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Protein

Histatin-3

Gene

HTN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei32Important for candidacidal activity1
Metal bindingi34Zinc1
Sitei41Important for candidacidal activity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAntibiotic, Antimicrobial, Fungicide
Biological processBiomineralization
LigandMetal-binding

Enzyme and pathway databases

ReactomeiR-HSA-6803157 Antimicrobial peptides

Protein family/group databases

TCDBi1.C.79.1.1 the channel-forming histatin antimicrobial peptide (histatin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Histatin-3
Alternative name(s):
Basic histidine-rich protein
Short name:
Hst
Histidine-rich protein 3
PB
Cleaved into the following 26 chains:
His3-(20-44)-peptide
Short name:
His3 20/44
Alternative name(s):
His3-(1-25)-peptide
Short name:
His3 1/25
Histatin-3 1/25
Histatin-6
His3-(20-43)-peptide
Short name:
His3 20/43
Alternative name(s):
His3-(1-24)-peptide
Short name:
His3 1/24
Histatin-3 1/24
Histatin-5
His3-(20-32)-peptide
Short name:
His3 20/32
Alternative name(s):
His3-(1-13)-peptide
Short name:
His3 1/13
Histatin-3 1/13
His3-(20-31)-peptide
Short name:
His3 20/31
Alternative name(s):
His3-(1-12)-peptide
Short name:
His3 1/12
Histatin-3 1/12
His3-(20-30)-peptide
Short name:
His3 20/30
Alternative name(s):
His3-(1-11)-peptide
Short name:
His3 1/11
Histatin-3 1/11
His3-(24-32)-peptide
Short name:
His3 24/32
Alternative name(s):
His3-(5-13)-peptide
Short name:
His3 5/13
Histatin-3 5/13
His3-(24-31)-peptide
Short name:
His3 24/31
Alternative name(s):
His3-(5-12)-peptide
Short name:
His3 5/12
Histatin-11
Histatin-3 5/12
His3-(24-30)-peptide
Short name:
His3 24/30
Alternative name(s):
His3-(5-11)-peptide
Short name:
His3 5/11
Histatin-12
Histatin-3 5/11
His3-(25-32)-peptide
Short name:
His3 25/32
Alternative name(s):
His3-(6-13)-peptide
Short name:
His3 6/13
Histatin-3 6/13
His3-(25-30)-peptide
Short name:
His3 25/30
Alternative name(s):
His3-(6-11)-peptide
Short name:
His3 6/11
Histatin-3 6/11
His3-(26-32)-peptide
Short name:
His3 26/32
Alternative name(s):
His3-(7-13)-peptide
Short name:
His3 7/13
Histatin-3 7/13
His3-(26-31)-peptide
Short name:
His3 26/31
Alternative name(s):
His3-(7-12)-peptide
Short name:
His3 7/12
Histatin-3 7/12
His3-(26-30)-peptide
Short name:
His3 26/30
Alternative name(s):
His3-(7-11)-peptide
Short name:
His3 7/11
Histatin-3 7/11
His3-(31-51)-peptide
Short name:
His3 31/51
Alternative name(s):
His3-(12-32)-peptide
Short name:
His3 12/32
Histatin-3 12/32
Histatin-4
His3-(31-44)-peptide
Short name:
His3 31/44
Alternative name(s):
His3-(12-25)-peptide
Short name:
His3 12/25
Histatin-3 12/25
Histatin-9
His3-(31-43)-peptide
Short name:
His3 31/43
Alternative name(s):
His3-(12-24)-peptide
Short name:
His3 12/24
Histatin-3 12/24
Histatin-7
His3-(32-44)-peptide
Short name:
His3 32/44
Alternative name(s):
His3-(13-25)-peptide
Short name:
His3 13/25
Histatin-10
Histatin-3 13/25
His3-(32-43)-peptide
Short name:
His3 32-43
Alternative name(s):
His3-(13-24)-peptide
Short name:
His3 13/24
Histatin-3 13/24
Histatin-8
His3-(33-44)-peptide
Short name:
His3 33/44
Alternative name(s):
His3-(14-25)-peptide
Short name:
His3 14/25
Histatin-3 14/25
His3-(33-43)-peptide
Short name:
His3 33/43
Alternative name(s):
His3-(14-24)-peptide
Short name:
His3 14/24
Histatin-3 14/24
His3-(34-44)-peptide
Short name:
His3 34/44
Alternative name(s):
His3-(15-25)-peptide
Short name:
His3 15/25
Histatin-3 15/25
His3-(34-43)-peptide
Short name:
His3 34/43
Alternative name(s):
His3-(15-24)-peptide
Short name:
His3 15/24
Histatin-3 15/24
His3-(45-51)-peptide
Short name:
His3 45/51
Alternative name(s):
His3-(26-32)-peptide
Short name:
His3 26/32
Histatin-3 26/32
His3-(47-51)-peptide
Short name:
His3 47/51
Alternative name(s):
His3-(28-32)-peptide
Short name:
His3 28/32
Histatin-3 28/32
His3-(48-51)-peptide
Short name:
His3 48/51
Alternative name(s):
His3-(29-32)-peptide
Short name:
His3 29/32
Histatin-3 29/32
Gene namesi
Name:HTN3
Synonyms:HIS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000205649.7
HGNCiHGNC:5284 HTN3
MIMi142702 gene
neXtProtiNX_P15516

