ID   HIS3_HUMAN              Reviewed;          51 AA.
AC   P15516; Q16243; Q502Z1;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 2.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Histatin-3;
DE   AltName: Full=Basic histidine-rich protein;
DE            Short=Hst;
DE   AltName: Full=Histatin 3 {ECO:0000303|PubMed:20973643};
DE            Short=Hst 3 {ECO:0000303|PubMed:18650243};
DE   AltName: Full=Histidine-rich protein 3;
DE   AltName: Full=PB;
DE   Contains:
DE     RecName: Full=Histatin-3;
DE   Contains:
DE     RecName: Full=His3-(20-44)-peptide;
DE              Short=His3 20/44;
DE     AltName: Full=His3-(1-25)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 1/25 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 6 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-3 1/25;
DE     AltName: Full=Histatin-6;
DE   Contains:
DE     RecName: Full=His3-(20-43)-peptide;
DE              Short=His3 20/43;
DE     AltName: Full=His3-(1-24)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 1/24 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 5 {ECO:0000303|PubMed:20973643};
DE              Short=Hst 5 {ECO:0000303|PubMed:18650243};
DE     AltName: Full=Histatin-3 1/24;
DE     AltName: Full=Histatin-5 {ECO:0000303|PubMed:8945538};
DE   Contains:
DE     RecName: Full=His3-(20-32)-peptide;
DE              Short=His3 20/32;
DE     AltName: Full=His3-(1-13)-peptide;
DE              Short=His3 1/13;
DE     AltName: Full=Histatin-3 1/13;
DE   Contains:
DE     RecName: Full=His3-(20-31)-peptide;
DE              Short=His3 20/31;
DE     AltName: Full=His3-(1-12)-peptide;
DE              Short=His3 1/12;
DE     AltName: Full=Histatin-3 1/12;
DE   Contains:
DE     RecName: Full=His3-(20-30)-peptide;
DE              Short=His3 20/30;
DE     AltName: Full=His3-(1-11)-peptide;
DE              Short=His3 1/11;
DE     AltName: Full=Histatin-3 1/11;
DE   Contains:
DE     RecName: Full=His3-(24-32)-peptide;
DE              Short=His3 24/32;
DE     AltName: Full=His3-(5-13)-peptide;
DE              Short=His3 5/13;
DE     AltName: Full=Histatin-3 5/13;
DE   Contains:
DE     RecName: Full=His3-(24-31)-peptide;
DE              Short=His3 24/31;
DE     AltName: Full=His3-(5-12)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 5/12 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 11 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-11;
DE     AltName: Full=Histatin-3 5/12;
DE   Contains:
DE     RecName: Full=His3-(24-30)-peptide;
DE              Short=His3 24/30;
DE     AltName: Full=His3-(5-11)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 5/11 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 12 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-12;
DE     AltName: Full=Histatin-3 5/11;
DE   Contains:
DE     RecName: Full=His3-(25-32)-peptide;
DE              Short=His3 25/32;
DE     AltName: Full=His3-(6-13)-peptide;
DE              Short=His3 6/13;
DE     AltName: Full=Histatin-3 6/13;
DE   Contains:
DE     RecName: Full=His3-(25-30)-peptide;
DE              Short=His3 25/30;
DE     AltName: Full=His3-(6-11)-peptide;
DE              Short=His3 6/11;
DE     AltName: Full=Histatin-3 6/11;
DE   Contains:
DE     RecName: Full=His3-(26-32)-peptide;
DE              Short=His3 26/32;
DE     AltName: Full=His3-(7-13)-peptide;
DE              Short=His3 7/13;
DE     AltName: Full=Histatin-3 7/13;
DE   Contains:
DE     RecName: Full=His3-(26-31)-peptide;
DE              Short=His3 26/31;
DE     AltName: Full=His3-(7-12)-peptide;
DE              Short=His3 7/12;
DE     AltName: Full=Histatin-3 7/12;
DE   Contains:
DE     RecName: Full=His3-(26-30)-peptide;
DE              Short=His3 26/30;
DE     AltName: Full=His3-(7-11)-peptide;
DE              Short=His3 7/11;
DE     AltName: Full=Histatin-3 7/11;
DE   Contains:
DE     RecName: Full=His3-(31-51)-peptide;
DE              Short=His3 31/51;
DE     AltName: Full=His3-(12-32)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 12/32 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 4 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-3 12/32;
DE     AltName: Full=Histatin-4;
DE   Contains:
DE     RecName: Full=His3-(31-44)-peptide;
DE              Short=His3 31/44;
DE     AltName: Full=His3-(12-25)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 12/25 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 9 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-3 12/25;
DE     AltName: Full=Histatin-9;
DE   Contains:
DE     RecName: Full=His3-(31-43)-peptide;
DE              Short=His3 31/43;
DE     AltName: Full=His3-(12-24)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 12/24 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 7 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-3 12/24;
DE     AltName: Full=Histatin-7;
DE   Contains:
DE     RecName: Full=His3-(32-44)-peptide;
DE              Short=His3 32/44;
DE     AltName: Full=His3-(13-25)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 13/25 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 10 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-10;
DE     AltName: Full=Histatin-3 13/25;
DE   Contains:
DE     RecName: Full=His3-(32-43)-peptide;
DE              Short=His3 32-43;
DE     AltName: Full=His3-(13-24)-peptide {ECO:0000303|PubMed:20973643};
DE              Short=His3 13/24 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin 8 {ECO:0000303|PubMed:20973643};
