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Details on Person UniProt:P15516 HTN3
| Class:Id | ReferenceGeneProduct:56544 |
|---|---|
| _chainChangeLog | signal peptide:1-19 added on Fri February 6 2015;chain:20-51 added on Fri February 6 2015;peptide:20-44 added on Fri February 6 2015;peptide:20-43 added on Fri February 6 2015;peptide:20-32 added on Fri February 6 2015;peptide:20-31 added on Fri February 6 2015;peptide:20-30 added on Fri February 6 2015;peptide:24-32 added on Fri February 6 2015;peptide:24-31 added on Fri February 6 2015;peptide:24-30 added on Fri February 6 2015;peptide:25-32 added on Fri February 6 2015;peptide:25-30 added on Fri February 6 2015;peptide:26-32 added on Fri February 6 2015;peptide:26-31 added on Fri February 6 2015;peptide:26-30 added on Fri February 6 2015;peptide:31-51 added on Fri February 6 2015;peptide:31-44 added on Fri February 6 2015;peptide:31-43 added on Fri February 6 2015;peptide:32-44 added on Fri February 6 2015;peptide:32-43 added on Fri February 6 2015;peptide:33-44 added on Fri February 6 2015;peptide:33-43 added on Fri February 6 2015;peptide:34-44 added on Fri February 6 2015;peptide:34-43 added on Fri February 6 2015;peptide:45-51 added on Fri February 6 2015;peptide:47-51 added on Fri February 6 2015;peptide:48-51 added on Fri February 6 2015 |
| _displayName | UniProt:P15516 HTN3 |
| _timestamp | 2025-05-21 21:24:37 |
| chain | signal peptide:1-19 chain:20-51 peptide:20-44 peptide:20-43 peptide:20-32 peptide:20-31 peptide:20-30 peptide:24-32 peptide:24-31 peptide:24-30 peptide:25-32 peptide:25-30 peptide:26-32 peptide:26-31 peptide:26-30 peptide:31-51 peptide:31-44 peptide:31-43 peptide:32-44 peptide:32-43 peptide:33-44 peptide:33-43 peptide:34-44 peptide:34-43 peptide:45-51 peptide:47-51 peptide:48-51 |
| checksum | AFCCB4B32083FD65 |
| comment | 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).FUNCTION 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).FUNCTION 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).ACTIVITY REGULATION 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).SUBUNIT Homodimer (PubMed:12761219). Interacts with HSPA8; the interaction increases binding affinity of HSPA8 to CDKN1B (PubMed:26775844).SUBUNIT Homodimer (PubMed:12761219, PubMed:32751915). Interacts with Candida albicans SSA1 and SSA2 proteins (PubMed:12761219).INTERACTION Secreted by serous acinar and demilune cells.SUBCELLULAR LOCATION 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).DOMAIN The ATCUN motif mediates Cu(2+) binding and the Bis-His motif mediates Cu(1+) binding and are necessary for antifungal activity (PubMed:11226423, PubMed:28763199). The HExxH motif mediates binding to Zin(2+) which is important for the stabilization of a helical conformation in a hydrophobic environment, Hst5 dimerization and antifungal activity (PubMed:10423240, PubMed:11226423, PubMed:32751915).PTM 24 proteolytic products are found in saliva.POLYMORPHISM There are two alleles of HTN3, HIS2(1) (shown here) and HIS2(2) 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 (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.MISCELLANEOUS Proteolytically cleaved by C. albicans SAP proteases with the decreased cleavage rate order of SAP2>SAP9>SAP3>SAP7>SAP4>SAP1>SAP8, leading to Hst 5 degradation and antifungal activity inactivation (PubMed:27390786, PubMed:31675138). Histatin 1, histatin 3 and histatin 5 constitute more than 80% of the total histatin concentration (Probable).SIMILARITY Belongs to the histatin/statherin family.CAUTION Hst 5 uptake into the pathogen cell by direct transfer across the membrane causing cell death has been questioned (PubMed:20487276). Moreover, endocytic vacuolar uptake was showed to be insignificant in terms of Hst 5 toxicity (PubMed:20487276).ONLINE INFORMATION Mouths, enemies and spit - Issue 268 of April 2024 |
| description | recommendedName: Histatin-3 alternativeName: Basic histidine-rich protein shortName: Hst alternativeName: fullName evidence="33"Histatin 3 shortName evidence="32"Hst 3 alternativeName: Histidine-rich protein 3 alternativeName: PB component recommendedName: Histatin-3 /component component recommendedName: His3-(20-44)-peptide shortName: His3 20/44 alternativeName: fullName evidence="33"His3-(1-25)-peptide shortName evidence="33"His3 1/25 alternativeName: fullName evidence="33"Histatin 6 alternativeName: Histatin-3 1/25 alternativeName: Histatin-6 /component component recommendedName: His3-(20-43)-peptide shortName: His3 20/43 alternativeName: fullName evidence="33"His3-(1-24)-peptide shortName evidence="33"His3 1/24 alternativeName: fullName evidence="33"Histatin 5 shortName evidence="32"Hst 5 alternativeName: Histatin-3 1/24 alternativeName: fullName evidence="34"Histatin-5 /component component recommendedName: His3-(20-32)-peptide shortName: His3 20/32 alternativeName: His3-(1-13)-peptide shortName: His3 1/13 alternativeName: Histatin-3 1/13 /component component recommendedName: His3-(20-31)-peptide shortName: His3 20/31 alternativeName: His3-(1-12)-peptide shortName: His3 1/12 alternativeName: Histatin-3 1/12 /component component recommendedName: His3-(20-30)-peptide shortName: His3 20/30 alternativeName: His3-(1-11)-peptide shortName: His3 1/11 