CYTD_HUMAN
ID CYTD_HUMAN Reviewed; 142 AA.
AC P28325; Q5JRF5; Q9UCA0;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Cystatin-D;
DE AltName: Full=Cystatin-5;
DE Flags: Precursor;
GN Name=CST5;
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].
RC TISSUE=Leukocyte;
RX PubMed=1939105; DOI=10.1016/s0021-9258(18)54958-9;
RA Freije J.P., Abrahamson M., Olafssonn I., Velasco G., Grubb A.,
RA Lopez-Otin C.;
RT "Structure and expression of the gene encoding cystatin D, a novel human
RT cysteine proteinase inhibitor.";
RL J. Biol. Chem. 266:20538-20543(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Parotid gland;
RX PubMed=8340398; DOI=10.1016/s0021-9258(18)82317-1;
RA Freije J.P., Balbin M., Abrahamson M., Velasco G., Dalboge H., Grubb A.,
RA Lopez-Otin C.;
RT "Human cystatin D. cDNA cloning, characterization of the Escherichia coli
RT expressed inhibitor, and identification of the native protein in saliva.";
RL J. Biol. Chem. 268:15737-15744(1993).
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].
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 21-38, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RX PubMed=8083219; DOI=10.1016/s0021-9258(17)31633-2;
RA Balbin M., Hall A., Grubb A., Mason R.W., Lopez-Otin C., Abrahamson M.;
RT "Structural and functional characterization of two allelic variants of
RT human cystatin D sharing a characteristic inhibition spectrum against
RT mammalian cysteine proteinases.";
RL J. Biol. Chem. 269:23156-23162(1994).
RN [6]
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 21-142, AND DISULFIDE BONDS.
RX PubMed=15728581; DOI=10.1074/jbc.m411914200;
RA Alvarez-Fernandez M., Liang Y.H., Abrahamson M., Su X.D.;
RT "Crystal structure of human cystatin D, a cysteine peptidase inhibitor with
RT restricted inhibition profile.";
RL J. Biol. Chem. 280:18221-18228(2005).
RN [8]
RP VARIANT ARG-46.
RX PubMed=8444475; DOI=10.1007/bf00202491;
RA Balbin M., Freije J.P., Abrahamson M., Velasco G., Lopez-Otin C.;
RT "A sequence variation in the human cystatin D gene resulting in an amino
RT acid (Cys/Arg) polymorphism at the protein level.";
RL Hum. Genet. 90:668-669(1993).
CC -!- FUNCTION: Cysteine proteinase inhibitor that possibly plays a
CC protective role against proteinases present in the oral cavity. The
CC order of preference for inhibition is cathepsin S > cathepsin H >
CC cathepsin L > cathepsin B. {ECO:0000269|PubMed:8083219}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable. {ECO:0000269|PubMed:8083219};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8083219}.
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 parotid
CC gland but not in seminal vesicle, prostate, epididymis, testis, ovary,
CC placenta, thyroid, gastric corpus, small intestine, liver, or gall
CC bladder tissue. {ECO:0000269|PubMed:20189825}.
CC -!- MASS SPECTROMETRY: Mass=13154.4675; Mass_error=0.0101;
CC Method=Electrospray; Note=Variant Arg-46.;
CC Evidence={ECO:0000269|PubMed:20189825};
CC -!- MASS SPECTROMETRY: Mass=13596.7015; Mass_error=0.0049;
CC Method=Electrospray; Note=Variant Arg-46.;
CC Evidence={ECO:0000269|PubMed:20189825};
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
CC -!- CAUTION: The truncated forms found may result from N-terminal
CC proteolysis. {ECO:0000305|PubMed:20189825}.
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DR EMBL; X59964; CAA42590.1; -; Genomic_DNA.
DR EMBL; X70377; CAA49838.1; -; mRNA.
DR EMBL; AL591074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062678; AAH62678.1; -; mRNA.
DR EMBL; BC069514; AAH69514.1; -; mRNA.
DR CCDS; CCDS13162.1; -.
DR PIR; A47142; A47142.
DR RefSeq; NP_001891.2; NM_001900.4.
DR PDB; 1RN7; X-ray; 2.50 A; A=21-142.
DR PDB; 1ROA; X-ray; 1.80 A; A=21-142.
