Reviewed, UniProtKB/Swiss-Prot P15516 (HIS3_HUMAN)

Names and origin

Protein names

Recommended name:
    Histatin-3
Alternative name(s):
    Histidine-rich protein 3
    PB
    Basic histidine-rich protein
      Short name=Hst
Cleaved into the following 26 chains:
    1- Recommended name:
            Histatin-3
    2- Recommended name:
            Histatin-3 1/25
        Alternative name(s):
            Histatin-6
    3- Recommended name:
            Histatin-3 1/24
        Alternative name(s):
            Histatin-5
    4- Recommended name:
            Histatin-3 1/13
    5- Recommended name:
            Histatin-3 1/12
    6- Recommended name:
            Histatin-3 1/11
    7- Recommended name:
            Histatin-3 5/13
    8- Recommended name:
            Histatin-3 5/12
        Alternative name(s):
            Histatin-11
    9- Recommended name:
            Histatin-3 5/11
        Alternative name(s):
            Histatin-12
    10- Recommended name:
            Histatin-3 6/13
    11- Recommended name:
            Histatin-3 6/11
    12- Recommended name:
            Histatin-3 7/13
    13- Recommended name:
            Histatin-3 7/12
    14- Recommended name:
            Histatin-3 7/11
    15- Recommended name:
            Histatin-3 12/32
        Alternative name(s):
            Histatin-4
    16- Recommended name:
            Histatin-3 12/25
        Alternative name(s):
            Histatin-9
    17- Recommended name:
            Histatin-3 12/24
        Alternative name(s):
            Histatin-7
    18- Recommended name:
            Histatin-3 13/25
        Alternative name(s):
            Histatin-10
    19- Recommended name:
            Histatin-3 13/24
        Alternative name(s):
            Histatin-8
    20- Recommended name:
            Histatin-3 14/25
    21- Recommended name:
            Histatin-3 14/24
    22- Recommended name:
            Histatin-3 15/25
    23- Recommended name:
            Histatin-3 15/24
    24- Recommended name:
            Histatin-3 26/32
    25- Recommended name:
            Histatin-3 28/32
    26- Recommended name:
            Histatin-3 29/32

Gene names

Name:	HTN3
Synonyms:	HIS2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	51 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Histatin-3 1/24 (histatin-5) is especially effective against C.albicans and C.neoformans, and inhibits Lys-gingipain and Arg-gingipain (rgpB) from P.gingivalis. In addition, histatin-3 1/24 is a potent inhibitor of metalloproteinases MMP2 and MMP9. Ref.10 Ref.12
Subunit structure	Histatin-3 1/24 is a homodimer. Histatin-3 and histatin-3 1/24 5 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.
Sequence similarities	Belongs to the histatin/statherin family.

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Metal-binding
Molecular function	Antibiotic Antimicrobial Fungicide
PTM	Cleavage on pair of basic residues Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	biomineral formation Inferred from electronic annotation. Source: UniProtKB-KW defense response to bacterium Ref.4 Ref.7 Non-traceable author statement. Source: UniProtKB defense response to fungus Inferred from electronic annotation. Source: UniProtKB-KW killing of cells of another organism Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Ref.4 Ref.7 Non-traceable author statement. Source: UniProtKB
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MUC7	Q8TAX7	1	EBI-738783,EBI-738582

