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P15516 (HIS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histatin-3
Alternative name(s):
Basic histidine-rich protein
Short name=Hst
Histidine-rich protein 3
PB

Cleaved into the following 26 chains:

  1. Histatin-3
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  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
  25. 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
  26. 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 names
Name:HTN3
Synonyms:HIS2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length51 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.12

Subunit structure

His3-(20-43)-peptide is a homodimer. Histatin-3 and His3-(20-43)-peptide interact with yeast SSA1 and SSA2 proteins.

Subcellular location

Secreted. Note: Secreted by serous acinar and demilune cells. Ref.14

Post-translational modification

24 proteolytic products are found in saliva.

Polymorphism

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.

Miscellaneous

The recommended nomenclature of salivary peptides follows published guidelines (Ref.16). 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.

Sequence similarities

Belongs to the histatin/statherin family.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

rgpBP954937EBI-738783,EBI-8505881From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.7 Ref.8 Ref.9
Chain20 – 5132Histatin-3
PRO_0000021418
Peptide20 – 4425His3-(20-44)-peptide
PRO_0000021419
Peptide20 – 4324His3-(20-43)-peptide
PRO_0000021420
Peptide20 – 3213His3-(20-32)-peptide Ref.9
PRO_0000021421
Peptide20 – 3112His3-(20-31)-peptide
PRO_0000021422
Peptide20 – 3011His3-(20-30)-peptide
PRO_0000021423
Peptide24 – 329His3-(24-32)-peptide
PRO_0000021424
Peptide24 – 318His3-(24-31)-peptide
PRO_0000021425
Peptide24 – 307His3-(24-30)-peptide
PRO_0000021426
Peptide25 – 328His3-(25-32)-peptide
PRO_0000021427
Peptide25 – 306His3-(25-30)-peptide
PRO_0000021428
Peptide26 – 327His3-(26-32)-peptide
PRO_0000021429
Peptide26 – 316His3-(26-31)-peptide
PRO_0000021430
Peptide26 – 305His3-(26-30)-peptide
PRO_0000021431
Peptide31 – 5121His3-(31-51)-peptide
PRO_0000021432
Peptide31 – 4414His3-(31-44)-peptide
PRO_0000021433
Peptide31 – 4313His3-(31-43)-peptide
PRO_0000021434
Peptide32 – 4413His3-(32-44)-peptide
PRO_0000021435
Peptide32 – 4312His3-(32-43)-peptide
PRO_0000021436
Peptide33 – 4412His3-(33-44)-peptide
PRO_0000021437
Peptide33 – 4311His3-(33-43)-peptide
PRO_0000021438
Peptide34 – 4411His3-(34-44)-peptide
PRO_0000021439
Peptide34 – 4310His3-(34-43)-peptide
PRO_0000021440
Peptide45 – 517His3-(45-51)-peptide
PRO_0000021441
Peptide47 – 515His3-(47-51)-peptide
PRO_0000021442
Peptide48 – 514His3-(48-51)-peptide
PRO_0000021443

Sites

Metal binding341Zinc
Site321Important for candidacidal activity
Site411Important for candidacidal activity
Site431Not sulfated
Site471Not sulfated
Site491Not sulfated

Natural variations

Natural variant411R → Q in histatin-3-2; loss of the proteolytic cleavage site. Ref.6
Corresponds to variant rs1136511 [ dbSNP | Ensembl ].
VAR_005288
Natural variant47 – 515Missing in histatin-3-2.
Corresponds to variant rs17147990 [ dbSNP | Ensembl ].
VAR_005289

Experimental info

Mutagenesis311R → I: No effect on candidacidal activity of His3-(20-43)-peptide. Ref.10
Mutagenesis321K → T or E: 3-fold reduction in candidacidal activity of His3-(20-43)-peptide. Ref.10
Mutagenesis361K → N: No effect on candidacidal activity of His3-(20-43)-peptide. Ref.10
Mutagenesis381H → P: No effect on candidacidal activity of His3-(20-43)-peptide. Ref.10
Mutagenesis401H → L or R: No effect on candidacidal activity of His3-(20-43)-peptide. Ref.10
Mutagenesis411R → G: 10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32. Ref.10

Sequences

Sequence LengthMass (Da)Tools
P15516 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: AFCCB4B32083FD65

FASTA516,149
        10         20         30         40         50 
MKFFVFALIL ALMLSMTGAD SHAKRHHGYK RKFHEKHHSH RGYRSNYLYD N 

« Hide

References

« Hide 'large scale' references
[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]"Molecular cloning of human submandibular histatins."
Vanderspek J.C., Offner G.D., Troxler R.F., Oppenheim F.G.
Arch. Oral Biol. 35:137-143(1990) [PubMed] [Europe PMC] [Abstract]
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]"Salivary peptidomics."
Amado F., Lobo M.J., Domingues P., Duarte J.A., Vitorino R.
Expert Rev. Proteomics 7:709-721(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PEPTIDE NOMENCLATURE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRB32541.
RefSeqNP_000191.1. NM_000200.2.
UniGeneHs.654442.

3D structure databases

ProteinModelPortalP15516.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP15516. 2 interactions.
MINTMINT-8415913.
STRING9606.ENSP00000370445.

Protein family/group databases

TCDB1.C.79.1.1. the channel-forming histatin antimicrobial peptide (histatin) family.

Proteomic databases

PaxDbP15516.
PRIDEP15516.

Protocols and materials databases

DNASU3347.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000526767; ENSP00000437158; ENSG00000205649.
ENST00000530128; ENSP00000432561; ENSG00000205649.
GeneID3347.
KEGGhsa:3347.
UCSCuc003hew.2. human.

Organism-specific databases

CTD3347.
GeneCardsGC04P070894.
HGNCHGNC:5284. HTN3.
MIM142702. gene.
neXtProtNX_P15516.
PharmGKBPA29547.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG273986.
HOGENOMHOG000112905.
HOVERGENHBG005970.
InParanoidP15516.
KOK13913.
OMAMLSMTGA.
OrthoDBEOG7TTQBV.
PhylomeDBP15516.
TreeFamTF341637.

Gene expression databases

BgeeP15516.
CleanExHS_HTN3.
GenevestigatorP15516.

Family and domain databases

ProtoNetSearch...

Other

ChiTaRSHTN3. human.
GeneWikiHTN3.
GenomeRNAi3347.
NextBio13240.
PROP15516.
SOURCESearch...

Entry information

Entry nameHIS3_HUMAN
AccessionPrimary (citable) accession number: P15516
Secondary accession number(s): Q16243, Q502Z1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM