CYTN_HUMAN
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 03-AUG-2022, entry version 202.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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; DOI=10.1016/s0021-9258(19)76552-1;
RA Al-Hashimi I., Dickinson D.P., Levine M.J.;
RT "Purification, molecular cloning, and sequencing of salivary cystatin SA-
RT 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 project:
RT 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-smokers and
RT smokers using two-dimensional gel electrophoresis and peptide mass
RT 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 saliva,
RT 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 verified
RT 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 followed
RT 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 using
RT top-down Fourier-transform ion cyclotron resonance mass spectrometry.";
RL J. Am. Soc. Mass Spectrom. 21:908-917(2010).
CC -!- FUNCTION: Human saliva appears to contain several cysteine proteinase
CC inhibitors that are immunologically related to cystatin S but that
CC differ in their specificity due to amino acid sequence differences.
CC Cystatin SN, with a pI of 7.5, is a much better inhibitor of papain and
CC dipeptidyl peptidase I than is cystatin S, although both inhibit ficin
CC equally well.
CC -!- INTERACTION:
CC P01037; Q12797-6: ASPH; NbExp=3; IntAct=EBI-1056240, EBI-12092171;
CC P01037; P67870: CSNK2B; NbExp=3; IntAct=EBI-1056240, EBI-348169;
CC P01037; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-1056240, EBI-725665;
CC P01037; O43765: SGTA; NbExp=3; IntAct=EBI-1056240, EBI-347996;
CC P01037; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-1056240, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20189825}.
CC -!- TISSUE SPECIFICITY: Expressed in submandibular and sublingual saliva
CC but not in parotid saliva (at protein level). Expressed in saliva,
CC tears, urine and seminal fluid. {ECO:0000269|PubMed:20189825}.
CC -!- MASS SPECTROMETRY: Mass=14303.1553; Mass_error=0.0675;
CC Method=Electrospray; Evidence={ECO:0000269|PubMed:20189825};
CC -!- MASS SPECTROMETRY: Mass=14319.171; Mass_error=0.0523;
CC Method=Electrospray; 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 AlphaFoldDB; P01037; -.
DR SMR; P01037; -.
DR BioGRID; 107851; 90.
DR IntAct; P01037; 41.
DR MINT; P01037; -.
DR STRING; 9606.ENSP00000305731; -.
DR MEROPS; I25.010; -.
DR BioMuta; CST1; -.
DR DMDM; 311033460; -.
DR EPD; P01037; -.
DR jPOST; P01037; -.
DR MassIVE; P01037; -.
DR MaxQB; P01037; -.
DR PaxDb; P01037; -.
DR PeptideAtlas; P01037; -.
DR PRIDE; P01037; -.
DR ProteomicsDB; 51313; -.
DR TopDownProteomics; P01037; -.
DR Antibodypedia; 24921; 252 antibodies from 30 providers.
DR DNASU; 1469; -.
DR Ensembl; ENST00000304749.7; ENSP00000305731.2; ENSG00000170373.9.
DR Ensembl; ENST00000398402.1; ENSP00000381439.1; ENSG00000170373.9.
DR GeneID; 1469; -.
DR KEGG; hsa:1469; -.
DR MANE-Select; ENST00000304749.7; ENSP00000305731.2; NM_001898.3; NP_001889.2.
DR UCSC; uc002wtp.3; human.
DR CTD; 1469; -.
DR DisGeNET; 1469; -.
DR GeneCards; CST1; -.
DR HGNC; HGNC:2473; CST1.
DR HPA; ENSG00000170373; Tissue enriched (salivary).
DR MIM; 123855; gene.
DR neXtProt; NX_P01037; -.
DR OpenTargets; ENSG00000170373; -.
DR PharmGKB; PA26972; -.
DR VEuPathDB; HostDB:ENSG00000170373; -.
DR eggNOG; ENOG502SC50; Eukaryota.
DR GeneTree; ENSGT00940000163410; -.
DR HOGENOM; CLU_118168_0_1_1; -.
DR InParanoid; P01037; -.
DR OMA; LAFGFCQ; -.
DR OrthoDB; 1565344at2759; -.
DR PhylomeDB; P01037; -.
DR PathwayCommons; P01037; -.
DR SignaLink; P01037; -.
DR BioGRID-ORCS; 1469; 12 hits in 1064 CRISPR screens.
DR ChiTaRS; CST1; human.
DR GeneWiki; CST1; -.
DR GenomeRNAi; 1469; -.
DR Pharos; P01037; Tbio.
DR PRO; PR:P01037; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P01037; protein.
DR Bgee; ENSG00000170373; Expressed in gall bladder and 82 other tissues.
DR Genevisible; P01037; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; IDA:UniProtKB.
DR GO; GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IBA:GO_Central.
DR CDD; cd00042; CY; 1.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR Pfam; PF00031; Cystatin; 1.
DR SMART; SM00043; CY; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Protease inhibitor;
KW Reference proteome; Secreted; Signal; Thiol protease inhibitor.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:11788998,
FT ECO:0000269|PubMed:15340161, ECO:0000269|PubMed:1778989"
FT CHAIN 21..141
FT /note="Cystatin-SN"
FT /id="PRO_0000006649"
FT MOTIF 76..80
FT /note="Secondary area of contact"
FT SITE 32
FT /note="Reactive site"
FT DISULFID 94..104
FT /evidence="ECO:0000269|PubMed:20189825"
FT DISULFID 118..138
FT /evidence="ECO:0000269|PubMed:20189825"
FT VARIANT 4
FT /note="Y -> H (in dbSNP:rs6076122)"
FT /evidence="ECO:0000269|PubMed:2837486,
FT ECO:0000269|PubMed:3446578"
FT /id="VAR_028932"
FT VARIANT 31
FT /note="P -> L (in dbSNP:rs2070856)"
FT /id="VAR_028933"
FT VARIANT 129
FT /note="N -> D (in dbSNP:rs3188319)"
FT /id="VAR_028934"
FT VARIANT 131
FT /note="R -> M (in dbSNP:rs3188320)"
FT /id="VAR_028935"
FT VARIANT 135
FT /note="K -> N (in dbSNP:rs3188322)"
FT /id="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
