HTN3
entrez
3347
canonical
uniprot
P15516
canonical
ensembl
ENSG00000205649
resolver
ensembl
ENSG00000282967
resolver
ensp
ENSP00000432561
resolver
ensp
ENSP00000489520
resolver
ensp
ENSP00000500623
resolver
ensp
ENSP00000500810
resolver
enst
ENST00000530128
resolver
enst
ENST00000635585
resolver
enst
ENST00000672568
resolver
enst
ENST00000673563
resolver
genesymbol
HTN3
resolver
genesymbol_syn
HIS2
resolver
hgnc
HGNC:5284
resolver
uniprot
Q16243
resolver
uniprot
Q502Z1
resolver
uniprot_entry
HIS3_HUMAN
resolver
uniprot_sec
Q16243
resolver
uniprot_sec
Q502Z1
resolver
activity_regulation
ACTIVITY REGULATION: [His3-(20-43)-peptide]: Metal binding such as zinc and copper increases antimicrobial activity (PubMed:19846304, PubMed:28763199, PubMed:32751915). Conjugation with spermidine increases bactericidal efficiency against ESKAPE pathogens (PubMed:28261570). Calcium inhibits antifungal activity against C.albicans at physiological concentrations by disrupting Hst 5 binding with C.albicans (PubMed:12939362). Antifungal activity is also reduced by some salivary ions as Mg(2+), Cl(-) and CO(3-) (PubMed:12939362). Fe(3+) also decreases antifungal activity (PubMed:28763199). Antifungal activity is also decreased at pH above 8 and below 4 (PubMed:12939362). {ECO:0000269|PubMed:12939362, ECO:0000269|PubMed:19846304, ECO:0000269|PubMed:28261570, ECO:0000269|PubMed:28763199, ECO:0000269|PubMed:32751915}.
uniprot
proteins
amino_acid_sequence
MKFFVFALILALMLSMTGADSHAKRHHGYKRKFHEKHHSHRGYRSNYLYDN
uniprot
proteins
function
FUNCTION: Histatins are cationic and histidine-rich peptides mainly found in the saliva of higher primates (PubMed:3286634). They are considered to be major precursors of the protective proteinaceous structure on tooth surfaces (enamel pellicle). Hsts can be divided into two major groups according to their biological functions: antimicrobial Hsts (e.g. Hst 5/HTN3) and cell-activating Hsts (e.g. Hst 1/HTN1, Hst 2/HTN1 and Hst 3/HTN3) (PubMed:32225006). {ECO:0000269|PubMed:32225006, ECO:0000269|PubMed:3286634}.; FUNCTION: [Histatin-3]: Histatin 3 (Hst 3) is mostly involved in cell migration and wound healing in the oral cavity (PubMed:18650243). Also stimulates cell proliferation after binding to heat shock protein HSC70, which enhances HSC70-CDKN1B complex formation and subsequent ubiquitination during G1/S transition (PubMed:26775844). Also displays antifungal activity against pathogenic yeast Candida albicans, however with less effectiveness than Hst 5 (PubMed:11083804, PubMed:3286634). {ECO:0000269|PubMed:11083804, ECO:0000269|PubMed:18650243, ECO:0000269|PubMed:26775844, ECO:0000269|PubMed:3286634}.; FUNCTION: [His3-(20-43)-peptide]: Histatin 5 (Hst 5), a fragment of Hst 3, is the major histatin exhibiting antifungal and antibacterial activities (PubMed:10066791, PubMed:11083804, PubMed:11179305, PubMed:11717389, PubMed:12939362, PubMed:15485849, PubMed:2372245, PubMed:8945538). It is effective against pathogenic yeast C.albicans, C.neoformans, C.glabrata and S.cerevisiae as well as ESKAPE bacterial pathogens (PubMed:18974864, PubMed:23613860, PubMed:2372245, PubMed:28261570, PubMed:8945538). Secreted Hst 5 mediates a multi-step intracellular mechanism of action against the pathogen. Depending on peptide concentration and pathogen, uptake across the membrane can occur through transporters, direct interaction with plasma membrane and/or receptor-mediated endocytosis (PubMed:18974864, PubMed:20487276, PubMed:28261570). Binds C.albicans cell wall proteins SSA1 and SSA2 and glycans in an energy-independent manner, then is