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi31R → I: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication1
Mutagenesisi32K → T or E: 3-fold reduction in candidacidal activity of His3-(20-43)-peptide. 1 Publication1
Mutagenesisi36K → N: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication1
Mutagenesisi38H → P: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication1
Mutagenesisi40H → L or R: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication1
Mutagenesisi41R → G: 10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32. 1 Publication1

Organism-specific databases

DisGeNETi3347
OpenTargetsiENSG00000205649
PharmGKBiPA29547

Polymorphism and mutation databases

BioMutaiHTN3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 193 PublicationsAdd BLAST19
ChainiPRO_000002141820 – 51Histatin-3Add BLAST32
PeptideiPRO_000002141920 – 44His3-(20-44)-peptideAdd BLAST25
PeptideiPRO_000002142020 – 43His3-(20-43)-peptideAdd BLAST24
PeptideiPRO_000002142120 – 32His3-(20-32)-peptideAdd BLAST13
PeptideiPRO_000002142220 – 31His3-(20-31)-peptideAdd BLAST12
PeptideiPRO_000002142320 – 30His3-(20-30)-peptideAdd BLAST11
PeptideiPRO_000002142424 – 32His3-(24-32)-peptide9
PeptideiPRO_000002142524 – 31His3-(24-31)-peptide8
PeptideiPRO_000002142624 – 30His3-(24-30)-peptide7
PeptideiPRO_000002142725 – 32His3-(25-32)-peptide8
PeptideiPRO_000002142825 – 30His3-(25-30)-peptide6
PeptideiPRO_000002142926 – 32His3-(26-32)-peptide7
PeptideiPRO_000002143026 – 31His3-(26-31)-peptide6
PeptideiPRO_000002143126 – 30His3-(26-30)-peptide5
PeptideiPRO_000002143231 – 51His3-(31-51)-peptideAdd BLAST21
PeptideiPRO_000002143331 – 44His3-(31-44)-peptideAdd BLAST14
PeptideiPRO_000002143431 – 43His3-(31-43)-peptideAdd BLAST13
PeptideiPRO_000002143532 – 44His3-(32-44)-peptideAdd BLAST13
PeptideiPRO_000002143632 – 43His3-(32-43)-peptideAdd BLAST12
PeptideiPRO_000002143733 – 44His3-(33-44)-peptideAdd BLAST12
PeptideiPRO_000002143833 – 43His3-(33-43)-peptideAdd BLAST11
PeptideiPRO_000002143934 – 44His3-(34-44)-peptideAdd BLAST11
PeptideiPRO_000002144034 – 43His3-(34-43)-peptide10
PeptideiPRO_000002144145 – 51His3-(45-51)-peptide7
PeptideiPRO_000002144247 – 51His3-(47-51)-peptide5
PeptideiPRO_000002144348 – 51His3-(48-51)-peptide4

Post-translational modificationi

24 proteolytic products are found in saliva.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei43Not sulfated1 Publication1
Sitei47Not sulfated1 Publication1
Sitei49Not sulfated1 Publication1

Keywords - PTMi

Cleavage on pair of basic residues

Proteomic databases

PaxDbiP15516
PeptideAtlasiP15516
PRIDEiP15516
ProteomicsDBi53166

Expressioni

Gene expression databases

BgeeiENSG00000205649 Expressed in 44 organ(s), highest expression level in saliva-secreting gland
CleanExiHS_HTN3
ExpressionAtlasiP15516 baseline and differential
GenevisibleiP15516 HS

Organism-specific databases

HPAiCAB073541

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

WithEntry#Exp.IntActNotes
rgpBP954937EBI-738783,EBI-8505881From Porphyromonas gingivalis (strain ATCC BAA-308 / W83).

