UniProtKB - P15516 (HIS3_HUMAN)
Protein
Histatin-3
Gene
HTN3
Organism
Homo sapiens (Human)
Status
Functioni
Histatins are salivary proteins that are considered to be major precursors of the protective proteinaceous structure on tooth surfaces (enamel pellicle). In addition, histatins exhibit antibacterial and antifungal activities. His3-(20-43)-peptide (histatin-5) is especially effective against C.albicans and C.neoformans, and inhibits Lys-gingipain and Arg-gingipain (rgpB) from P.gingivalis. In addition, His3-(20-43)-peptide is a potent inhibitor of metalloproteinases MMP2 and MMP9.2 Publications
Miscellaneous
The recommended nomenclature of salivary peptides follows published guidelines (PubMed:20973643). In agreement with the authors, it has been decided to indicate the boundaries of the peptides according to the positions within the precursor, and not in the mature protein, as has formerly been proposed.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 32 | Important for candidacidal activity | 1 | |
Metal bindingi | 34 | Zinc | 1 | |
Sitei | 41 | Important for candidacidal activity | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
- antimicrobial humoral response Source: Reactome
- biomineral tissue development Source: UniProtKB-KW
- defense response to bacterium Source: UniProtKB
- defense response to fungus Source: UniProtKB-KW
- killing of cells of other organism Source: UniProtKB
Keywordsi
Molecular function | Antibiotic, Antimicrobial, Fungicide |
Biological process | Biomineralization |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P15516 |
Reactomei | R-HSA-6803157, Antimicrobial peptides |
Protein family/group databases
TCDBi | 1.C.79.1.1, the channel-forming histatin antimicrobial peptide (histatin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Histatin-3Alternative name(s): Basic histidine-rich protein Short name: Hst Histidine-rich protein 3 PB Cleaved into the following 26 chains: Alternative name(s): His3-(1-25)-peptide Short name: His3 1/25 Histatin-3 1/25 Histatin-6 Alternative name(s): His3-(1-24)-peptide Short name: His3 1/24 Histatin-3 1/24 Histatin-5 Alternative name(s): His3-(1-13)-peptide Short name: His3 1/13 Histatin-3 1/13 Alternative name(s): His3-(1-12)-peptide Short name: His3 1/12 Histatin-3 1/12 Alternative name(s): His3-(1-11)-peptide Short name: His3 1/11 Histatin-3 1/11 Alternative name(s): His3-(5-13)-peptide Short name: His3 5/13 Histatin-3 5/13 Alternative name(s): His3-(5-12)-peptide Short name: His3 5/12 Histatin-11 Histatin-3 5/12 Alternative name(s): His3-(5-11)-peptide Short name: His3 5/11 Histatin-12 Histatin-3 5/11 Alternative name(s): His3-(6-13)-peptide Short name: His3 6/13 Histatin-3 6/13 Alternative name(s): His3-(6-11)-peptide Short name: His3 6/11 Histatin-3 6/11 Alternative name(s): His3-(7-13)-peptide Short name: His3 7/13 Histatin-3 7/13 Alternative name(s): His3-(7-12)-peptide Short name: His3 7/12 Histatin-3 7/12 Alternative name(s): His3-(7-11)-peptide Short name: His3 7/11 Histatin-3 7/11 Alternative name(s): His3-(12-32)-peptide Short name: His3 12/32 Histatin-3 12/32 Histatin-4 Alternative name(s): His3-(12-25)-peptide Short name: His3 12/25 Histatin-3 12/25 Histatin-9 Alternative name(s): His3-(12-24)-peptide Short name: His3 12/24 Histatin-3 12/24 Histatin-7 Alternative name(s): His3-(13-25)-peptide Short name: His3 13/25 Histatin-10 Histatin-3 13/25 Alternative name(s): His3-(13-24)-peptide Short name: His3 13/24 Histatin-3 13/24 Histatin-8 Alternative name(s): His3-(14-25)-peptide Short name: His3 14/25 Histatin-3 14/25 Alternative name(s): His3-(14-24)-peptide Short name: His3 14/24 Histatin-3 14/24 Alternative name(s): His3-(15-25)-peptide Short name: His3 15/25 Histatin-3 15/25 Alternative name(s): His3-(15-24)-peptide Short name: His3 15/24 Histatin-3 15/24 Alternative name(s): His3-(26-32)-peptide Short name: His3 26/32 Histatin-3 26/32 Alternative name(s): His3-(28-32)-peptide Short name: His3 28/32 Histatin-3 28/32 Alternative name(s): His3-(29-32)-peptide Short name: His3 29/32 Histatin-3 29/32 |
Gene namesi | Name:HTN3 Synonyms:HIS2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5284, HTN3 |
MIMi | 142702, gene |
neXtProti | NX_P15516 |
VEuPathDBi | HostDB:ENSG00000205649.7 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Note: Secreted by serous acinar and demilune cells.
