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P15516

- HIS3_HUMAN

UniProt

P15516 - HIS3_HUMAN

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Protein

Histatin-3

Gene

HTN3

Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Sitei32 – 321Important for candidacidal activity
Metal bindingi34 – 341Zinc
Sitei41 – 411Important for candidacidal activity
Sitei43 – 431Not sulfated
Sitei47 – 471Not sulfated
Sitei49 – 491Not sulfated

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. biomineral tissue development Source: UniProtKB-KW
  2. defense response to bacterium Source: UniProtKB
  3. defense response to fungus Source: UniProtKB-KW
  4. killing of cells of other organism Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Antibiotic, Antimicrobial, Fungicide

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

Metal-binding

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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:5284. HTN3.

Subcellular locationi

Secreted 1 Publication
Note: Secreted by serous acinar and demilune cells.

GO - Cellular componenti

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi31 – 311R → I: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication
Mutagenesisi32 – 321K → T or E: 3-fold reduction in candidacidal activity of His3-(20-43)-peptide. 1 Publication
Mutagenesisi36 – 361K → N: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication
Mutagenesisi38 – 381H → P: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication
Mutagenesisi40 – 401H → L or R: No effect on candidacidal activity of His3-(20-43)-peptide. 1 Publication
Mutagenesisi41 – 411R → G: 10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32. 1 Publication

Organism-specific databases

PharmGKBiPA29547.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 19193 PublicationsAdd
BLAST
Chaini20 – 5132Histatin-3PRO_0000021418Add
BLAST
Peptidei20 – 4425His3-(20-44)-peptidePRO_0000021419Add
BLAST
Peptidei20 – 4324His3-(20-43)-peptidePRO_0000021420Add
BLAST
Peptidei20 – 3213His3-(20-32)-peptidePRO_0000021421Add
BLAST
Peptidei20 – 3112His3-(20-31)-peptidePRO_0000021422Add
BLAST
Peptidei20 – 3011His3-(20-30)-peptidePRO_0000021423Add
BLAST
Peptidei24 – 329His3-(24-32)-peptidePRO_0000021424
Peptidei24 – 318His3-(24-31)-peptidePRO_0000021425
Peptidei24 – 307His3-(24-30)-peptidePRO_0000021426
Peptidei25 – 328His3-(25-32)-peptidePRO_0000021427
Peptidei25 – 306His3-(25-30)-peptidePRO_0000021428
Peptidei26 – 327His3-(26-32)-peptidePRO_0000021429
Peptidei26 – 316His3-(26-31)-peptidePRO_0000021430
Peptidei26 – 305His3-(26-30)-peptidePRO_0000021431
Peptidei31 – 5121His3-(31-51)-peptidePRO_0000021432Add
BLAST
Peptidei31 – 4414His3-(31-44)-peptidePRO_0000021433Add
BLAST
Peptidei31 – 4313His3-(31-43)-peptidePRO_0000021434Add
BLAST
Peptidei32 – 4413His3-(32-44)-peptidePRO_0000021435Add
BLAST
Peptidei32 – 4312His3-(32-43)-peptidePRO_0000021436Add
BLAST
Peptidei33 – 4412His3-(33-44)-peptidePRO_0000021437Add
BLAST
Peptidei33 – 4311His3-(33-43)-peptidePRO_0000021438Add
BLAST
Peptidei34 – 4411His3-(34-44)-peptidePRO_0000021439Add
BLAST
Peptidei34 – 4310His3-(34-43)-peptidePRO_0000021440
Peptidei45 – 517His3-(45-51)-peptidePRO_0000021441
Peptidei47 – 515His3-(47-51)-peptidePRO_0000021442
Peptidei48 – 514His3-(48-51)-peptidePRO_0000021443

Post-translational modificationi

24 proteolytic products are found in saliva.

Keywords - PTMi

Cleavage on pair of basic residues

Proteomic databases

PaxDbiP15516.
PRIDEiP15516.

Expressioni

Gene expression databases

BgeeiP15516.
CleanExiHS_HTN3.
ExpressionAtlasiP15516. baseline.
GenevestigatoriP15516.

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

IntActiP15516. 2 interactions.
MINTiMINT-8415913.
STRINGi9606.ENSP00000370445.

Structurei

3D structure databases

ProteinModelPortaliP15516.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the histatin/statherin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG273986.
GeneTreeiENSGT00390000006107.
HOGENOMiHOG000112905.
HOVERGENiHBG005970.
InParanoidiP15516.
KOiK13913.
OMAiDSHAKRH.
OrthoDBiEOG7TTQBV.
PhylomeDBiP15516.
TreeFamiTF341637.

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411R → Q in histatin-3-2; loss of the proteolytic cleavage site. 1 Publication
Corresponds to variant rs1136511 [ dbSNP | Ensembl ].
VAR_005288
Natural varianti47 – 515Missing in histatin-3-2. 1 Publication
Corresponds to variant rs17147990 [ dbSNP | Ensembl ].
VAR_005289

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
ENST00000616777; ENSP00000479841; ENSG00000205649.
ENST00000621910; ENSP00000478508; ENSG00000205649.
ENST00000622638; ENSP00000481106; ENSG00000205649.
GeneIDi3347.
KEGGihsa:3347.
UCSCiuc003hew.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.654442.

