STAT_HUMAN
ID STAT_HUMAN Reviewed; 62 AA.
AC P02808; A6NKE9; B2R4F8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Statherin;
DE Flags: Precursor;
GN Name=STATH;
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] (ISOFORM 1).
RX PubMed=3502720;
RA Sabatinai L., Carlock L., Johnson G., Azen E.;
RT "cDNA cloning and chromosomal localization (4q11-13) of a gene for
RT statherin, a regulator of calcium in saliva.";
RL Am. J. Hum. Genet. 41:1048-1060(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [GENOMIC DNA].
RX PubMed=2373369; DOI=10.1016/0378-1119(90)90012-g;
RA Sabatini L.M., He Y.-Z., Azen E.A.;
RT "Structure and sequence determination of the gene encoding human salivary
RT statherin.";
RL Gene 89:245-251(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [8]
RP PROTEIN SEQUENCE OF 20-62 (ISOFORM 1), AND PHOSPHORYLATION AT SER-21 AND
RP SER-22.
RX PubMed=838735; DOI=10.1016/s0021-9258(17)40603-x;
RA Schlesinger D.H., Hay D.I.;
RT "Complete covalent structure of statherin, a tyrosine-rich acidic peptide
RT which inhibits calcium phosphate precipitation from human parotid saliva.";
RL J. Biol. Chem. 252:1689-1695(1977).
RN [9]
RP PROTEIN SEQUENCE OF 20-62 (ISOFORMS 1 AND 2), VARIANT PHE-62 DEL, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=1663737; DOI=10.1016/0003-9969(91)90147-m;
RA Jensen J.L., Lamkin M.S., Troxler R.F., Oppenheim F.G.;
RT "Multiple forms of statherin in human salivary secretions.";
RL Arch. Oral Biol. 36:529-534(1991).
RN [10]
RP PARTIAL PROTEIN SEQUENCE OF 1-16.
RX PubMed=3476566; DOI=10.1177/00220345870660021301;
RA Oppenheim F.G., Hay D.I., Smith D.J., Offner G.D., Troxler R.F.;
RT "Molecular basis of salivary proline-rich protein and peptide synthesis:
RT cell-free translations and processing of human and macaque statherin mRNAs
RT and partial amino acid sequence of their signal peptides.";
RL J. Dent. Res. 66:462-466(1987).
RN [11]
RP PROTEIN SEQUENCE OF 20-62 (ISOFORM 1), AND SULFATION.
RX PubMed=17389930; DOI=10.7150/ijbs.3.237;
RA Kasinathan C., Gandhi N., Ramaprasad P., Sundaram P., Ramasubbu N.;
RT "Tyrosine sulfation of statherin.";
RL Int. J. Biol. Sci. 3:237-241(2007).
RN [12]
RP TRANSGLUTAMINATION, AND MASS SPECTROMETRY.
RX PubMed=17313100; DOI=10.1002/jssc.200600244;
RA Cabras T., Inzitari R., Fanali C., Scarano E., Patamia M., Sanna M.T.,
RA Pisano E., Giardina B., Castagnola M., Messana I.;
RT "HPLC-MS characterization of cyclo-statherin Q-37, a specific cyclization
RT product of human salivary statherin generated by transglutaminase 2.";
RL J. Sep. Sci. 29:2600-2608(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Salivary protein that stabilizes saliva supersaturated with
CC calcium salts by inhibiting the precipitation of calcium phosphate
CC salts. It also modulates hydroxyapatite crystal formation on the tooth
CC surface.