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Ref.7 Ref.8 Ref.9
	Peptide	20 – 51	32	Histatin-3 Ref.7		PRO_0000021418
	Peptide	20 – 44	25	Histatin-3 1/25		PRO_0000021419
	Peptide	20 – 43	24	Histatin-3 1/24		PRO_0000021420
	Peptide	20 – 32	13	Histatin-3 1/13 Ref.9		PRO_0000021421
	Peptide	20 – 31	12	Histatin-3 1/12		PRO_0000021422
	Peptide	20 – 30	11	Histatin-3 1/11		PRO_0000021423
	Peptide	24 – 32	9	Histatin-3 5/13		PRO_0000021424
	Peptide	24 – 31	8	Histatin-3 5/12		PRO_0000021425
	Peptide	24 – 30	7	Histatin-3 5/11		PRO_0000021426
	Peptide	25 – 32	8	Histatin-3 6/13		PRO_0000021427
	Peptide	25 – 30	6	Histatin-3 6/11		PRO_0000021428
	Peptide	26 – 32	7	Histatin-3 7/13		PRO_0000021429
	Peptide	26 – 31	6	Histatin-3 7/12		PRO_0000021430
	Peptide	26 – 30	5	Histatin-3 7/11		PRO_0000021431
	Peptide	31 – 51	21	Histatin-3 12/32		PRO_0000021432
	Peptide	31 – 44	14	Histatin-3 12/25		PRO_0000021433
	Peptide	31 – 43	13	Histatin-3 12/24		PRO_0000021434
	Peptide	32 – 44	13	Histatin-3 13/25		PRO_0000021435
	Peptide	32 – 43	12	Histatin-3 13/24		PRO_0000021436
	Peptide	33 – 44	12	Histatin-3 14/25		PRO_0000021437
	Peptide	33 – 43	11	Histatin-3 14/24		PRO_0000021438
	Peptide	34 – 44	11	Histatin-3 15/25		PRO_0000021439
	Peptide	34 – 43	10	Histatin-3 15/24		PRO_0000021440
	Peptide	45 – 51	7	Histatin-3 26/32		PRO_0000021441
	Peptide	47 – 51	5	Histatin-3 28/32		PRO_0000021442
	Peptide	48 – 51	4	Histatin-3 29/32		PRO_0000021443
Sites
	Metal binding	34	1	Zinc
	Site	32	1	Important for candidacidal activity
	Site	41	1	Important for candidacidal activity
	Site	43	1	Not sulfated
	Site	47	1	Not sulfated
	Site	49	1	Not sulfated
Natural variations
	Natural variant	41	1	R → Q in histatin-3-2; loss of the proteolytic cleavage site. dbSNP rs1136511. Ref.6		VAR_005288
	Natural variant	47 – 51	5	Missing in histatin-3-2. dbSNP rs17147990.		VAR_005289
Experimental info
	Mutagenesis	31	1	R → I: No effect on candidacidal activity of histatin-3 1/24. Ref.10
	Mutagenesis	32	1	K → T or E: 3-fold reduction in candidacidal activity of histatin-3 1/24. Ref.10
	Mutagenesis	36	1	K → N: No effect on candidacidal activity of histatin-3 1/24. Ref.10
	Mutagenesis	38	1	H → P: No effect on candidacidal activity of histatin-3 1/24. Ref.10
	Mutagenesis	40	1	H → L or R: No effect on candidacidal activity of histatin-3 1/24. Ref.10
	Mutagenesis	41	1	R → G: 10-fold reduction in candidacidal activity of histatin-3 1/24; when associated with E-32. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P15516-1 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: AFCCB4B32083FD65	FASTA	51	6,149
	10 20 30 40 50 MKFFVFALIL ALMLSMTGAD SHAKRHHGYK RKFHEKHHSH RGYRSNYLYD N

References

	« Hide 'large scale' referencesShow '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: 2719677] [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: 3426601] [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: 2344289] [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: 8336540] [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: 15489334] [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: 7951254] [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: 3286634] [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: 2372245] [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: 15272024] [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: 8945538] [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: 11226423] [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: 11179305] [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: 12761219] [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: 14966203] [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: 17503797] [Abstract] Cited for: LACK OF SULFATION AT TYR-43; TYR-47 AND TYR-49, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00012026.
PIR	B32541.
RefSeq	NP_000191.1.
UniGene	Hs.654442
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P15516. 1 interaction.
STRING	P15516.
Protein family/group databases
TCDB	1.C.79.1.1. channel-forming histatin antimicrobial peptide (Histatin) family.
Proteomic databases
PRIDE	P15516.
Genome annotation databases
Ensembl	ENST00000381057; ENSP00000370445; ENSG00000205649; Homo sapiens. [Genome view]
GeneID	3347.
KEGG	hsa:3347.
UCSC	uc003hew.1. human.
Organism-specific databases
CTD	3347.
GeneCards	GC04P070942.
H-InvDB	HIX0004259.
HGNC	HGNC:5284. HTN3.
MIM	142702. gene.
PharmGKB	PA29547.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG100446.
HOVERGEN	P15516.
InParanoid	P15516.
OMA	YKRKFHE.
Gene expression databases
ArrayExpress	P15516.
Bgee	P15516.
CleanEx	HS_HTN3.
Genevestigator	P15516.
GermOnline	ENSG00000205649. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other Resources
NextBio	13240.
SOURCE	Search...

Entry information

Entry name

HIS3_HUMAN

Accession

Primary (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:	December 15, 2009
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.