DE     AltName: Full=Histatin-3 13/24;
DE     AltName: Full=Histatin-8;
DE   Contains:
DE     RecName: Full=His3-(33-44)-peptide;
DE              Short=His3 33/44;
DE     AltName: Full=His3-(14-25)-peptide;
DE              Short=His3 14/25;
DE     AltName: Full=Histatin-3 14/25;
DE   Contains:
DE     RecName: Full=His3-(33-43)-peptide;
DE              Short=His3 33/43;
DE     AltName: Full=His3-(14-24)-peptide;
DE              Short=His3 14/24;
DE     AltName: Full=Histatin-3 14/24;
DE   Contains:
DE     RecName: Full=His3-(34-44)-peptide;
DE              Short=His3 34/44;
DE     AltName: Full=His3-(15-25)-peptide;
DE              Short=His3 15/25;
DE     AltName: Full=Histatin-3 15/25;
DE   Contains:
DE     RecName: Full=His3-(34-43)-peptide;
DE              Short=His3 34/43;
DE     AltName: Full=His3-(15-24)-peptide;
DE              Short=His3 15/24;
DE     AltName: Full=Histatin-3 15/24;
DE   Contains:
DE     RecName: Full=His3-(45-51)-peptide;
DE              Short=His3 45/51;
DE     AltName: Full=His3-(26-32)-peptide;
DE              Short=His3 26/32;
DE     AltName: Full=Histatin-3 26/32;
DE   Contains:
DE     RecName: Full=His3-(47-51)-peptide;
DE              Short=His3 47/51;
DE     AltName: Full=His3-(28-32)-peptide;
DE              Short=His3 28/32;
DE     AltName: Full=Histatin-3 28/32;
DE   Contains:
DE     RecName: Full=His3-(48-51)-peptide;
DE              Short=His3 48/51;
DE     AltName: Full=His3-(29-32)-peptide;
DE              Short=His3 29/32;
DE     AltName: Full=Histatin-3 29/32;
DE   Flags: Precursor;
GN   Name=HTN3 {ECO:0000312|HGNC:HGNC:5284}; Synonyms=HIS2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2719677; DOI=10.1016/0006-291x(89)92460-1;
RA   Sabatini L.M., Azen E.A.;
RT   "Histatins, a family of salivary histidine-rich proteins, are encoded by at
RT   least two loci (HIS1 and HIS2).";
RL   Biochem. Biophys. Res. Commun. 160:495-502(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3426601; DOI=10.1016/0006-291x(87)90436-0;
RA   Dickinson D.P., Ridall A.L., Levine M.J.;
RT   "Human submandibular gland statherin and basic histidine-rich peptide are
RT   encoded by highly abundant mRNA's derived from a common ancestral
RT   sequence.";
RL   Biochem. Biophys. Res. Commun. 149:784-790(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2344289; DOI=10.1016/0003-9969(90)90175-a;
RA   Vanderspek J.C., Offner G.D., Troxler R.F., Oppenheim F.G.;
RT   "Molecular cloning of human submandibular histatins.";
RL   Arch. Oral Biol. 35:137-143(1990).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8336540; DOI=10.1093/oxfordjournals.molbev.a040022;
RA   Chen Z.W.;
RT   "Nucleotide sequence analysis of the human salivary protein genes HIS1 and
RT   HIS2, and evolution of the STATH/HIS gene family.";
RL   Mol. Biol. Evol. 10:497-511(1993).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skeletal muscle, and Thyroid;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-51, VARIANTS HISTATIN-3-2 GLN-41
RP   AND 47-TYR--ASN-51 DEL, AND POLYMORPHISM.
RC   TISSUE=Saliva;
RX   PubMed=7951254; DOI=10.1002/humu.1380040103;
RA   Sabatini L.M., Azen E.A.;
RT   "Two coding change mutations in the HIS2(2) allele characterize the
RT   salivary histatin 3-2 protein variant.";
RL   Hum. Mutat. 4:12-19(1994).
RN   [7]
RP   PROTEIN SEQUENCE OF 20-51, AND FUNCTION.
RC   TISSUE=Parotid gland;
RX   PubMed=3286634; DOI=10.1016/s0021-9258(18)68522-9;
RA   Oppenheim F.G., Xu T., McMillian F.M., Levitz S.M., Diamond R.D.,
RA   Offner G.D., Troxler R.F.;
RT   "Histatins, a novel family of histidine-rich proteins in human parotid
RT   secretion. Isolation, characterization, primary structure, and fungistatic
RT   effects on Candida albicans.";
RL   J. Biol. Chem. 263:7472-7477(1988).
RN   [8]
RP   PROTEIN SEQUENCE OF 20-42.
RC   TISSUE=Saliva;
RX   PubMed=2372245; DOI=10.1016/0003-9969(90)90202-l;
RA   Sugiyama K., Ogino T., Ogata K.;
RT   "Rapid purification and characterization of histatins (histidine-rich
RT   polypeptides) from human whole saliva.";
RL   Arch. Oral Biol. 35:415-419(1990).
RN   [9]
RP   PROTEIN SEQUENCE OF 20-32, AND IDENTIFICATION BY MASS SPECTROMETRY OF 24
RP   PEPTIDE FRAGMENTS.
RC   TISSUE=Saliva;
RX   PubMed=15272024; DOI=10.1074/jbc.m404322200;
RA   Castagnola M., Inzitari R., Rossetti D.V., Olmi C., Cabras T., Piras V.,
RA   Nicolussi P., Sanna M.T., Pellegrini M., Giardina B., Messana I.;
RT   "A cascade of 24 histatins (histatin 3 fragments) in human saliva.
RT   Suggestions for a pre-secretory sequential cleavage pathway.";
RL   J. Biol. Chem. 279:41436-41443(2004).
RN   [10]
RP   FUNCTION, AND MUTAGENESIS OF ARG-31; LYS-32; LYS-36; HIS-38; HIS-40 AND
RP   ARG-41.
RX   PubMed=8945538; DOI=10.1128/iai.64.12.5000-5007.1996;
RA   Tsai H., Raj P.A., Bobek L.A.;
RT   "Candidacidal activity of recombinant human salivary histatin-5 and
RT   variants.";
RL   Infect. Immun. 64:5000-5007(1996).
RN   [11]
RP   DOMAIN.
RX   PubMed=10423240; DOI=10.1021/bi990212c;
RA   Melino S., Rufini S., Sette M., Morero R., Grottesi A., Paci M.,
RA   Petruzzelli R.;
RT   "Zn(2+) ions selectively induce antimicrobial salivary peptide histatin-5
RT   to fuse negatively charged vesicles. Identification and characterization of
RT   a zinc-binding motif present in the functional domain.";
RL   Biochemistry 38:9626-9633(1999).
