P02808 (STAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Statherin

Gene names

Name:

STATH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	62 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	Salivary protein that stabilizes saliva supersaturated with calcium salts by inhibiting the precipitation of calcium phosphate salts. It also modulates hydroxyapatite crystal formation on the tooth surface.
Subcellular location	Secreted.
Tissue specificity	Secreted by parotid and submandibular glands.
Post-translational modification	Substrate for transglutaminase-2. More than 95% of the cyclized peptide is cyclo-statherin Q-37, and less than 5% is cyclo-statherin Q-39. Cyclized forms account for about 1% of total statherin in saliva. Sulfated on tyrosine residues.
Sequence similarities	Belongs to the histatin/statherin family.
Mass spectrometry	Molecular mass is 5380.0±0.3 Da from positions 20 - 62. Determined by ESI. With phosphorylated Ser-21 and Ser-22. Ref.12 Molecular mass is 5363.0±0.3 Da from positions 20 - 62. Determined by ESI. With phosphorylated Ser-21 and Ser-22 and transglutamine cross-link. Ref.12

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
PTM	Isopeptide bond Phosphoprotein Sulfation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	biomineral tissue development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of bone mineralization Non-traceable author statement PubMed 1313424. Source: UniProtKB ossification Traceable author statement PubMed 1313424. Source: ProtInc saliva secretion Non-traceable author statement PubMed 1718282. Source: UniProtKB
Cellular_component	extracellular region Non-traceable author statement PubMed 1718282. Source: UniProtKB
Molecular_function	extracellular matrix constituent, lubricant activity Non-traceable author statement PubMed 1718282. Source: UniProtKB hydroxyapatite binding Non-traceable author statement PubMed 1741693. Source: UniProtKB structural constituent of tooth enamel Non-traceable author statement PubMed 1718282. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MUC7	Q8TAX7	2	EBI-738687,EBI-738582

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Both isoforms can occur with the Phe-62 deletion.

Isoform 1 (identifier: P02808-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P02808-2)

The sequence of this isoform differs from the canonical sequence as follows:
     25-34: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Ref.8 Ref.9 Ref.10 Ref.11
	Chain	20 – 62	43	Statherin		PRO_0000022422
Regions
	Region	20 – 25	6	Hydroxyapatite-binding; inhibits crystal growth
	Region	38 – 62	25	Hydrophobic; inhibits precipitation of calcium phosphate salts
Amino acid modifications
	Modified residue	21	1	Phosphoserine Ref.8
	Modified residue	22	1	Phosphoserine Ref.8
	Cross-link	25 ↔ 58		Isoglutamyl lysine isopeptide (Lys-Gln); in form cyclo-statherin Q-39
	Cross-link	25 ↔ 56		Isoglutamyl lysine isopeptide (Lys-Gln); in form cyclo-statherin Q-37
Natural variations
	Alternative sequence	25 – 34	10	Missing in isoform 2.		VSP_045744
	Natural variant	62	1	Missing. Ref.9		VAR_069065