DR PDBsum; 1RN7; -.
DR PDBsum; 1ROA; -.
DR AlphaFoldDB; P28325; -.
DR SMR; P28325; -.
DR BioGRID; 107855; 39.
DR IntAct; P28325; 7.
DR STRING; 9606.ENSP00000307132; -.
DR MEROPS; I25.005; -.
DR BioMuta; CST5; -.
DR jPOST; P28325; -.
DR MassIVE; P28325; -.
DR PaxDb; P28325; -.
DR PeptideAtlas; P28325; -.
DR PRIDE; P28325; -.
DR ProteomicsDB; 54464; -.
DR Antibodypedia; 24931; 142 antibodies from 21 providers.
DR DNASU; 1473; -.
DR Ensembl; ENST00000304710.5; ENSP00000307132.4; ENSG00000170367.5.
DR GeneID; 1473; -.
DR KEGG; hsa:1473; -.
DR MANE-Select; ENST00000304710.5; ENSP00000307132.4; NM_001900.5; NP_001891.2.
DR UCSC; uc002wtr.2; human.
DR CTD; 1473; -.
DR DisGeNET; 1473; -.
DR GeneCards; CST5; -.
DR HGNC; HGNC:2477; CST5.
DR HPA; ENSG00000170367; Tissue enriched (salivary).
DR MIM; 123858; gene.
DR neXtProt; NX_P28325; -.
DR OpenTargets; ENSG00000170367; -.
DR PharmGKB; PA26978; -.
DR VEuPathDB; HostDB:ENSG00000170367; -.
DR eggNOG; ENOG502SC50; Eukaryota.
DR GeneTree; ENSGT00940000164560; -.
DR HOGENOM; CLU_118168_0_1_1; -.
DR InParanoid; P28325; -.
DR OMA; FTIREYN; -.
DR OrthoDB; 1565344at2759; -.
DR PhylomeDB; P28325; -.
DR PathwayCommons; P28325; -.
DR SignaLink; P28325; -.
DR BioGRID-ORCS; 1473; 9 hits in 1067 CRISPR screens.
DR ChiTaRS; CST5; human.
DR EvolutionaryTrace; P28325; -.
DR GeneWiki; CST5; -.
DR GenomeRNAi; 1473; -.
DR Pharos; P28325; Tbio.
DR PRO; PR:P28325; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P28325; protein.
DR Bgee; ENSG00000170367; Expressed in parotid gland and 47 other tissues.
DR Genevisible; P28325; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; 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 3D-structure; Direct protein sequencing; Disulfide bond;
KW Protease inhibitor; Reference proteome; Secreted; Signal;
KW Thiol protease inhibitor.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:8083219"
FT CHAIN 21..142
FT /note="Cystatin-D"
FT /id="PRO_0000006645"
FT MOTIF 70..74
FT /note="Secondary area of contact"
FT SITE 32
FT /note="Reactive site"
FT /evidence="ECO:0000250"
FT DISULFID 95..105
FT DISULFID 119..139
FT VARIANT 46
FT /note="C -> R (in 45% of the population; dbSNP:rs1799841)"
FT /evidence="ECO:0000269|PubMed:8444475"
FT /id="VAR_002208"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:1ROA"
FT HELIX 42..57
FT /evidence="ECO:0007829|PDB:1ROA"
FT STRAND 63..78
FT /evidence="ECO:0007829|PDB:1ROA"
FT STRAND 81..96
FT /evidence="ECO:0007829|PDB:1ROA"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:1RN7"
FT STRAND 117..126
FT /evidence="ECO:0007829|PDB:1ROA"
FT TURN 127..130
FT /evidence="ECO:0007829|PDB:1ROA"
FT STRAND 131..141
FT /evidence="ECO:0007829|PDB:1ROA"
SQ SEQUENCE 142 AA; 16080 MW; CEFA89BA87A0DA68 CRC64;
MMWPMHTPLL LLTALMVAVA GSASAQSRTL AGGIHATDLN DKSVQCALDF AISEYNKVIN
KDEYYSRPLQ VMAAYQQIVG GVNYYFNVKF GRTTCTKSQP NLDNCPFNDQ PKLKEEEFCS
FQINEVPWED KISILNYKCR KV