taken up by the cells through fungal polyamine transporters DUR3 and DUR31 in an energy-dependent manner (PubMed:12761219, PubMed:20487276, PubMed:22033918, PubMed:23613860). Internalized Hst5 is then targeted to the energized mitochondrion to induce reactive oxygen species (ROS) formation and subsequent release of intracellular non-lytic ATP which ultimately leads to fungal cell death (PubMed:10066791, PubMed:11083804, PubMed:11717389). In addition, inhibits C.albicans TRK1 potassium-transporter which causes exudation of intracellular K(+), generating an osmotic imbalance leading to delayed membrane lysis and cell death (PubMed:15485849). Also acts as a potent inhibitor of bacterial proteases such as Lys-gingipain and Arg-gingipain (rgpB) from P.gingivalis as well as human metalloproteases MMP2 and MMP9 (PubMed:11179305). The binding of metals such as zinc, copper or nickel with Hst 5 results in the protection of the enamel and antimicrobial activities such as the inhibition of microbial growth by decreasing the metal concentration, the formation of ROS commonly associated with redox-active metals, the induction of membrane disruption mediated by zinc binding (PubMed:19846304, PubMed:28261570, PubMed:28763199, PubMed:32751915). Also involved in coating oral surfaces in the form of a salivary film which reduces colonization by C.albicans on epithelial cell surfaces (PubMed:26379655). Secreted Hst 5 can also internalize mammalian epithelial cells and target the mitochondria although it does not exert cytotoxic effects in these cells (PubMed:32225006). In contrast with Hst 3, not able to promote wound healing in mammalian host cells (PubMed:18650243). {ECO:0000269|PubMed:10066791, ECO:0000269|PubMed:11083804, ECO:0000269|PubMed:11179305, ECO:0000269|PubMed:11717389, ECO:0000269|PubMed:12761219, ECO:0000269|PubMed:12939362, ECO:0000269|PubMed:15485849, ECO:0000269|PubMed:18650243, ECO:0000269|PubMed:18974864, ECO:0000269|PubMed:19846304, ECO:0000269|PubMed:20487276, ECO:0000269|PubMed:22033918, ECO:0000269|PubMed:23613860, ECO:0000269|PubMed:2372245, ECO:0000269|PubMed:26379655, ECO:0000269|PubMed:28261570, ECO:0000269|PubMed:28763199, ECO:0000269|PubMed:32225006, ECO:0000269|PubMed:32751915, ECO:0000269|PubMed:8945538}.
uniprot
proteins
mass_dalton
6149
uniprot
proteins
mutagenesis
MUTAGEN 22; /note="H->A: Decreased antifungal activity of His3-(20-43)-peptide against C.albicans in the presense of copper."; /evidence="ECO:0000269|PubMed:28763199"; MUTAGEN 26..27; /note="HH->AA: Loss of antifungal activity of His3-(20-43)-peptide against C.albicans in the presense of copper."; /evidence="ECO:0000269|PubMed:28763199"; MUTAGEN 30; /note="K->R: Decreased proteolysis of His3-(20-43)-peptide by C.albicans SAP2 and SAP9; when associated with R-36. Increased antifungal activity of His3-(20-43)-peptide against C.albicans; when associated with R-36."; /evidence="ECO:0000269|PubMed:31675138"; MUTAGEN 31; /note="R->I: No effect on candidacidal activity of His3-(20-43)-peptide."; /evidence="ECO:0000269|PubMed:8945538"; MUTAGEN 32; /note="K->E: Increased proteolysis of His3-(20-43)-peptide by C.albicans SAP9. No susceptibility to C.albicans SAP2. Decreased antifungal activity of His3-(20-43)-peptide against C.albicans."; /evidence="ECO:0000269|PubMed:31675138, ECO:0000269|PubMed:8945538"; MUTAGEN 32; /note="K->H: Increased proteolysis of His3-(20-43)-peptide by C.albicans SAP9. No susceptibility to C.albicans SAP2. No change in antifungal activity of His3-(20-43)-peptide against C.albicans."; /evidence="ECO:0000269|PubMed:31675138"; MUTAGEN 