RN   [12]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=10066791; DOI=10.1074/jbc.274.11.7286;
RA   Helmerhorst E.J., Breeuwer P., van't Hof W., Walgreen-Weterings E.,
RA   Oomen L.C., Veerman E.C., Amerongen A.V., Abee T.;
RT   "The cellular target of histatin 5 on Candida albicans is the energized
RT   mitochondrion.";
RL   J. Biol. Chem. 274:7286-7291(1999).
RN   [13]
RP   FUNCTION.
RX   PubMed=11083804; DOI=10.1128/iai.68.12.6848-6856.2000;
RA   Koshlukova S.E., Araujo M.W., Baev D., Edgerton M.;
RT   "Released ATP is an extracellular cytotoxic mediator in salivary histatin
RT   5-induced killing of Candida albicans.";
RL   Infect. Immun. 68:6848-6856(2000).
RN   [14]
RP   ZINC-BINDING SITE; HISTATIN 5, AND DOMAIN.
RX   PubMed=11226423; DOI=10.1016/s0014-5793(01)02157-3;
RA   Grogan J., McKnight C.J., Troxler R.F., Oppenheim F.G.;
RT   "Zinc and copper bind to unique sites of histatin 5.";
RL   FEBS Lett. 491:76-80(2001).
RN   [15]
RP   FUNCTION; HISTATIN 5.
RX   PubMed=11179305; DOI=10.1128/iai.69.3.1402-1408.2001;
RA   Gusman H., Travis J., Helmerhorst E.J., Potempa J., Troxler R.F.,
RA   Oppenheim F.G.;
RT   "Salivary histatin 5 is an inhibitor of both host and bacterial enzymes
RT   implicated in periodontal disease.";
RL   Infect. Immun. 69:1402-1408(2001).
RN   [16]
RP   FUNCTION.
RX   PubMed=11717389; DOI=10.1073/pnas.141366998;
RA   Helmerhorst E.J., Troxler R.F., Oppenheim F.G.;
RT   "The human salivary peptide histatin 5 exerts its antifungal activity
RT   through the formation of reactive oxygen species.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:14637-14642(2001).
RN   [17]
RP   INTERACTION WITH SSA1 AND SSA2; HISTATIN 3 AND HISTATIN 5, AND FUNCTION.
RX   PubMed=12761219; DOI=10.1074/jbc.m300680200;
RA   Li X.S., Reddy M.S., Baev D., Edgerton M.;
RT   "Candida albicans Ssa1/2p is the cell envelope binding protein for human
RT   salivary histatin 5.";
RL   J. Biol. Chem. 278:28553-28561(2003).
RN   [18]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=12939362; DOI=10.1177/154405910308200917;
RA   Dong J., Vylkova S., Li X.S., Edgerton M.;
RT   "Calcium blocks fungicidal activity of human salivary histatin 5 through
RT   disruption of binding with Candida albicans.";
RL   J. Dent. Res. 82:748-752(2003).
RN   [19]
RP   FUNCTION.
RX   PubMed=15485849; DOI=10.1074/jbc.m411031200;
RA   Baev D., Rivetta A., Vylkova S., Sun J.N., Zeng G.F., Slayman C.L.,
RA   Edgerton M.;
RT   "The TRK1 potassium transporter is the critical effector for killing of
RT   Candida albicans by the cationic protein, Histatin 5.";
RL   J. Biol. Chem. 279:55060-55072(2004).
RN   [20]
RP   SUBCELLULAR LOCATION.
RX   PubMed=14966203; DOI=10.1177/002215540405200307;
RA   Ahmad M., Piludu M., Oppenheim F.G., Helmerhorst E.J., Hand A.R.;
RT   "Immunocytochemical localization of histatins in human salivary glands.";
RL   J. Histochem. Cytochem. 52:361-370(2004).
RN   [21]
RP   LACK OF SULFATION AT TYR-43; TYR-47 AND TYR-49, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=17503797; DOI=10.1021/pr0700706;
RA   Cabras T., Fanali C., Monteiro J.A., Amado F., Inzitari R., Desiderio C.,
RA   Scarano E., Giardina B., Castagnola M., Messana I.;
RT   "Tyrosine polysulfation of human salivary histatin 1. A post-translational
RT   modification specific of the submandibular gland.";
RL   J. Proteome Res. 6:2472-2480(2007).
RN   [22]
RP   FUNCTION.
RX   PubMed=18650243; DOI=10.1096/fj.08-112003;
RA   Oudhoff M.J., Bolscher J.G., Nazmi K., Kalay H., van 't Hof W.,
RA   Amerongen A.V., Veerman E.C.;
RT   "Histatins are the major wound-closure stimulating factors in human saliva
RT   as identified in a cell culture assay.";
RL   FASEB J. 22:3805-3812(2008).
RN   [23]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=18974864; DOI=10.1371/journal.ppat.1000190;
RA   Mochon A.B., Liu H.;
RT   "The antimicrobial peptide histatin-5 causes a spatially restricted
RT   disruption on the Candida albicans surface, allowing rapid entry of the
RT   peptide into the cytoplasm.";
RL   PLoS Pathog. 4:e1000190-e1000190(2008).
RN   [24]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=19846304; DOI=10.1016/j.bmcl.2009.09.119;
RA   Tay W.M., Hanafy A.I., Angerhofer A., Ming L.J.;
RT   "A plausible role of salivary copper in antimicrobial activity of histatin-
RT   5--metal binding and oxidative activity of its copper complex.";
RL   Bioorg. Med. Chem. Lett. 19:6709-6712(2009).
RN   [25]
RP   PEPTIDE NOMENCLATURE.
RX   PubMed=20973643; DOI=10.1586/epr.10.48;
RA   Amado F., Lobo M.J., Domingues P., Duarte J.A., Vitorino R.;
RT   "Salivary peptidomics.";
RL   Expert Rev. Proteomics 7:709-721(2010).
RN   [26]
RP   FUNCTION, AND CAUTION.
