CYTT_HUMAN
ID CYTT_HUMAN Reviewed; 141 AA.
AC P09228; Q9UCQ7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Cystatin-SA;
DE AltName: Full=Cystatin-2;
DE AltName: Full=Cystatin-S5;
DE Flags: Precursor;
GN Name=CST2;
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].
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 [GENOMIC DNA].
RA Dickinson D.P., Hewett-Emmett D., Thiesse M.;
RT "Acquisition of complex patterns of differential expression in epithelial
RT cell populations during the evolution of type 2 cystatin genes.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
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=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 [5]
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 [6]
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 [7]
RP PROTEIN SEQUENCE OF 25-141.
RX PubMed=3436950; DOI=10.1093/oxfordjournals.jbchem.a122107;
RA Isemura S., Saitoh E., Sanada K.;
RT "Characterization and amino acid sequence of a new acidic cysteine
RT proteinase inhibitor (cystatin SA) structurally closely related to cystatin
RT S, from human whole saliva.";
RL J. Biochem. 102:693-704(1987).
RN [8]
RP PRELIMINARY PROTEIN SEQUENCE OF 25-141.
RA Isemura S., Saitoh E., Sanada K., Isemura M., Ito S.;
RT "Characterization and amino acid sequence of a new acidic cysteine
RT proteinase inhibitor (cystatin SA) structurally closely related to cystatin
RT S, from human whole saliva.";
RL (In) Turk V. (eds.);
RL Cysteine proteinases and their inhibitors, pp.497-505, Walter de Gruyter,
RL Berlin and New York (1986).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-141.
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 [10]
RP TISSUE SPECIFICITY.
RX PubMed=11879580; DOI=10.1089/10445490252810311;
RA Dickinson D.P., Thiesse M., Hicks M.J.;
RT "Expression of type 2 cystatin genes CST1-CST5 in adult human tissues and
RT the developing submandibular gland.";
RL DNA Cell Biol. 21:47-65(2002).
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).
RN [12]
RP 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).
CC -!- FUNCTION: Thiol protease inhibitor.
CC -!- INTERACTION:
CC P09228; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-8832659, EBI-10173507;
CC P09228; Q92624: APPBP2; NbExp=3; IntAct=EBI-8832659, EBI-743771;
CC P09228; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-8832659, EBI-3867333;
CC P09228; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-8832659, EBI-11959885;
CC P09228; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-8832659, EBI-945833;
CC P09228; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-8832659, EBI-22310682;
CC P09228; P07237: P4HB; NbExp=3; IntAct=EBI-8832659, EBI-395883;
CC P09228; P25788: PSMA3; NbExp=3; IntAct=EBI-8832659, EBI-348380;
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
CC submandibular gland and parotid gland. {ECO:0000269|PubMed:11879580,
CC ECO:0000269|PubMed:20189825}.
CC -!- MASS SPECTROMETRY: Mass=14336.9856; Mass_error=0.0158;
CC Method=Electrospray; Evidence={ECO:0000269|PubMed:20189825};
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M19673; AAA36116.1; -; Genomic_DNA.
DR EMBL; M19671; AAA36116.1; JOINED; Genomic_DNA.
DR EMBL; M19672; AAA36116.1; JOINED; Genomic_DNA.
DR EMBL; AF319564; AAK11570.1; -; Genomic_DNA.
DR EMBL; AL591074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062679; AAH62679.1; -; mRNA.
DR CCDS; CCDS13161.1; -.
DR PIR; B29632; B29632.
DR RefSeq; NP_001313.1; NM_001322.2.
DR AlphaFoldDB; P09228; -.
DR SMR; P09228; -.
DR BioGRID; 107852; 56.
DR IntAct; P09228; 23.
DR STRING; 9606.ENSP00000307540; -.
DR MEROPS; I25.004; -.
DR MEROPS; I25.009; -.
DR BioMuta; CST2; -.
DR DMDM; 118192; -.
DR jPOST; P09228; -.
DR MassIVE; P09228; -.
DR PaxDb; P09228; -.
DR PeptideAtlas; P09228; -.
DR PRIDE; P09228; -.
DR ProteomicsDB; 52208; -.
DR Antibodypedia; 58258; 330 antibodies from 28 providers.
DR DNASU; 1470; -.
DR Ensembl; ENST00000304725.3; ENSP00000307540.2; ENSG00000170369.4.
DR GeneID; 1470; -.
DR KEGG; hsa:1470; -.
DR MANE-Select; ENST00000304725.3; ENSP00000307540.2; NM_001322.3; NP_001313.1.
DR UCSC; uc002wtq.2; human.
DR CTD; 1470; -.
DR DisGeNET; 1470; -.
DR GeneCards; CST2; -.
DR HGNC; HGNC:2474; CST2.
DR HPA; ENSG00000170369; Tissue enriched (salivary).
DR MIM; 123856; gene.
DR neXtProt; NX_P09228; -.
DR OpenTargets; ENSG00000170369; -.
DR PharmGKB; PA26975; -.
DR VEuPathDB; HostDB:ENSG00000170369; -.
DR eggNOG; ENOG502SC50; Eukaryota.
DR GeneTree; ENSGT00940000163410; -.
DR HOGENOM; CLU_118168_0_1_1; -.
DR InParanoid; P09228; -.
DR OMA; EAPADNC; -.
DR OrthoDB; 1565344at2759; -.
DR PhylomeDB; P09228; -.
DR PathwayCommons; P09228; -.
DR SignaLink; P09228; -.
DR BioGRID-ORCS; 1470; 14 hits in 1054 CRISPR screens.
DR GeneWiki; CST2; -.
DR GenomeRNAi; 1470; -.
DR Pharos; P09228; Tbio.
DR PRO; PR:P09228; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P09228; protein.
DR Bgee; ENSG00000170369; Expressed in parotid gland and 92 other tissues.
DR Genevisible; P09228; 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:15340161,
FT ECO:0000269|PubMed:1778989"
FT CHAIN 21..141
FT /note="Cystatin-SA"
FT /id="PRO_0000006652"
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"
SQ SEQUENCE 141 AA; 16445 MW; EB54915B1B977AA2 CRC64;
MAWPLCTLLL LLATQAVALA WSPQEEDRII EGGIYDADLN DERVQRALHF VISEYNKATE
DEYYRRLLRV LRAREQIVGG VNYFFDIEVG RTICTKSQPN LDTCAFHEQP ELQKKQLCSF
QIYEVPWEDR MSLVNSRCQE A