Protein-protein interaction databases

BioGridi109579, 30 interactors
IntActiP15516, 3 interactors
MINTiP15516
STRINGi9606.ENSP00000432561

Structurei

3D structure databases

ProteinModelPortaliP15516
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the histatin/statherin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410KC9Z Eukaryota
ENOG4110P6H LUCA
GeneTreeiENSGT00390000006107
HOGENOMiHOG000112905
HOVERGENiHBG005970
InParanoidiP15516
KOiK13913
OMAiDSHAKRH
OrthoDBiEOG091G16XM
PhylomeDBiP15516
TreeFamiTF341637

Family and domain databases

InterProiView protein in InterPro
IPR030774 Histatin-1/3
IPR030773 Histatin/statherin
PANTHERiPTHR15057 PTHR15057, 1 hit
PTHR15057:SF1 PTHR15057:SF1, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P15516-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKFFVFALIL ALMLSMTGAD SHAKRHHGYK RKFHEKHHSH RGYRSNYLYD

N
Length:51
Mass (Da):6,149
Last modified:February 1, 1991 - v2
Checksum:iAFCCB4B32083FD65
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
X6RAH8X6RAH8_HUMAN
Histatin-3
HTN3
41Annotation 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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00528841R → Q in histatin-3-2; loss of the proteolytic cleavage site. 1 PublicationCorresponds to variant dbSNP:rs1136511EnsemblClinVar.1
Natural variantiVAR_00528947 – 51Missing 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
CCDSiCCDS33999.1
PIRiB32541
RefSeqiNP_000191.1, NM_000200.2
UniGeneiHs.654442

Genome annotation databases

EnsembliENST00000526767; ENSP00000437158; ENSG00000205649
ENST00000530128; ENSP00000432561; ENSG00000205649
ENST00000634949; ENSP00000489290; ENSG00000282967
ENST00000635585; ENSP00000489520; ENSG00000282967
GeneIDi3347
KEGGihsa:3347
UCSCiuc003hew.2 human

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS33999.1
PIRiB32541
RefSeqiNP_000191.1, NM_000200.2
UniGeneiHs.654442

3D structure databases

ProteinModelPortaliP15516
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109579, 30 interactors
IntActiP15516, 3 interactors
MINTiP15516
STRINGi9606.ENSP00000432561

Protein family/group databases

TCDBi1.C.79.1.1 the channel-forming histatin antimicrobial peptide (histatin) family

Polymorphism and mutation databases

BioMutaiHTN3

Proteomic databases

PaxDbiP15516
PeptideAtlasiP15516
PRIDEiP15516
ProteomicsDBi53166

Protocols and materials databases

DNASUi3347
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000526767; ENSP00000437158; ENSG00000205649
ENST00000530128; ENSP00000432561; ENSG00000205649
ENST00000634949; ENSP00000489290; ENSG00000282967
ENST00000635585; ENSP00000489520; ENSG00000282967
GeneIDi3347
KEGGihsa:3347
UCSCiuc003hew.2 human

Organism-specific databases

CTDi3347
DisGeNETi3347
EuPathDBiHostDB:ENSG00000205649.7
GeneCardsiHTN3
HGNCiHGNC:5284 HTN3
HPAiCAB073541
MIMi142702 gene
neXtProtiNX_P15516
OpenTargetsiENSG00000205649
PharmGKBiPA29547
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410KC9Z Eukaryota
ENOG4110P6H LUCA
GeneTreeiENSGT00390000006107
HOGENOMiHOG000112905
HOVERGENiHBG005970
InParanoidiP15516
KOiK13913
OMAiDSHAKRH
OrthoDBiEOG091G16XM
PhylomeDBiP15516
TreeFamiTF341637

Enzyme and pathway databases

ReactomeiR-HSA-6803157 Antimicrobial peptides

Miscellaneous databases

ChiTaRSiHTN3 human
GeneWikiiHTN3
GenomeRNAii3347
PROiPR:P15516
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000205649 Expressed in 44 organ(s), highest expression level in saliva-secreting gland
CleanExiHS_HTN3
ExpressionAtlasiP15516 baseline and differential
GenevisibleiP15516 HS

Family and domain databases

InterProiView protein in InterPro
IPR030774 Histatin-1/3
IPR030773 Histatin/statherin
PANTHERiPTHR15057 PTHR15057, 1 hit
PTHR15057:SF1 PTHR15057:SF1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHIS3_HUMAN
AccessioniPrimary (citable) accession number: P15516
Secondary accession number(s): Q16243, Q502Z1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: November 7, 2018
This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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