RX   PubMed=20487276; DOI=10.1111/j.1365-2958.2010.07210.x;
RA   Jang W.S., Bajwa J.S., Sun J.N., Edgerton M.;
RT   "Salivary histatin 5 internalization by translocation, but not endocytosis,
RT   is required for fungicidal activity in Candida albicans.";
RL   Mol. Microbiol. 77:354-370(2010).
RN   [27]
RP   FUNCTION.
RX   PubMed=22033918; DOI=10.1074/jbc.m111.311175;
RA   Kumar R., Chadha S., Saraswat D., Bajwa J.S., Li R.A., Conti H.R.,
RA   Edgerton M.;
RT   "Histatin 5 uptake by Candida albicans utilizes polyamine transporters Dur3
RT   and Dur31 proteins.";
RL   J. Biol. Chem. 286:43748-43758(2011).
RN   [28]
RP   FUNCTION.
RX   PubMed=23613860; DOI=10.1371/journal.pone.0061480;
RA   Tati S., Jang W.S., Li R., Kumar R., Puri S., Edgerton M.;
RT   "Histatin 5 resistance of Candida glabrata can be reversed by insertion of
RT   Candida albicans polyamine transporter-encoding genes DUR3 and DUR31.";
RL   PLoS ONE 8:e61480-e61480(2013).
RN   [29]
RP   FUNCTION.
RX   PubMed=26379655; DOI=10.3389/fmicb.2015.00885;
RA   Moffa E.B., Mussi M.C., Xiao Y., Garrido S.S., Machado M.A.,
RA   Giampaolo E.T., Siqueira W.L.;
RT   "Histatin 5 inhibits adhesion of C. albicans to Reconstructed Human Oral
RT   Epithelium.";
RL   Front. Microbiol. 6:885-885(2015).
RN   [30]
RP   MISCELLANEOUS.
RX   PubMed=27390786; DOI=10.18388/abp.2016_1318;
RA   Bochenska O., Rapala-Kozik M., Wolak N., Aoki W., Ueda M., Kozik A.;
RT   "The action of ten secreted aspartic proteases of pathogenic yeast Candida
RT   albicans on major human salivary antimicrobial peptide, histatin 5.";
RL   Acta Biochim. Pol. 63:403-410(2016).
RN   [31]
RP   FUNCTION, AND INTERACTION WITH HSPA8.
RX   PubMed=26775844; DOI=10.1016/j.bbrc.2016.01.072;
RA   Imamura Y., Wang P.L., Masuno K., Sogawa N.;
RT   "Salivary protein histatin 3 regulates cell proliferation by enhancing
RT   p27(Kip1) and heat shock cognate protein 70 ubiquitination.";
RL   Biochem. Biophys. Res. Commun. 470:269-274(2016).
RN   [32]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=28261570; DOI=10.3389/fcimb.2017.00041;
RA   Du H., Puri S., McCall A., Norris H.L., Russo T., Edgerton M.;
RT   "Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against
RT   ESKAPE Pathogens.";
RL   Front. Cell. Infect. Microbiol. 7:41-41(2017).
RN   [33]
RP   FUNCTION, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS OF HIS-22;
RP   26-HIS-HIS-27 AND 37-HIS-HIS-38.
RX   PubMed=28763199; DOI=10.1021/acs.biochem.7b00348;
RA   Conklin S.E., Bridgman E.C., Su Q., Riggs-Gelasco P., Haas K.L.,
RA   Franz K.J.;
RT   "Specific Histidine Residues Confer Histatin Peptides with Copper-Dependent
RT   Activity against Candida albicans.";
RL   Biochemistry 56:4244-4255(2017).
RN   [34]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=32225006; DOI=10.3390/cells9040795;
RA   Ma D., Sun W., Nazmi K., Veerman E.C.I., Bikker F.J., Jaspers R.T.,
RA   Bolscher J.G.M., Wu G.;
RT   "Salivary Histatin 1 and 2 Are Targeted to Mitochondria and Endoplasmic
RT   Reticulum in Human Cells.";
RL   Cells 9:0-0(2020).
RN   [35]
RP   FUNCTION, SUBUNIT, ACTIVITY REGULATION, AND DOMAIN.
RX   PubMed=32751915; DOI=10.3390/jof6030124;
RA   Norris H.L., Kumar R., Ong C.Y., Xu D., Edgerton M.;
RT   "Zinc Binding by Histatin 5 Promotes Fungicidal Membrane Disruption in C.
RT   albicans and C. glabrata.";
RL   J. Fungi 6:0-0(2020).
RN   [36]
RP   MISCELLANEOUS, AND MUTAGENESIS OF LYS-30; LYS-32; GLU-35 AND LYS-36.
RX   PubMed=31675138; DOI=10.1002/pro.3767;
RA   Ikonomova S.P., Moghaddam-Taaheri P., Wang Y., Doolin M.T., Stroka K.M.,
RA   Hube B., Karlsson A.J.;
RT   "Effects of histatin 5 modifications on antifungal activity and kinetics of
RT   proteolysis.";
RL   Protein Sci. 29:480-493(2020).
CC   -!- FUNCTION: Histatins are cationic and histidine-rich peptides mainly
CC       found in the saliva of higher primates (PubMed:3286634). They are
CC       considered to be major precursors of the protective proteinaceous
CC       structure on tooth surfaces (enamel pellicle). Hsts can be divided into
CC       two major groups according to their biological functions: antimicrobial
CC       Hsts (e.g. Hst 5/HTN3) and cell-activating Hsts (e.g. Hst 1/HTN1, Hst
CC       2/HTN1 and Hst 3/HTN3) (PubMed:32225006). {ECO:0000269|PubMed:32225006,
CC       ECO:0000269|PubMed:3286634}.
CC   -!- FUNCTION: [Histatin-3]: Histatin 3 (Hst 3) is mostly involved in cell
CC       migration and wound healing in the oral cavity (PubMed:18650243). Also
CC       stimulates cell proliferation after binding to heat shock protein
CC       HSC70, which enhances HSC70-CDKN1B complex formation and subsequent
CC       ubiquitination during G1/S transition (PubMed:26775844). Also displays
CC       antifungal activity against pathogenic yeast Candida albicans, however
CC       with less effectiveness than Hst 5 (PubMed:3286634, PubMed:11083804).