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 31 | R → I: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication | 1 | |
Mutagenesisi | 32 | K → T or E: 3-fold reduction in candidacidal activity of His3-(20-43)-peptide. 1 Publication | 1 | |
Mutagenesisi | 36 | K → N: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication | 1 | |
Mutagenesisi | 38 | H → P: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication | 1 | |
Mutagenesisi | 40 | H → L or R: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication | 1 | |
Mutagenesisi | 41 | R → G: 10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3347 |
OpenTargetsi | ENSG00000205649 |
PharmGKBi | PA29547 |
Miscellaneous databases
Pharosi | P15516, Tbio |
Genetic variation databases
BioMutai | HTN3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | 3 PublicationsAdd BLAST | 19 | |
ChainiPRO_0000021418 | 20 – 51 | Histatin-3Add BLAST | 32 | |
PeptideiPRO_0000021419 | 20 – 44 | His3-(20-44)-peptideAdd BLAST | 25 | |
PeptideiPRO_0000021420 | 20 – 43 | His3-(20-43)-peptideAdd BLAST | 24 | |
PeptideiPRO_0000021421 | 20 – 32 | His3-(20-32)-peptideAdd BLAST | 13 | |
PeptideiPRO_0000021422 | 20 – 31 | His3-(20-31)-peptideAdd BLAST | 12 | |
PeptideiPRO_0000021423 | 20 – 30 | His3-(20-30)-peptideAdd BLAST | 11 | |
PeptideiPRO_0000021424 | 24 – 32 | His3-(24-32)-peptide | 9 | |
PeptideiPRO_0000021425 | 24 – 31 | His3-(24-31)-peptide | 8 | |
PeptideiPRO_0000021426 | 24 – 30 | His3-(24-30)-peptide | 7 | |
PeptideiPRO_0000021427 | 25 – 32 | His3-(25-32)-peptide | 8 | |
PeptideiPRO_0000021428 | 25 – 30 | His3-(25-30)-peptide | 6 | |
PeptideiPRO_0000021429 | 26 – 32 | His3-(26-32)-peptide | 7 | |
PeptideiPRO_0000021430 | 26 – 31 | His3-(26-31)-peptide | 6 | |
PeptideiPRO_0000021431 | 26 – 30 | His3-(26-30)-peptide | 5 | |
PeptideiPRO_0000021432 | 31 – 51 | His3-(31-51)-peptideAdd BLAST | 21 | |
PeptideiPRO_0000021433 | 31 – 44 | His3-(31-44)-peptideAdd BLAST | 14 | |
PeptideiPRO_0000021434 | 31 – 43 | His3-(31-43)-peptideAdd BLAST | 13 | |
PeptideiPRO_0000021435 | 32 – 44 | His3-(32-44)-peptideAdd BLAST | 13 | |
PeptideiPRO_0000021436 | 32 – 43 | His3-(32-43)-peptideAdd BLAST | 12 | |
PeptideiPRO_0000021437 | 33 – 44 | His3-(33-44)-peptideAdd BLAST | 12 | |
PeptideiPRO_0000021438 | 33 – 43 | His3-(33-43)-peptideAdd BLAST | 11 | |
PeptideiPRO_0000021439 | 34 – 44 | His3-(34-44)-peptideAdd BLAST | 11 | |
PeptideiPRO_0000021440 | 34 – 43 | His3-(34-43)-peptide | 10 | |
PeptideiPRO_0000021441 | 45 – 51 | His3-(45-51)-peptide | 7 | |
PeptideiPRO_0000021442 | 47 – 51 | His3-(47-51)-peptide | 5 | |
PeptideiPRO_0000021443 | 48 – 51 | His3-(48-51)-peptide | 4 |
Post-translational modificationi
24 proteolytic products are found in saliva.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 43 | Not sulfated1 Publication | 1 | |
Sitei | 47 | Not sulfated1 Publication | 1 | |
Sitei | 49 | Not sulfated1 Publication | 1 |
Keywords - PTMi
