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P15516

- HIS3_HUMAN

UniProt

P15516 - HIS3_HUMAN

Protein

Histatin-3

Gene

HTN3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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
    2. protein binding Source: IntAct

    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

    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

    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.
    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.
    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

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    MKFFVFALIL ALMLSMTGAD SHAKRHHGYK RKFHEKHHSH RGYRSNYLYD   50
    N 51
    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.
    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.
    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 .
    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.
    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.
    Genevestigatori P15516.

    Family and domain databases

    ProtoNeti Search...

    Publicationsi

    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 1, 2014
    This is version 131 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