolutionary dynamics of the HIS1 gene. Environmental research 1 38570131
2019 Fine mapping of a locus presumably involved in hybrid inviability (HIs-1) between flowering cherry cultivar Cerasus × yedoensis 'Somei-yoshino' and its wild relative C. spachiana. Breeding science 1 31988630
2025 Investigating the impact of HIS-1 and HSP-70 genes on drug response and pathology of Leishmania major using antisense oligonucleotides. Antonie van Leeuwenhoek 0 40632305
2024 Evolutionary and synteny analysis of HIS1, BADH2, GBSS1, and GBSS2 in rice: insights for effective introgression breeding strategies. Scientific reports 0 38433262