Cleavage on pair of basic residuesProteomic databases
MassIVEi | P15516 |
PaxDbi | P15516 |
PeptideAtlasi | P15516 |
PRIDEi | P15516 |
ProteomicsDBi | 53166 |
Expressioni
Gene expression databases
Bgeei | ENSG00000205649, Expressed in saliva-secreting gland and 67 other tissues |
ExpressionAtlasi | P15516, baseline and differential |
Genevisiblei | P15516, HS |
Organism-specific databases
HPAi | ENSG00000205649, Tissue enriched (salivary) |
Interactioni
Subunit structurei
His3-(20-43)-peptide is a homodimer. Histatin-3 and His3-(20-43)-peptide interact with yeast SSA1 and SSA2 proteins.
Binary interactionsi
Hide detailsP15516
With | #Exp. | IntAct |
---|---|---|
DNAJB11 [Q9UBS4] | 3 | EBI-738783,EBI-713113 |
rgpB [P95493] from Porphyromonas gingivalis (strain ATCC BAA-308 / W83). | 7 | EBI-738783,EBI-8505881 |
Protein-protein interaction databases
BioGRIDi | 109579, 32 interactors |
IntActi | P15516, 4 interactors |
MINTi | P15516 |
STRINGi | 9606.ENSP00000432561 |
Miscellaneous databases
RNActi | P15516, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the histatin/statherin family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502TEIC, Eukaryota |
GeneTreei | ENSGT00940000164572 |
InParanoidi | P15516 |
OMAi | DSHEEKH |
OrthoDBi | 1623335at2759 |
PhylomeDBi | P15516 |
TreeFami | TF341637 |
Family and domain databases
DisProti | DP02206 |
InterProi | View protein in InterPro IPR030774, Histatin-3 IPR030773, Histatin/statherin |
PANTHERi | PTHR15057, PTHR15057, 1 hit PTHR15057:SF1, PTHR15057:SF1, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P15516-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKFFVFALIL ALMLSMTGAD SHAKRHHGYK RKFHEKHHSH RGYRSNYLYD
N
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketX6RAH8 | X6RAH8_HUMAN | Histatin-3 | HTN3 | 41 | Annotation score: |
Polymorphismi
There are two alleles of HTN3, HIS21 (shown here) and HIS22 that codes for the variant histatin-3-2 found primarily and in high frequencies in black populations.1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_005288 | 41 | R → Q in histatin-3-2; loss of the proteolytic cleavage site. 1 PublicationCorresponds to variant dbSNP:rs1136511EnsemblClinVar. | 1 | |
Natural variantiVAR_005289 | 47 – 51 | Missing in histatin-3-2. 1 PublicationCorresponds to variant dbSNP:rs17147990Ensembl. | 5 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M26665 mRNA Translation: AAA58646.1 M18372 mRNA Translation: AAA51830.1 L05514, L05513 Genomic DNA Translation: AAA02746.1 BC009791 mRNA Translation: AAH09791.1 BC095438 mRNA Translation: AAH95438.1 S74382 Genomic DNA Translation: AAB32411.1 |
CCDSi | CCDS33999.1 |
PIRi | B32541 |
RefSeqi | NP_000191.1, NM_000200.2 |
Genome annotation databases
Ensembli | ENST00000530128; ENSP00000432561; ENSG00000205649 ENST00000635585; ENSP00000489520; ENSG00000282967 ENST00000672568; ENSP00000500810; ENSG00000282967 ENST00000673563; ENSP00000500623; ENSG00000205649 ENST00000677679; ENSP00000504141; ENSG00000282967 |