CC -!- INTERACTION:
CC P02808; Q13520: AQP6; NbExp=3; IntAct=EBI-738687, EBI-13059134;
CC P02808; Q96Q80: DERL3; NbExp=3; IntAct=EBI-738687, EBI-12831318;
CC P02808; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-738687, EBI-781551;
CC P02808; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-738687, EBI-18304435;
CC P02808; Q96P31-6: FCRL3; NbExp=3; IntAct=EBI-738687, EBI-17443171;
CC P02808; Q96LL3: FIMP; NbExp=3; IntAct=EBI-738687, EBI-12887376;
CC P02808; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-738687, EBI-13345167;
CC P02808; O15529: GPR42; NbExp=3; IntAct=EBI-738687, EBI-18076404;
CC P02808; P48051: KCNJ6; NbExp=3; IntAct=EBI-738687, EBI-12017638;
CC P02808; A8MZ59: LEUTX; NbExp=3; IntAct=EBI-738687, EBI-17490413;
CC P02808; Q6N075: MFSD5; NbExp=3; IntAct=EBI-738687, EBI-3920969;
CC P02808; Q6IN84: MRM1; NbExp=3; IntAct=EBI-738687, EBI-5454865;
CC P02808; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-738687, EBI-3923617;
CC P02808; Q8TAX7: MUC7; NbExp=2; IntAct=EBI-738687, EBI-738582;
CC P02808; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-738687, EBI-7545592;
CC P02808; O95470: SGPL1; NbExp=3; IntAct=EBI-738687, EBI-1046170;
CC P02808; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-738687, EBI-18159983;
CC P02808; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-738687, EBI-12898013;
CC P02808; Q6ZMD2-2: SPNS3; NbExp=3; IntAct=EBI-738687, EBI-17848320;
CC P02808; Q00059: TFAM; NbExp=3; IntAct=EBI-738687, EBI-1049924;
CC P02808; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-738687, EBI-12947623;
CC P02808; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-738687, EBI-11742770;
CC P02808; Q9Y320: TMX2; NbExp=3; IntAct=EBI-738687, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Both isoforms can occur with the Phe-62 deletion.;
CC Name=1;
CC IsoId=P02808-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P02808-2; Sequence=VSP_045744;
CC -!- TISSUE SPECIFICITY: Secreted by parotid and submandibular glands.
CC -!- PTM: Substrate for transglutaminase-2. More than 95% of the cyclized
CC peptide is cyclo-statherin Q-37, and less than 5% is cyclo-statherin Q-
CC 39. Cyclized forms account for about 1% of total statherin in saliva.
CC {ECO:0000269|PubMed:17313100}.
CC -!- PTM: Sulfated on tyrosine residues. {ECO:0000269|PubMed:17389930}.
CC -!- MASS SPECTROMETRY: Mass=5380.0; Mass_error=0.3; Method=Electrospray;
CC Note=With phosphorylated Ser-21 and Ser-22.;
CC Evidence={ECO:0000269|PubMed:17313100};
CC -!- MASS SPECTROMETRY: Mass=5363.0; Mass_error=0.3; Method=Electrospray;
CC Note=With phosphorylated Ser-21 and Ser-22 and transglutamine cross-
CC link.; Evidence={ECO:0000269|PubMed:17313100};
CC -!- SIMILARITY: Belongs to the histatin/statherin family. {ECO:0000305}.
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DR EMBL; M18078; AAA60594.1; -; mRNA.
DR EMBL; M18371; AAA60600.1; -; mRNA.
DR EMBL; M32639; AAA60593.1; -; Genomic_DNA.
DR EMBL; AK311812; BAG34755.1; -; mRNA.
DR EMBL; AC063956; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX05604.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX05605.1; -; Genomic_DNA.
DR EMBL; BC067219; AAH67219.1; -; mRNA.
DR CCDS; CCDS33998.1; -. [P02808-2]
DR CCDS; CCDS3533.1; -. [P02808-1]
DR PIR; JH0153; SBHUP.
DR RefSeq; NP_001009181.1; NM_001009181.1. [P02808-2]
DR RefSeq; NP_003145.1; NM_003154.2. [P02808-1]
DR AlphaFoldDB; P02808; -.
DR BioGRID; 112656; 45.
DR IntAct; P02808; 32.
DR MINT; P02808; -.
DR STRING; 9606.ENSP00000246895; -.
DR TCDB; 1.C.79.1.2; the channel-forming histatin antimicrobial peptide (histatin) family.
DR iPTMnet; P02808; -.
DR PhosphoSitePlus; P02808; -.
DR BioMuta; STATH; -.
DR EPD; P02808; -.
DR MassIVE; P02808; -.
DR MaxQB; P02808; -.
DR PaxDb; P02808; -.
DR PeptideAtlas; P02808; -.
DR PRIDE; P02808; -.
DR ProteomicsDB; 51602; -. [P02808-1]
DR TopDownProteomics; P02808-1; -. [P02808-1]
DR TopDownProteomics; P02808-2; -. [P02808-2]
DR Antibodypedia; 44306; 68 antibodies from 16 providers.