CC       {ECO:0000269|PubMed:11083804, ECO:0000269|PubMed:18650243,
CC       ECO:0000269|PubMed:26775844, ECO:0000269|PubMed:3286634}.
CC   -!- FUNCTION: [His3-(20-43)-peptide]: Histatin 5 (Hst 5), a fragment of Hst
CC       3, is the major histatin exhibiting antifungal and antibacterial
CC       activities (PubMed:2372245, PubMed:8945538, PubMed:10066791,
CC       PubMed:11083804, PubMed:11179305, PubMed:11717389, PubMed:12939362,
CC       PubMed:15485849). It is effective against pathogenic yeast C. albicans,
CC       C. neoformans, C. glabrata and S. cerevisiae as well as ESKAPE
CC       bacterial pathogens (PubMed:2372245, PubMed:8945538, PubMed:18974864,
CC       PubMed:23613860, PubMed:28261570). Secreted Hst 5 mediates a multi-step
CC       intracellular mechanism of action against the pathogen. Depending on
CC       peptide concentration and pathogen, uptake across the membrane can
CC       occur through transporters, direct interaction with plasma membrane
CC       and/or receptor-mediated endocytosis (PubMed:18974864, PubMed:20487276,
CC       PubMed:28261570). Binds C. albicans cell wall proteins SSA1 and SSA2
CC       and glycans in an energy-independent manner, then is taken up by the
CC       cells through fungal polyamine transporters DUR3 and DUR31 in an
CC       energy-dependent manner (PubMed:12761219, PubMed:20487276,
CC       PubMed:22033918, PubMed:23613860). Internalized Hst5 is then targeted
CC       to the energized mitochondrion to induce reactive oxygen species (ROS)
CC       formation and subsequent release of intracellular non-lytic ATP which
CC       ultimately leads to fungal cell death (PubMed:10066791,
CC       PubMed:11717389, PubMed:11083804). In addition, inhibits C. albicans
CC       TRK1 potassium-transporter which causes exudation of intracellular
CC       K(+), generating an osmotic imbalance leading to delayed membrane lysis
CC       and cell death (PubMed:15485849). Also acts as a potent inhibitor of
CC       bacterial proteases such as Lys-gingipain and Arg-gingipain (rgpB) from
CC       P. gingivalis as well as human metalloproteases MMP2 and MMP9
CC       (PubMed:11179305). The binding of metals such as zinc, copper or nickel
CC       with Hst 5 results in the protection of the enamel and antimicrobial
CC       activities such as the inhibition of microbial growth by decreasing the
CC       metal concentration, the formation of ROS commonly associated with
CC       redox-active metals, the induction of membrane disruption mediated by
CC       zinc binding (PubMed:19846304, PubMed:28261570, PubMed:28763199,
CC       PubMed:32751915). Also involved in coating oral surfaces in the form of
CC       a salivary film which reduces colonization by C. albicans on epithelial
CC       cell surfaces (PubMed:26379655). Secreted Hst 5 can also internalize
CC       mammalian epithelial cells and target the mitochondria although it does
CC       not exert cytotoxic effects in these cells (PubMed:32225006). In
CC       contrast with Hst 3, not able to promote wound healing in mammalian
CC       host cells (PubMed:18650243). {ECO:0000269|PubMed:10066791,
CC       ECO:0000269|PubMed:11083804, ECO:0000269|PubMed:11179305,
CC       ECO:0000269|PubMed:11717389, ECO:0000269|PubMed:12761219,
CC       ECO:0000269|PubMed:12939362, ECO:0000269|PubMed:15485849,
CC       ECO:0000269|PubMed:18650243, ECO:0000269|PubMed:18974864,
CC       ECO:0000269|PubMed:19846304, ECO:0000269|PubMed:20487276,
CC       ECO:0000269|PubMed:22033918, ECO:0000269|PubMed:23613860,
CC       ECO:0000269|PubMed:2372245, ECO:0000269|PubMed:26379655,
CC       ECO:0000269|PubMed:28261570, ECO:0000269|PubMed:28763199,
CC       ECO:0000269|PubMed:32225006, ECO:0000269|PubMed:32751915,
CC       ECO:0000269|PubMed:8945538}.
CC   -!- ACTIVITY REGULATION: [His3-(20-43)-peptide]: Metal binding such as zinc
CC       and copper increases antimicrobial activity (PubMed:32751915,
CC       PubMed:19846304, PubMed:28763199). Conjugation with spermidine
CC       increases bactericidal efficiency against ESKAPE pathogens
CC       (PubMed:28261570). Calcium inhibits antifungal activity against C.
CC       albicans at physiological concentrations by disrupting Hst 5 binding
CC       with C. albicans (PubMed:12939362). Antifungal activity is also reduced
CC       by some salivary ions as Mg(2+), Cl(-) and CO(3-) (PubMed:12939362).
CC       Fe(3+) also decreases antifungal activity (PubMed:28763199). Antifungal
CC       activity is also decreased at pH above 8 and below 4 (PubMed:12939362).
CC       {ECO:0000269|PubMed:12939362, ECO:0000269|PubMed:19846304,
CC       ECO:0000269|PubMed:28261570, ECO:0000269|PubMed:28763199,
CC       ECO:0000269|PubMed:32751915}.
CC   -!- SUBUNIT: [Histatin-3]: Homodimer (PubMed:12761219). Interacts with
CC       HSPA8; the interaction increases binding affinity of HSPA8 to CDKN1B
CC       (PubMed:26775844). {ECO:0000269|PubMed:12761219,
CC       ECO:0000269|PubMed:26775844}.
CC   -!- SUBUNIT: [His3-(20-43)-peptide]: Homodimer (PubMed:12761219,
CC       PubMed:32751915). Interacts with Candida albicans SSA1 and SSA2
CC       proteins (PubMed:12761219). {ECO:0000269|PubMed:12761219,
CC       ECO:0000269|PubMed:32751915}.