GeneIDi | 3347 |
KEGGi | hsa:3347 |
UCSCi | uc003hew.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M26665 mRNA Translation: AAA58646.1 M18372 mRNA Translation: AAA51830.1 L05514, L05513 Genomic DNA Translation: AAA02746.1 BC009791 mRNA Translation: AAH09791.1 BC095438 mRNA Translation: AAH95438.1 S74382 Genomic DNA Translation: AAB32411.1 |
CCDSi | CCDS33999.1 |
PIRi | B32541 |
RefSeqi | NP_000191.1, NM_000200.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 109579, 32 interactors |
IntActi | P15516, 4 interactors |
MINTi | P15516 |
STRINGi | 9606.ENSP00000432561 |
Protein family/group databases
TCDBi | 1.C.79.1.1, the channel-forming histatin antimicrobial peptide (histatin) family |
Genetic variation databases
BioMutai | HTN3 |
Proteomic databases
MassIVEi | P15516 |
PaxDbi | P15516 |
PeptideAtlasi | P15516 |
PRIDEi | P15516 |
ProteomicsDBi | 53166 |
Protocols and materials databases
Antibodypediai | 24280, 11 antibodies |
DNASUi | 3347 |
Genome annotation databases
Ensembli | ENST00000530128; ENSP00000432561; ENSG00000205649 ENST00000635585; ENSP00000489520; ENSG00000282967 ENST00000672568; ENSP00000500810; ENSG00000282967 ENST00000673563; ENSP00000500623; ENSG00000205649 ENST00000677679; ENSP00000504141; ENSG00000282967 |
GeneIDi | 3347 |
KEGGi | hsa:3347 |
UCSCi | uc003hew.2, human |
Organism-specific databases
CTDi | 3347 |
DisGeNETi | 3347 |
GeneCardsi | HTN3 |
HGNCi | HGNC:5284, HTN3 |
HPAi | ENSG00000205649, Tissue enriched (salivary) |
MIMi | 142702, gene |
neXtProti | NX_P15516 |
OpenTargetsi | ENSG00000205649 |
PharmGKBi | PA29547 |
VEuPathDBi | HostDB:ENSG00000205649.7 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502TEIC, Eukaryota |
GeneTreei | ENSGT00940000164572 |
InParanoidi | P15516 |
OMAi | DSHEEKH |
OrthoDBi | 1623335at2759 |
PhylomeDBi | P15516 |
TreeFami | TF341637 |
Enzyme and pathway databases
PathwayCommonsi | P15516 |
Reactomei | R-HSA-6803157, Antimicrobial peptides |
Miscellaneous databases
BioGRID-ORCSi | 3347, 0 hits in 456 CRISPR screens |
ChiTaRSi | HTN3, human |
GeneWikii | HTN3 |
GenomeRNAii | 3347 |
Pharosi | P15516, Tbio |
PROi | PR:P15516 |
RNActi | P15516, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000205649, Expressed in saliva-secreting gland and 67 other tissues |
ExpressionAtlasi | P15516, baseline and differential |
Genevisiblei | P15516, HS |
Family and domain databases
DisProti | DP02206 |
InterProi | View protein in InterPro IPR030774, Histatin-3 IPR030773, Histatin/statherin |
PANTHERi | PTHR15057, PTHR15057, 1 hit PTHR15057:SF1, PTHR15057:SF1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HIS3_HUMAN | |
Accessioni | P15516Primary (citable) accession number: P15516 Secondary accession number(s): Q16243, Q502Z1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1990 |
Last sequence update: | February 1, 1991 | |
Last modified: | April 7, 2021 | |
This is version 175 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families