32; /note="K->T: 3-fold reduction in candidacidal activity of His3-(20-43)-peptide."; /evidence="ECO:0000269|PubMed:8945538"; MUTAGEN 35; /note="E->L: Increased proteolysis of His3-(20-43)-peptide by C.albicans SAP2 and SAP9. Increased antifungal activity of His3-(20-43)-peptide against C.albicans."; /evidence="ECO:0000269|PubMed:31675138"; MUTAGEN 35; /note="E->R: Decreased proteolysis of His3-(20-43)-peptide by C.albicans SAP2; increased proteolysis by C.albicans SAP9. Increased antifungal activity of His3-(20-43)-peptide against C.albicans."; /evidence="ECO:0000269|PubMed:31675138"; MUTAGEN 36; /note="K->N: No effect on candidacidal activity of His3-(20-43)-peptide."; /evidence="ECO:0000269|PubMed:8945538"; MUTAGEN 36; /note="K->R: Decreased proteolysis of His3-(20-43)-peptide by C.albicans SAP2 and SAP9; when associated with R-30. Increased antifungal activity of His3-(20-43)-peptide against C.albicans; when associated with R-30."; /evidence="ECO:0000269|PubMed:31675138"; MUTAGEN 37..38; /note="HH->AA: No change in antifungal activity of His3-(20-43)-peptide against C.albicans in the presense of copper."; /evidence="ECO:0000269|PubMed:28763199"; MUTAGEN 38; /note="H->P: No effect on candidacidal activity of His3-(20-43)-peptide."; /evidence="ECO:0000269|PubMed:8945538"; MUTAGEN 40; /note="H->L,R: No effect on candidacidal activity of His3-(20-43)-peptide."; /evidence="ECO:0000269|PubMed:8945538"; MUTAGEN 41; /note="R->G: 10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32."; /evidence="ECO:0000269|PubMed:8945538
uniprot
proteins
post_translational_modification
PTM: 24 proteolytic products are found in saliva. {ECO:0000269|PubMed:15272024}.
uniprot
proteins
protein_family
Histatin/statherin family
uniprot
proteins
pubmed
10066791
uniprot
proteins
pubmed
10423240
uniprot
proteins
pubmed
11083804
uniprot
proteins
pubmed
11179305
uniprot
proteins
pubmed
11226423
uniprot
proteins
pubmed
11717389
uniprot
proteins
pubmed
12761219
uniprot
proteins
pubmed
12939362
uniprot
proteins
pubmed
14966203
uniprot
proteins
pubmed
15272024
uniprot
proteins
pubmed
15485849
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17503797
uniprot
proteins
pubmed
18650243
uniprot
proteins
pubmed
18974864
uniprot
proteins
pubmed
19846304
uniprot
proteins
pubmed
20487276
uniprot
proteins
pubmed
20973643
uniprot
proteins
pubmed
22033918
uniprot
proteins
pubmed
2344289
uniprot
proteins
pubmed
23613860
uniprot
proteins
pubmed
2372245
uniprot
proteins
pubmed
26379655
uniprot
proteins
pubmed
26775844
uniprot
proteins
pubmed
2719677
uniprot
proteins
pubmed
27390786
uniprot
proteins
pubmed
28261570
uniprot
proteins
pubmed
28763199
uniprot
proteins
pubmed
31675138
uniprot
proteins
pubmed
32225006
uniprot
proteins
pubmed
32751915
uniprot
proteins
pubmed
3286634
uniprot
proteins
pubmed
3426601
uniprot
proteins
pubmed
7951254
uniprot
proteins
pubmed
8336540
uniprot
proteins
pubmed
8945538
uniprot
proteins
sequence_length
51
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14966203}. Note=Secreted by serous acinar and demilune cells. {ECO:0000269|PubMed:14966203}.; SUBCELLULAR LOCATION: [His3-(20-43)-peptide]: Secreted {ECO:0000269|PubMed:14966203}. Mitochondrion {ECO:0000269|PubMed:32225006}. Note=Targeted to mitochondria in pathogen cells after internalization (PubMed:10066791). Also localized in the vacuole in pathogen cells (PubMed:18974864). Also co-localized with mitochondria after internalization in host mammalian cells (PubMed:32225006). {ECO:0000269|PubMed:10066791, ECO:0000269|PubMed:18974864, ECO:0000269|PubMed:32225006}.
uniprot
proteins