CC   -!- INTERACTION:
CC       P15516; Q9UBS4: DNAJB11; NbExp=3; IntAct=EBI-738783, EBI-713113;
CC       P15516; P95493: rgpB; Xeno; NbExp=7; IntAct=EBI-738783, EBI-8505881;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14966203}.
CC       Note=Secreted by serous acinar and demilune cells.
CC       {ECO:0000269|PubMed:14966203}.
CC   -!- SUBCELLULAR LOCATION: [His3-(20-43)-peptide]: Secreted
CC       {ECO:0000269|PubMed:14966203}. Mitochondrion
CC       {ECO:0000269|PubMed:32225006}. Note=Targeted to mitochondria in
CC       pathogen cells after internalization (PubMed:10066791). Also localized
CC       in the vacuole in pathogen cells (PubMed:18974864). Also co-localized
CC       with mitochondria after internalization in host mammalian cells
CC       (PubMed:32225006). {ECO:0000269|PubMed:10066791,
CC       ECO:0000269|PubMed:18974864, ECO:0000269|PubMed:32225006}.
CC   -!- DOMAIN: [His3-(20-43)-peptide]: The ATCUN motif mediates Cu(2+) binding
CC       and the Bis-His motif mediates Cu(1+) binding and are necessary for
CC       antifungal activity (PubMed:11226423, PubMed:28763199). The HExxH motif
CC       mediates binding to Zin(2+) which is important for the stabilization of
CC       a helical conformation in an hydrophobic environment, Hst5 dimerization
CC       and antifungal activity (PubMed:10423240, PubMed:11226423,
CC       PubMed:32751915). {ECO:0000269|PubMed:10423240,
CC       ECO:0000269|PubMed:11226423, ECO:0000269|PubMed:28763199,
CC       ECO:0000269|PubMed:32751915}.
CC   -!- PTM: 24 proteolytic products are found in saliva.
CC       {ECO:0000269|PubMed:15272024}.
CC   -!- POLYMORPHISM: There are two alleles of HTN3, HIS2(1) (shown here) and
CC       HIS2(2) that codes for the variant histatin-3-2 found primarily and in
CC       high frequencies in black populations. {ECO:0000269|PubMed:7951254}.
CC   -!- MISCELLANEOUS: The recommended nomenclature of salivary peptides
CC       follows published guidelines (PubMed:20973643). In agreement with the
CC       authors, it has been decided to indicate the boundaries of the peptides
CC       according to the positions within the precursor, and not in the mature
CC       protein, as has formerly been proposed. {ECO:0000305|PubMed:20973643}.
CC   -!- MISCELLANEOUS: [His3-(20-43)-peptide]: Proteolytically cleaved by C.
CC       albicans SAP proteases with the decreased cleavage rate order of
CC       SAP2>SAP9>SAP3>SAP7>SAP4>SAP1>SAP8, leading to Hst 5 degradation and
CC       antifungal activity inactivation (PubMed:31675138, PubMed:27390786).
CC       Histatin 1, histatin 3 and histatin 5 constitute more than 80% of the
CC       total histatin concentration (Probable). {ECO:0000269|PubMed:27390786,
CC       ECO:0000269|PubMed:31675138, ECO:0000305|PubMed:3286634}.
CC   -!- SIMILARITY: Belongs to the histatin/statherin family. {ECO:0000305}.
CC   -!- CAUTION: Hst 5 uptake into the pathogen cell by direct transfer across
CC       the membrane causing cell death has been questioned (PubMed:20487276).
CC       Moreover, endocytic vacuolar uptake was showed to be insignificant in
CC       terms of Hst 5 toxicity (PubMed:20487276).
CC       {ECO:0000269|PubMed:20487276}.
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DR   EMBL; M26665; AAA58646.1; -; mRNA.
DR   EMBL; M18372; AAA51830.1; -; mRNA.
DR   EMBL; L05514; AAA02746.1; -; Genomic_DNA.
DR   EMBL; L05513; AAA02746.1; JOINED; Genomic_DNA.
DR   EMBL; BC009791; AAH09791.1; -; mRNA.
DR   EMBL; BC095438; AAH95438.1; -; mRNA.
DR   EMBL; S74382; AAB32411.1; -; Genomic_DNA.
DR   CCDS; CCDS33999.1; -.
DR   PIR; B32541; B32541.
DR   RefSeq; NP_000191.1; NM_000200.2.
DR   AlphaFoldDB; P15516; -.
DR   SASBDB; P15516; -.
DR   BioGRID; 109579; 32.
DR   IntAct; P15516; 4.
DR   MINT; P15516; -.
DR   STRING; 9606.ENSP00000432561; -.
DR   TCDB; 1.C.79.1.1; the channel-forming histatin antimicrobial peptide (histatin) family.
DR   BioMuta; HTN3; -.
DR   MassIVE; P15516; -.
DR   PaxDb; 9606-ENSP00000432561; -.
DR   PeptideAtlas; P15516; -.
DR   ProteomicsDB; 53166; -.
DR   Antibodypedia; 24280; 20 antibodies from 10 providers.
DR   DNASU; 3347; -.
DR   Ensembl; ENST00000530128.5; ENSP00000432561.1; ENSG00000205649.9.
DR   Ensembl; ENST00000635585.1; ENSP00000489520.1; ENSG00000282967.4.
DR   Ensembl; ENST00000672568.1; ENSP00000500810.1; ENSG00000282967.4.
DR   Ensembl; ENST00000673563.1; ENSP00000500623.1; ENSG00000205649.9.
DR   Ensembl; ENST00000677679.1; ENSP00000504141.1; ENSG00000282967.4.
DR   GeneID; 3347; -.
DR   KEGG; hsa:3347; -.
DR   MANE-Select; ENST00000673563.1; ENSP00000500623.1; NM_000200.3; NP_000191.1.
DR   UCSC; uc003hew.2; human.
DR   AGR; HGNC:5284; -.
DR   CTD; 3347; -.
DR   DisGeNET; 3347; -.
