ID   CYTN_HUMAN              Reviewed;         141 AA.
AC   P01037; Q96LE6; Q9UCQ6;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 3.
DT   13-FEB-2019, entry version 184.
DE   RecName: Full=Cystatin-SN;
DE   AltName: Full=Cystain-SA-I;
DE   AltName: Full=Cystatin-1;
DE   AltName: Full=Salivary cystatin-SA-1;
DE   Flags: Precursor;
GN   Name=CST1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-4.
RX   PubMed=3446578; DOI=10.1016/0378-1119(87)90196-X;
RA   Saitoh E., Kim H.-S., Smithies O., Maeda N.;
RT   "Human cysteine-proteinase inhibitors: nucleotide sequence analysis of
RT   three members of the cystatin gene family.";
RL   Gene 61:329-338(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HIS-4.
RX   PubMed=2837486;
RA   Al-Hashimi I., Dickinson D.P., Levine M.J.;
RT   "Purification, molecular cloning, and sequencing of salivary cystatin
RT   SA-1.";
RL   J. Biol. Chem. 263:9381-9387(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 21-141.
RX   PubMed=3202964;
RA   Saitoh E., Isemura S., Sanada K., Kim H.-S., Smithies O., Maeda N.;
RT   "Cystatin superfamily. Evidence that family II cystatin genes are
RT   evolutionarily related to family III cystatin genes.";
RL   Biol. Chem. Hoppe-Seyler 369:191-197(1988).
RN   [6]
RP   PROTEIN SEQUENCE OF 21-40.
RC   TISSUE=Saliva;
RX   PubMed=1778989; DOI=10.1093/oxfordjournals.jbchem.a123634;
RA   Isemura S., Saitoh E., Sanada K., Minakata K.;
RT   "Identification of full-sized forms of salivary (S-type) cystatins
RT   (cystatin SN, cystatin SA, cystatin S, and two phosphorylated forms of
RT   cystatin S) in human whole saliva and determination of phosphorylation
RT   sites of cystatin S.";
RL   J. Biochem. 110:648-654(1991).
RN   [7]
RP   PROTEIN SEQUENCE OF 21-32.
RX   PubMed=11788998;
RX   DOI=10.1002/1615-9861(200201)2:1<112::AID-PROT112>3.0.CO;2-N;
RA   Ghafouri B., Stahlbom B., Tagesson C., Lindahl M.;
RT   "Newly identified proteins in human nasal lavage fluid from non-
RT   smokers and smokers using two-dimensional gel electrophoresis and
RT   peptide mass fingerprinting.";
RL   Proteomics 2:112-120(2002).
RN   [8]
RP   PROTEIN SEQUENCE OF 29-141.
RX   PubMed=3514272; DOI=10.1016/0014-5793(86)81201-7;
RA   Isemura S., Saitoh E., Sanada K.;
RT   "Characterization of a new cysteine proteinase inhibitor of human
RT   saliva, cystatin SN, which is immunologically related to cystatin S.";
RL   FEBS Lett. 198:145-149(1986).
RN   [9]
RP   PROTEIN SEQUENCE OF 21-35.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally
RT   verified cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [10]
RP   PROTEIN SEQUENCE OF 105-141, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Tear;
RX   PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA   Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA   Suarez T., Elortza F.;
RT   "Human basal tear peptidome characterization by CID, HCD, and ETD
RT   followed by in silico and in vitro analyses for antimicrobial peptide
RT   identification.";
RL   J. Proteome Res. 14:2649-2658(2015).
RN   [11]
RP   DISULFIDE BONDS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Saliva;
RX   PubMed=20189825; DOI=10.1016/j.jasms.2010.01.025;
RA   Ryan C.M., Souda P., Halgand F., Wong D.T., Loo J.A., Faull K.F.,
RA   Whitelegge J.P.;
RT   "Confident assignment of intact mass tags to human salivary cystatins
RT   using top-down Fourier-transform ion cyclotron resonance mass
RT   spectrometry.";
RL   J. Am. Soc. Mass Spectrom. 21:908-917(2010).
CC   -!- FUNCTION: Human saliva appears to contain several cysteine
CC       proteinase inhibitors that are immunologically related to cystatin
CC       S but that differ in their specificity due to amino acid sequence
CC       differences. Cystatin SN, with a pI of 7.5, is a much better
CC       inhibitor of papain and dipeptidyl peptidase I than is cystatin S,
CC       although both inhibit ficin equally well.
CC   -!- INTERACTION:
CC       O43765:SGTA; NbExp=3; IntAct=EBI-1056240, EBI-347996;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20189825}.
CC   -!- TISSUE SPECIFICITY: Expressed in submandibular and sublingual
CC       saliva but not in parotid saliva (at protein level). Expressed in
CC       saliva, tears, urine and seminal fluid.
CC       {ECO:0000269|PubMed:20189825}.
CC   -!- MASS SPECTROMETRY: Mass=14303.1553; Mass_error=0.0675;
CC       Method=Electrospray; Range=21-141;
CC       Evidence={ECO:0000269|PubMed:20189825};
CC   -!- MASS SPECTROMETRY: Mass=14319.171; Mass_error=0.0523;
CC       Method=Electrospray; Range=21-141; Note=Variant Leu-31.;
CC       Evidence={ECO:0000269|PubMed:20189825};
CC   -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
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DR   EMBL; M19169; AAA36115.1; -; Genomic_DNA.