alternativeName: Histatin-3 1/11 /component component recommendedName: His3-(24-32)-peptide shortName: His3 24/32 alternativeName: His3-(5-13)-peptide shortName: His3 5/13 alternativeName: Histatin-3 5/13 /component component recommendedName: His3-(24-31)-peptide shortName: His3 24/31 alternativeName: fullName evidence="33"His3-(5-12)-peptide shortName evidence="33"His3 5/12 alternativeName: fullName evidence="33"Histatin 11 alternativeName: Histatin-11 alternativeName: Histatin-3 5/12 /component component recommendedName: His3-(24-30)-peptide shortName: His3 24/30 alternativeName: fullName evidence="33"His3-(5-11)-peptide shortName evidence="33"His3 5/11 alternativeName: fullName evidence="33"Histatin 12 alternativeName: Histatin-12 alternativeName: Histatin-3 5/11 /component component recommendedName: His3-(25-32)-peptide shortName: His3 25/32 alternativeName: His3-(6-13)-peptide shortName: His3 6/13 alternativeName: Histatin-3 6/13 /component component recommendedName: His3-(25-30)-peptide shortName: His3 25/30 alternativeName: His3-(6-11)-peptide shortName: His3 6/11 alternativeName: Histatin-3 6/11 /component component recommendedName: His3-(26-32)-peptide shortName: His3 26/32 alternativeName: His3-(7-13)-peptide shortName: His3 7/13 alternativeName: Histatin-3 7/13 /component component recommendedName: His3-(26-31)-peptide shortName: His3 26/31 alternativeName: His3-(7-12)-peptide shortName: His3 7/12 alternativeName: Histatin-3 7/12 /component component recommendedName: His3-(26-30)-peptide shortName: His3 26/30 alternativeName: His3-(7-11)-peptide shortName: His3 7/11 alternativeName: Histatin-3 7/11 /component component recommendedName: His3-(31-51)-peptide shortName: His3 31/51 alternativeName: fullName evidence="33"His3-(12-32)-peptide shortName evidence="33"His3 12/32 alternativeName: fullName evidence="33"Histatin 4 alternativeName: Histatin-3 12/32 alternativeName: Histatin-4 /component component recommendedName: His3-(31-44)-peptide shortName: His3 31/44 alternativeName: fullName evidence="33"His3-(12-25)-peptide shortName evidence="33"His3 12/25 alternativeName: fullName evidence="33"Histatin 9 alternativeName: Histatin-3 12/25 alternativeName: Histatin-9 /component component recommendedName: His3-(31-43)-peptide shortName: His3 31/43 alternativeName: fullName evidence="33"His3-(12-24)-peptide shortName evidence="33"His3 12/24 alternativeName: fullName evidence="33"Histatin 7 alternativeName: Histatin-3 12/24 alternativeName: Histatin-7 /component component recommendedName: His3-(32-44)-peptide shortName: His3 32/44 alternativeName: fullName evidence="33"His3-(13-25)-peptide shortName evidence="33"His3 13/25 alternativeName: fullName evidence="33"Histatin 10 alternativeName: Histatin-10 alternativeName: Histatin-3 13/25 /component component recommendedName: His3-(32-43)-peptide shortName: His3 32-43 alternativeName: fullName evidence="33"His3-(13-24)-peptide shortName evidence="33"His3 13/24 alternativeName: fullName evidence="33"Histatin 8 alternativeName: Histatin-3 13/24 alternativeName: Histatin-8 /component component recommendedName: His3-(33-44)-peptide shortName: His3 33/44 alternativeName: His3-(14-25)-peptide shortName: His3 14/25 alternativeName: Histatin-3 14/25 /component component recommendedName: His3-(33-43)-peptide shortName: His3 33/43 alternativeName: His3-(14-24)-peptide shortName: His3 14/24 alternativeName: Histatin-3 14/24 /component component recommendedName: His3-(34-44)-peptide shortName: His3 34/44 alternativeName: His3-(15-25)-peptide shortName: His3 15/25 alternativeName: Histatin-3 15/25 /component component recommendedName: His3-(34-43)-peptide shortName: His3 34/43 alternativeName: His3-(15-24)-peptide shortName: His3 15/24 alternativeName: Histatin-3 15/24 /component component recommendedName: His3-(45-51)-peptide shortName: His3 45/51 alternativeName: His3-(26-32)-peptide shortName: His3 26/32 alternativeName: Histatin-3 26/32 /component component recommendedName: His3-(47-51)-peptide shortName: His3 47/51 alternativeName: His3-(28-32)-peptide shortName: His3 28/32 alternativeName: Histatin-3 28/32 /component component recommendedName: His3-(48-51)-peptide shortName: His3 48/51 alternativeName: His3-(29-32)-peptide shortName: His3 29/32 alternativeName: Histatin-3 29/32 /component |
| geneName | HTN3 HIS2 |
| identifier | P15516 |
| isSequenceChanged | FALSE |
| keyword | Antibiotic Antimicrobial Biomineralization Cleavage on pair of basic residues Direct protein sequencing Fungicide Immunity Innate immunity Metal-binding Mitochondrion Proteomics identification Reference proteome Secreted Signal Zinc |
| modified | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8856987] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9688885] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 |
| name | HTN3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8999552] ENSEMBL:ENSG00000205649 HTN3 [Homo sapiens] |
| secondaryIdentifier | HIS3_HUMAN Q16243 Q502Z1 |
| sequenceLength | 51 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:6807136] HTN3(20-43) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:6807183] HTN3 [extracellular region] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P15516 HTN3 (56544)