DR   GeneCards; HTN3; -.
DR   HGNC; HGNC:5284; HTN3.
DR   HPA; ENSG00000205649; Tissue enriched (salivary).
DR   MIM; 142702; gene.
DR   neXtProt; NX_P15516; -.
DR   OpenTargets; ENSG00000205649; -.
DR   PharmGKB; PA29547; -.
DR   VEuPathDB; HostDB:ENSG00000205649; -.
DR   eggNOG; ENOG502TEIC; Eukaryota.
DR   GeneTree; ENSGT00940000164572; -.
DR   InParanoid; P15516; -.
DR   OMA; HEKHHSY; -.
DR   OrthoDB; 4682135at2759; -.
DR   PhylomeDB; P15516; -.
DR   TreeFam; TF341637; -.
DR   PathwayCommons; P15516; -.
DR   Reactome; R-HSA-6803157; Antimicrobial peptides.
DR   SignaLink; P15516; -.
DR   BioGRID-ORCS; 3347; 6 hits in 569 CRISPR screens.
DR   ChiTaRS; HTN3; human.
DR   GeneWiki; HTN3; -.
DR   GenomeRNAi; 3347; -.
DR   Pharos; P15516; Tbio.
DR   PRO; PR:P15516; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P15516; Protein.
DR   Bgee; ENSG00000205649; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 47 other cell types or tissues.
DR   ExpressionAtlas; P15516; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0060090; F:molecular adaptor activity; IMP:UniProtKB.
DR   GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR   GO; GO:0042742; P:defense response to bacterium; NAS:UniProtKB.
DR   GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR   GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:UniProtKB.
DR   GO; GO:0090303; P:positive regulation of wound healing; IDA:UniProtKB.
DR   DisProt; DP02206; -.
DR   InterPro; IPR030773; Histatin/statherin.
DR   PANTHER; PTHR15057:SF0; HISTATIN-3; 1.
DR   PANTHER; PTHR15057; STATHERIN; 1.
DR   Genevisible; P15516; HS.
PE   1: Evidence at protein level;
KW   Antibiotic; Antimicrobial; Biomineralization;
KW   Cleavage on pair of basic residues; Direct protein sequencing; Fungicide;
KW   Immunity; Innate immunity; Metal-binding; Mitochondrion;
KW   Reference proteome; Secreted; Signal; Zinc.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:15272024,
FT                   ECO:0000269|PubMed:2372245, ECO:0000269|PubMed:3286634"
FT   CHAIN           20..51
FT                   /note="Histatin-3"
FT                   /id="PRO_0000021418"
FT   PEPTIDE         20..44
FT                   /note="His3-(20-44)-peptide"
FT                   /id="PRO_0000021419"
FT   PEPTIDE         20..43
FT                   /note="His3-(20-43)-peptide"
FT                   /id="PRO_0000021420"
FT   PEPTIDE         20..32
FT                   /note="His3-(20-32)-peptide"
FT                   /id="PRO_0000021421"
FT   PEPTIDE         20..31
FT                   /note="His3-(20-31)-peptide"
FT                   /id="PRO_0000021422"
FT   PEPTIDE         20..30
FT                   /note="His3-(20-30)-peptide"
FT                   /id="PRO_0000021423"
FT   PEPTIDE         24..32
FT                   /note="His3-(24-32)-peptide"
FT                   /id="PRO_0000021424"
FT   PEPTIDE         24..31
FT                   /note="His3-(24-31)-peptide"
FT                   /id="PRO_0000021425"
FT   PEPTIDE         24..30
FT                   /note="His3-(24-30)-peptide"
FT                   /id="PRO_0000021426"
FT   PEPTIDE         25..32
FT                   /note="His3-(25-32)-peptide"
FT                   /id="PRO_0000021427"
FT   PEPTIDE         25..30
FT                   /note="His3-(25-30)-peptide"
FT                   /id="PRO_0000021428"
FT   PEPTIDE         26..32
FT                   /note="His3-(26-32)-peptide"
FT                   /id="PRO_0000021429"
FT   PEPTIDE         26..31
FT                   /note="His3-(26-31)-peptide"
FT                   /id="PRO_0000021430"
FT   PEPTIDE         26..30
FT                   /note="His3-(26-30)-peptide"
FT                   /id="PRO_0000021431"
FT   PEPTIDE         31..51
FT                   /note="His3-(31-51)-peptide"
FT                   /id="PRO_0000021432"
FT   PEPTIDE         31..44
FT                   /note="His3-(31-44)-peptide"
FT                   /id="PRO_0000021433"
FT   PEPTIDE         31..43
FT                   /note="His3-(31-43)-peptide"
FT                   /id="PRO_0000021434"
FT   PEPTIDE         32..44
FT                   /note="His3-(32-44)-peptide"
FT                   /id="PRO_0000021435"
FT   PEPTIDE         32..43
FT                   /note="His3-(32-43)-peptide"
FT                   /id="PRO_0000021436"
FT   PEPTIDE         33..44
FT                   /note="His3-(33-44)-peptide"
FT                   /id="PRO_0000021437"
FT   PEPTIDE         33..43
FT                   /note="His3-(33-43)-peptide"
FT                   /id="PRO_0000021438"
FT   PEPTIDE         34..44
FT                   /note="His3-(34-44)-peptide"
FT                   /id="PRO_0000021439"
FT   PEPTIDE         34..43
FT                   /note="His3-(34-43)-peptide"
FT                   /id="PRO_0000021440"
FT   PEPTIDE         45..51
FT                   /note="His3-(45-51)-peptide"
FT                   /id="PRO_0000021441"
FT   PEPTIDE         47..51
FT                   /note="His3-(47-51)-peptide"
FT                   /id="PRO_0000021442"
FT   PEPTIDE         48..51
FT                   /note="His3-(48-51)-peptide"
FT                   /id="PRO_0000021443"
FT   REGION          24..27
FT                   /note="Implicated in the interaction with HSPA8"
FT                   /evidence="ECO:0000269|PubMed:26775844"
FT   REGION          27..51
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           20..22
FT                   /note="ATCUN motif"
FT                   /evidence="ECO:0000269|PubMed:11226423,
FT                   ECO:0000269|PubMed:28763199"
FT   MOTIF           26..27
FT                   /note="Bis-His motif"
FT                   /evidence="ECO:0000269|PubMed:28763199"
FT   MOTIF           34..38
FT                   /note="HExxH motif"
FT                   /evidence="ECO:0000269|PubMed:10423240,
FT                   ECO:0000269|PubMed:11226423"
FT   COMPBIAS        27..41
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         34
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:11226423"
FT   SITE            32
FT                   /note="Important for candidacidal activity"
FT   SITE            41
FT                   /note="Important for candidacidal activity"
FT   SITE            43
FT                   /note="Not sulfated"
FT                   /evidence="ECO:0000269|PubMed:17503797"
FT   SITE            47
FT                   /note="Not sulfated"
FT                   /evidence="ECO:0000269|PubMed:17503797"
FT   SITE            49
FT                   /note="Not sulfated"
FT                   /evidence="ECO:0000269|PubMed:17503797"
FT   VARIANT         41
FT                   /note="R -> Q (in histatin-3-2; loss of the proteolytic
FT                   cleavage site; dbSNP:rs1136511)"
FT                   /evidence="ECO:0000269|PubMed:7951254"
FT                   /id="VAR_005288"
FT   VARIANT         47..51
FT                   /note="Missing (in histatin-3-2; dbSNP:rs17147990)"
FT                   /evidence="ECO:0000269|PubMed:7951254"
FT                   /id="VAR_005289"
FT   MUTAGEN         22
FT                   /note="H->A: Decreased antifugal activity of
FT                   His3-(20-43)-peptide against C. albicans in the presense of
FT                   copper."