DR DNASU; 6779; -.
DR Ensembl; ENST00000246895.9; ENSP00000246895.4; ENSG00000126549.11. [P02808-1]
DR Ensembl; ENST00000381060.2; ENSP00000370448.2; ENSG00000126549.11. [P02808-2]
DR Ensembl; ENST00000634727.1; ENSP00000489107.1; ENSG00000282891.4. [P02808-2]
DR Ensembl; ENST00000635686.2; ENSP00000489243.1; ENSG00000282891.4. [P02808-1]
DR Ensembl; ENST00000676772.1; ENSP00000503126.1; ENSG00000282891.4. [P02808-1]
DR GeneID; 6779; -.
DR KEGG; hsa:6779; -.
DR MANE-Select; ENST00000246895.9; ENSP00000246895.4; NM_003154.3; NP_003145.1.
DR UCSC; uc003heu.2; human. [P02808-1]
DR CTD; 6779; -.
DR DisGeNET; 6779; -.
DR GeneCards; STATH; -.
DR HGNC; HGNC:11369; STATH.
DR HPA; ENSG00000126549; Tissue enriched (salivary).
DR MIM; 184470; gene.
DR neXtProt; NX_P02808; -.
DR OpenTargets; ENSG00000126549; -.
DR PharmGKB; PA36187; -.
DR VEuPathDB; HostDB:ENSG00000126549; -.
DR eggNOG; ENOG502TD50; Eukaryota.
DR GeneTree; ENSGT00940000164572; -.
DR HOGENOM; CLU_208169_0_0_1; -.
DR InParanoid; P02808; -.
DR OMA; CIQERRY; -.
DR OrthoDB; 1640595at2759; -.
DR PhylomeDB; P02808; -.
DR TreeFam; TF341588; -.
DR PathwayCommons; P02808; -.
DR SignaLink; P02808; -.
DR BioGRID-ORCS; 6779; 12 hits in 1055 CRISPR screens.
DR ChiTaRS; STATH; human.
DR GeneWiki; STATH; -.
DR GenomeRNAi; 6779; -.
DR Pharos; P02808; Tbio.
DR PRO; PR:P02808; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P02808; protein.
DR Bgee; ENSG00000126549; Expressed in olfactory segment of nasal mucosa and 70 other tissues.
DR Genevisible; P02808; HS.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0030197; F:extracellular matrix constituent, lubricant activity; NAS:UniProtKB.
DR GO; GO:0046848; F:hydroxyapatite binding; NAS:UniProtKB.
DR GO; GO:0030345; F:structural constituent of tooth enamel; NAS:UniProtKB.
DR GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:InterPro.
DR GO; GO:0030502; P:negative regulation of bone mineralization; NAS:UniProtKB.
DR GO; GO:0001503; P:ossification; TAS:ProtInc.
DR GO; GO:0046541; P:saliva secretion; NAS:UniProtKB.
DR DisProt; DP02207; -.
DR InterPro; IPR030773; Histatin/statherin.
DR InterPro; IPR005575; Statherin.
DR PANTHER; PTHR15057; PTHR15057; 1.
DR Pfam; PF03875; Statherin; 1.
DR PIRSF; PIRSF002565; Statherin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Biomineralization; Direct protein sequencing;
KW Isopeptide bond; Phosphoprotein; Reference proteome; Secreted; Signal;
KW Sulfation.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:3476566"
FT CHAIN 20..62
FT /note="Statherin"
FT /id="PRO_0000022422"
FT REGION 20..25
FT /note="Hydroxyapatite-binding; inhibits crystal growth"
FT REGION 38..62
FT /note="Hydrophobic; inhibits precipitation of calcium
FT phosphate salts"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:838735"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:838735"
FT CROSSLNK 25..58
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln); in form
FT cyclo-statherin Q-39"
FT CROSSLNK 25..56
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln); in form
FT cyclo-statherin Q-37"
FT VAR_SEQ 25..34
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_045744"
FT VARIANT 62
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:1663737"
FT /id="VAR_069065"
SQ SEQUENCE 62 AA; 7304 MW; CFE32EC235CA3A22 CRC64;
MKFLVFAFIL ALMVSMIGAD SSEEKFLRRI GRFGYGYGPY QPVPEQPLYP QPYQPQYQQY
TF