DR   EMBL; J03870; AAA60299.1; -; mRNA.
DR   EMBL; AL591074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC021225; AAH21225.1; -; mRNA.
DR   CCDS; CCDS13160.1; -.
DR   PIR; A28110; UDHUP2.
DR   RefSeq; NP_001889.2; NM_001898.2.
DR   UniGene; Hs.123114; -.
DR   ProteinModelPortal; P01037; -.
DR   SMR; P01037; -.
DR   BioGrid; 107851; 38.
DR   IntAct; P01037; 4.
DR   STRING; 9606.ENSP00000305731; -.
DR   MEROPS; I25.010; -.
DR   BioMuta; CST1; -.
DR   DMDM; 311033460; -.
DR   EPD; P01037; -.
DR   jPOST; P01037; -.
DR   MaxQB; P01037; -.
DR   PaxDb; P01037; -.
DR   PeptideAtlas; P01037; -.
DR   PRIDE; P01037; -.
DR   ProteomicsDB; 51313; -.
DR   TopDownProteomics; P01037; -.
DR   Ensembl; ENST00000304749; ENSP00000305731; ENSG00000170373.
DR   Ensembl; ENST00000398402; ENSP00000381439; ENSG00000170373.
DR   GeneID; 1469; -.
DR   KEGG; hsa:1469; -.
DR   UCSC; uc002wtp.3; human.
DR   CTD; 1469; -.
DR   DisGeNET; 1469; -.
DR   EuPathDB; HostDB:ENSG00000170373.8; -.
DR   GeneCards; CST1; -.
DR   HGNC; HGNC:2473; CST1.
DR   HPA; CAB026769; -.
DR   HPA; HPA043706; -.
DR   HPA; HPA044763; -.
DR   MIM; 123855; gene.
DR   neXtProt; NX_P01037; -.
DR   OpenTargets; ENSG00000170373; -.
DR   PharmGKB; PA26972; -.
DR   eggNOG; ENOG410IZZH; Eukaryota.
DR   eggNOG; ENOG4112CFJ; LUCA.
DR   GeneTree; ENSGT00940000163410; -.
DR   HOGENOM; HOG000231754; -.
DR   HOVERGEN; HBG009556; -.
DR   InParanoid; P01037; -.
DR   KO; K13897; -.
DR   OMA; EVPWENR; -.
DR   OrthoDB; 1565344at2759; -.
DR   PhylomeDB; P01037; -.
DR   ChiTaRS; CST1; human.
DR   GeneWiki; CST1; -.
DR   GenomeRNAi; 1469; -.
DR   PRO; PR:P01037; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   Bgee; ENSG00000170373; Expressed in 72 organ(s), highest expression level in saliva-secreting gland.
DR   Genevisible; P01037; HS.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; TAS:ProtInc.
DR   GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; IDA:UniProtKB.
DR   CDD; cd00042; CY; 1.
DR   InterPro; IPR027214; Cystatin.
DR   InterPro; IPR000010; Cystatin_dom.
DR   InterPro; IPR018073; Prot_inh_cystat_CS.
DR   PANTHER; PTHR11413; PTHR11413; 1.
DR   Pfam; PF00031; Cystatin; 1.
DR   SMART; SM00043; CY; 1.
DR   PROSITE; PS00287; CYSTATIN; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Direct protein sequencing; Disulfide bond;
KW   Polymorphism; Protease inhibitor; Reference proteome; Secreted;
KW   Signal; Thiol protease inhibitor.
FT   SIGNAL        1     20       {ECO:0000269|PubMed:11788998,
FT                                ECO:0000269|PubMed:15340161,
FT                                ECO:0000269|PubMed:1778989}.
FT   CHAIN        21    141       Cystatin-SN.
FT                                /FTId=PRO_0000006649.
FT   MOTIF        76     80       Secondary area of contact.
FT   SITE         32     32       Reactive site.
FT   DISULFID     94    104       {ECO:0000269|PubMed:20189825}.
FT   DISULFID    118    138       {ECO:0000269|PubMed:20189825}.
FT   VARIANT       4      4       Y -> H (in dbSNP:rs6076122).
FT                                {ECO:0000269|PubMed:2837486,
FT                                ECO:0000269|PubMed:3446578}.
FT                                /FTId=VAR_028932.
FT   VARIANT      31     31       P -> L (in dbSNP:rs2070856).
FT                                /FTId=VAR_028933.
FT   VARIANT     129    129       N -> D (in dbSNP:rs3188319).
FT                                /FTId=VAR_028934.
FT   VARIANT     131    131       R -> M (in dbSNP:rs3188320).
FT                                /FTId=VAR_028935.
FT   VARIANT     135    135       K -> N (in dbSNP:rs3188322).
FT                                /FTId=VAR_028936.
SQ   SEQUENCE   141 AA;  16388 MW;  9F9934704D6C077D CRC64;
     MAQYLSTLLL LLATLAVALA WSPKEEDRII PGGIYNADLN DEWVQRALHF AISEYNKATK
     DDYYRRPLRV LRARQQTVGG VNYFFDVEVG RTICTKSQPN LDTCAFHEQP ELQKKQLCSF
     EIYEVPWENR RSLVKSRCQE S
//