FT                   /evidence="ECO:0000269|PubMed:28763199"
FT   MUTAGEN         26..27
FT                   /note="HH->AA: Loss of antifugal activity of
FT                   His3-(20-43)-peptide against C. albicans in the presense of
FT                   copper."
FT                   /evidence="ECO:0000269|PubMed:28763199"
FT   MUTAGEN         30
FT                   /note="K->R: Decreased proteolysis of His3-(20-43)-peptide
FT                   by C. albicans SAP2 and SAP9; when associated with R-36.
FT                   Increased antifugal activity of His3-(20-43)-peptide
FT                   against C. albicans; when associated with R-36."
FT                   /evidence="ECO:0000269|PubMed:31675138"
FT   MUTAGEN         31
FT                   /note="R->I: No effect on candidacidal activity of
FT                   His3-(20-43)-peptide."
FT                   /evidence="ECO:0000269|PubMed:8945538"
FT   MUTAGEN         32
FT                   /note="K->E: Increased proteolysis of His3-(20-43)-peptide
FT                   by C. albicans SAP9. No susceptibility to C. albicans SAP2.
FT                   Decreased antifugal activity of His3-(20-43)-peptide
FT                   against C. albicans."
FT                   /evidence="ECO:0000269|PubMed:31675138,
FT                   ECO:0000269|PubMed:8945538"
FT   MUTAGEN         32
FT                   /note="K->H: Increased proteolysis of His3-(20-43)-peptide
FT                   by C. albicans SAP9. No susceptibility to C. albicans SAP2.
FT                   No change in antifugal activity of His3-(20-43)-peptide
FT                   against C. albicans."
FT                   /evidence="ECO:0000269|PubMed:31675138"
FT   MUTAGEN         32
FT                   /note="K->T: 3-fold reduction in candidacidal activity of
FT                   His3-(20-43)-peptide."
FT                   /evidence="ECO:0000269|PubMed:8945538"
FT   MUTAGEN         35
FT                   /note="E->L: Increased proteolysis of His3-(20-43)-peptide
FT                   by C. albicans SAP2 and SAP9. Increased antifugal activity
FT                   of His3-(20-43)-peptide against C. albicans."
FT                   /evidence="ECO:0000269|PubMed:31675138"
FT   MUTAGEN         35
FT                   /note="E->R: Decreased proteolysis of His3-(20-43)-peptide
FT                   by C. albicans SAP2; increased proteolysis by C. albicans
FT                   SAP9. Increased antifugal activity of His3-(20-43)-peptide
FT                   against C. albicans."
FT                   /evidence="ECO:0000269|PubMed:31675138"
FT   MUTAGEN         36
FT                   /note="K->N: No effect on candidacidal activity of
FT                   His3-(20-43)-peptide."
FT                   /evidence="ECO:0000269|PubMed:8945538"
FT   MUTAGEN         36
FT                   /note="K->R: Decreased proteolysis of His3-(20-43)-peptide
FT                   by C. albicans SAP2 and SAP9; when associated with R-30.
FT                   Increased antifugal activity of His3-(20-43)-peptide
FT                   against C. albicans; when associated with R-30."
FT                   /evidence="ECO:0000269|PubMed:31675138"
FT   MUTAGEN         37..38
FT                   /note="HH->AA: No change in antifugal activity of
FT                   His3-(20-43)-peptide against C. albicans in the presense of
FT                   copper."
FT                   /evidence="ECO:0000269|PubMed:28763199"
FT   MUTAGEN         38
FT                   /note="H->P: No effect on candidacidal activity of
FT                   His3-(20-43)-peptide."
FT                   /evidence="ECO:0000269|PubMed:8945538"
FT   MUTAGEN         40
FT                   /note="H->L,R: No effect on candidacidal activity of
FT                   His3-(20-43)-peptide."
FT                   /evidence="ECO:0000269|PubMed:8945538"
FT   MUTAGEN         41
FT                   /note="R->G: 10-fold reduction in candidacidal activity of
FT                   His3-(20-43)-peptide; when associated with E-32."
FT                   /evidence="ECO:0000269|PubMed:8945538"
SQ   SEQUENCE   51 AA;  6149 MW;  AFCCB4B32083FD65 CRC64;
     MKFFVFALIL ALMLSMTGAD SHAKRHHGYK RKFHEKHHSH RGYRSNYLYD N
//