3D structure databases

ProteinModelPortali P15516.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P15516. 2 interactions.
MINTi MINT-8415913.
STRINGi 9606.ENSP00000370445.

Protein family/group databases

TCDBi 1.C.79.1.1. the channel-forming histatin antimicrobial peptide (histatin) family.

Proteomic databases

PaxDbi P15516.
PRIDEi P15516.

Protocols and materials databases

DNASUi 3347.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000526767 ; ENSP00000437158 ; ENSG00000205649 .
ENST00000530128 ; ENSP00000432561 ; ENSG00000205649 .
ENST00000616777 ; ENSP00000479841 ; ENSG00000205649 .
ENST00000621910 ; ENSP00000478508 ; ENSG00000205649 .
ENST00000622638 ; ENSP00000481106 ; ENSG00000205649 .
GeneIDi 3347.
KEGGi hsa:3347.
UCSCi uc003hew.2. human.

Organism-specific databases

CTDi 3347.
GeneCardsi GC04P070894.
HGNCi HGNC:5284. HTN3.
MIMi 142702. gene.
neXtProti NX_P15516.
PharmGKBi PA29547.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG273986.
GeneTreei ENSGT00390000006107.
HOGENOMi HOG000112905.
HOVERGENi HBG005970.
InParanoidi P15516.
KOi K13913.
OMAi DSHAKRH.
OrthoDBi EOG7TTQBV.
PhylomeDBi P15516.
TreeFami TF341637.

Miscellaneous databases

ChiTaRSi HTN3. human.
GeneWikii HTN3.
GenomeRNAii 3347.
NextBioi 13240.
PROi P15516.
SOURCEi Search...

Gene expression databases

Bgeei P15516.
CleanExi HS_HTN3.
ExpressionAtlasi P15516. baseline.
Genevestigatori P15516.

Family and domain databases

ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Histatins, a family of salivary histidine-rich proteins, are encoded by at least two loci (HIS1 and HIS2)."
    Sabatini L.M., Azen E.A.
    Biochem. Biophys. Res. Commun. 160:495-502(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Human submandibular gland statherin and basic histidine-rich peptide are encoded by highly abundant mRNA's derived from a common ancestral sequence."
    Dickinson D.P., Ridall A.L., Levine M.J.
    Biochem. Biophys. Res. Commun. 149:784-790(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family."
    Chen Z.W.
    Mol. Biol. Evol. 10:497-511(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Skeletal muscle and Thyroid.
  6. "Two coding change mutations in the HIS2(2) allele characterize the salivary histatin 3-2 protein variant."
    Sabatini L.M., Azen E.A.
    Hum. Mutat. 4:12-19(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-51, VARIANTS HISTATIN-3-2 GLN-41 AND 47-TYR--ASN-51 DEL.
    Tissue: Saliva.
  7. "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. 263:7472-7477(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 20-51.
    Tissue: Parotid gland.
  8. "Rapid purification and characterization of histatins (histidine-rich polypeptides) from human whole saliva."
    Sugiyama K., Ogino T., Ogata K.
    Arch. Oral Biol. 35:415-419(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 20-42.
    Tissue: Saliva.
  9. "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. 279:41436-41443(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 20-32, IDENTIFICATION BY MASS SPECTROMETRY OF 24 PEPTIDE FRAGMENTS.
    Tissue: Saliva.
  10. "Candidacidal activity of recombinant human salivary histatin-5 and variants."
    Tsai H., Raj P.A., Bobek L.A.
    Infect. Immun. 64:5000-5007(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ARG-31; LYS-32; LYS-36; HIS-38; HIS-40 AND ARG-41.
  11. "Zinc and copper bind to unique sites of histatin 5."
    Grogan J., McKnight C.J., Troxler R.F., Oppenheim F.G.
    FEBS Lett. 491:76-80(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: ZINC-BINDING SITE.
  12. "Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease."
    Gusman H., Travis J., Helmerhorst E.J., Potempa J., Troxler R.F., Oppenheim F.G.
    Infect. Immun. 69:1402-1408(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Candida albicans Ssa1/2p is the cell envelope binding protein for human salivary histatin 5."
    Li X.S., Reddy M.S., Baev D., Edgerton M.
    J. Biol. Chem. 278:28553-28561(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SSA1 AND SSA2.
  14. "Immunocytochemical localization of histatins in human salivary glands."
    Ahmad M., Piludu M., Oppenheim F.G., Helmerhorst E.J., Hand A.R.
    J. Histochem. Cytochem. 52:361-370(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  15. "Tyrosine polysulfation of human salivary histatin 1. A post-translational modification specific of the submandibular gland."
    Cabras T., Fanali C., Monteiro J.A., Amado F., Inzitari R., Desiderio C., Scarano E., Giardina B., Castagnola M., Messana I.
    J. Proteome Res. 6:2472-2480(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF SULFATION AT TYR-43; TYR-47 AND TYR-49, IDENTIFICATION BY MASS SPECTROMETRY.
  16. Cited for: PEPTIDE NOMENCLATURE.

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: October 29, 2014
This is version 132 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

External Data

Dasty 3