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: CFE32EC235CA3A22	FASTA	62	7,304
	10 20 30 40 50 60 MKFLVFAFIL ALMVSMIGAD SSEEKFLRRI GRFGYGYGPY QPVPEQPLYP QPYQPQYQQY TF
	Isoform 2 [UniParc]. Checksum: C94F2FE112DAA733	FASTA	52	6,073
	10 20 30 40 50 MKFLVFAFIL ALMVSMIGAD SSEEYGYGPY QPVPEQPLYP QPYQPQYQQY TF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and chromosomal localization (4q11-13) of a gene for statherin, a regulator of calcium in saliva." Sabatinai L., Carlock L., Johnson G., Azen E. Am. J. Hum. Genet. 41:1048-1060(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] (ISOFORM 1).
[3]	"Structure and sequence determination of the gene encoding human salivary statherin." Sabatini L.M., He Y.-Z., Azen E.A. Gene 89:245-251(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Trachea.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1). Tissue: Thyroid.
[8]	"Complete covalent structure of statherin, a tyrosine-rich acidic peptide which inhibits calcium phosphate precipitation from human parotid saliva." Schlesinger D.H., Hay D.I. J. Biol. Chem. 252:1689-1695(1977) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-62 (ISOFORM 1), PHOSPHORYLATION AT SER-21 AND SER-22.
[9]	"Multiple forms of statherin in human salivary secretions." Jensen J.L., Lamkin M.S., Troxler R.F., Oppenheim F.G. Arch. Oral Biol. 36:529-534(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-62 (ISOFORMS 1 AND 2), VARIANT PHE-62 DEL, MASS SPECTROMETRY.
[10]	"Molecular basis of salivary proline-rich protein and peptide synthesis: cell-free translations and processing of human and macaque statherin mRNAs and partial amino acid sequence of their signal peptides." Oppenheim F.G., Hay D.I., Smith D.J., Offner G.D., Troxler R.F. J. Dent. Res. 66:462-466(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 1-16.
[11]	"Tyrosine sulfation of statherin." Kasinathan C., Gandhi N., Ramaprasad P., Sundaram P., Ramasubbu N. Int. J. Biol. Sci. 3:237-241(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-62 (ISOFORM 1), SULFATION.
[12]	"HPLC-MS characterization of cyclo-statherin Q-37, a specific cyclization product of human salivary statherin generated by transglutaminase 2." Cabras T., Inzitari R., Fanali C., Scarano E., Patamia M., Sanna M.T., Pisano E., Giardina B., Castagnola M., Messana I. J. Sep. Sci. 29:2600-2608(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSGLUTAMINATION, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M18078 mRNA. Translation: AAA60594.1. M18371 mRNA. Translation: AAA60600.1. M32639 Genomic DNA. Translation: AAA60593.1. AK311812 mRNA. Translation: BAG34755.1. AC063956 Genomic DNA. No translation available. CH471057 Genomic DNA. Translation: EAX05604.1. CH471057 Genomic DNA. Translation: EAX05605.1. BC067219 mRNA. Translation: AAH67219.1.
IPI	IPI00022990. IPI00550456.
PIR	SBHUP. JH0153.
RefSeq	NP_001009181.1. NM_001009181.1. NP_003145.1. NM_003154.2.
UniGene	Hs.654495.
3D structure databases
ProteinModelPortal	P02808.
ModBase	Search...
Protein-protein interaction databases
IntAct	P02808. 1 interaction.
STRING	9606.ENSP00000246895.
Protein family/group databases
TCDB	1.C.79.1.2. channel-forming histatin antimicrobial peptide (Histatin) family.
PTM databases
PhosphoSite	P02808.
Polymorphism databases
DMDM	134947.
Proteomic databases
PaxDb	P02808.
PeptideAtlas	P02808.
PRIDE	P02808.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000246895; ENSP00000246895; ENSG00000126549. ENST00000381060; ENSP00000370448; ENSG00000126549.
GeneID	6779.
KEGG	hsa:6779.
UCSC	uc003heu.1. human.
Organism-specific databases
CTD	6779.
GeneCards	GC04P070861.
HGNC	HGNC:11369. STATH.
HPA	HPA044569.
MIM	184470. gene.
neXtProt	NX_P02808.
PharmGKB	PA36187.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG255838.
HOGENOM	HOG000293326.
InParanoid	P02808.
KO	K13914.
OMA	HFHSLEN.
OrthoDB	EOG4NKBXC.
Gene expression databases
ArrayExpress	P02808.
Bgee	P02808.
CleanEx	HS_STATH.
Genevestigator	P02808.
GermOnline	ENSG00000126549. Homo sapiens.
Family and domain databases
InterPro	IPR005575. Statherin. [Graphical view]
Pfam	PF03875. Statherin. 1 hit. [Graphical view]
PIRSF	PIRSF002565. Statherin. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	STATH. human.
GenomeRNAi	6779.
NextBio	26462.
SOURCE	Search...

Entry information

Entry name

STAT_HUMAN

Accession

Primary (citable) accession number: P02808
Secondary accession number(s): A6NKE9, B2R4F8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 1, 1989
Last modified:	April 3, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.