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Protein

Histatin-3

Gene

HTN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Sites

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Antibiotic, Antimicrobial, Fungicide

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

Metal-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

HGNCiHGNC:5284. HTN3.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
Complete GO annotation...

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.
ENSG00000282967.
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
Sitei47Not sulfated1
Sitei49Not sulfated1

Keywords - PTMi

Cleavage on pair of basic residues

Proteomic databases

PaxDbiP15516.
PeptideAtlasiP15516.
PRIDEiP15516.

Expressioni

Gene expression databases

BgeeiENSG00000205649.
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 a different organism.

Protein-protein interaction databases

BioGridi109579. 1 interactor.
IntActiP15516. 3 interactors.
MINTiMINT-8415913.
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.
OMAiKRHHGYK.
OrthoDBiEOG091G16XM.
PhylomeDBiP15516.
TreeFamiTF341637.

Family and domain databases

InterProiIPR030771. Histatin-3.
IPR030773. Histatin/statherin.
[Graphical view]
PANTHERiPTHR15057. PTHR15057. 1 hit.
PTHR15057:SF1. PTHR15057:SF1. 1 hit.

Sequencei

Sequence statusi: Complete.

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

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

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 rs1136511dbSNPEnsembl.1
Natural variantiVAR_00528947 – 51Missing in histatin-3-2. 1 PublicationCorresponds to variant rs17147990dbSNPEnsembl.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

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. 1 interactor.
IntActiP15516. 3 interactors.
MINTiMINT-8415913.
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.

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.
GeneCardsiHTN3.
HGNCiHGNC:5284. HTN3.
HPAiCAB073541.
MIMi142702. gene.
neXtProtiNX_P15516.
OpenTargetsiENSG00000205649.
ENSG00000282967.
PharmGKBiPA29547.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-6803157. Antimicrobial peptides.

Miscellaneous databases

ChiTaRSiHTN3. human.
GeneWikiiHTN3.
GenomeRNAii3347.
PROiP15516.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000205649.
CleanExiHS_HTN3.
ExpressionAtlasiP15516. baseline and differential.
GenevisibleiP15516. HS.

Family and domain databases

InterProiIPR030771. Histatin-3.
IPR030773. Histatin/statherin.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: November 30, 2016
This is version 146 of the entry and version 2 of the sequence. [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

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.