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Protein

Cystatin-S

Gene

CST4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This protein strongly inhibits papain and ficin, partially inhibits stem bromelain and bovine cathepsin C, but does not inhibit porcine cathepsin B or clostripain. Papain is inhibited non-competitively.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei32 – 321Reactive site

GO - Molecular functioni

  • cysteine-type endopeptidase inhibitor activity Source: UniProtKB

GO - Biological processi

  • detection of chemical stimulus involved in sensory perception of bitter taste Source: UniProtKB
  • negative regulation of endopeptidase activity Source: GOC
  • negative regulation of proteolysis Source: UniProtKB
  • retina homeostasis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Thiol protease inhibitor

Protein family/group databases

MEROPSiI25.008.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystatin-S
Alternative name(s):
Cystatin-4
Cystatin-SA-III
Salivary acidic protein 1
Gene namesi
Name:CST4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:2476. CST4.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26977.

Polymorphism and mutation databases

BioMutaiCST4.
DMDMi399336.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20204 PublicationsAdd
BLAST
Chaini21 – 141121Cystatin-SPRO_0000006650Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei21 – 211Phosphoserine2 Publications
Modified residuei23 – 231Phosphoserine4 Publications
Disulfide bondi94 ↔ 104By similarity
Disulfide bondi118 ↔ 138By similarity

Post-translational modificationi

Phosphorylated at both its N- and C-terminal regions.5 Publications

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiP01036.
PaxDbiP01036.
PeptideAtlasiP01036.
PRIDEiP01036.

PTM databases

PhosphoSiteiP01036.

Expressioni

Tissue specificityi

Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in saliva, tears, urine and seminal fluid.1 Publication

Gene expression databases

BgeeiP01036.
CleanExiHS_CST4.
GenevestigatoriP01036.

Organism-specific databases

HPAiHPA043706.
HPA044763.

Interactioni

Protein-protein interaction databases

BioGridi107854. 22 interactions.
STRINGi9606.ENSP00000217423.

Structurei

3D structure databases

ProteinModelPortaliP01036.
SMRiP01036. Positions 32-140.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi76 – 805Secondary area of contact

Sequence similaritiesi

Belongs to the cystatin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG44865.
GeneTreeiENSGT00570000079039.
HOGENOMiHOG000231754.
HOVERGENiHBG009556.
InParanoidiP01036.
KOiK13900.
OMAiDIARTEC.
OrthoDBiEOG7M98J9.
PhylomeDBiP01036.

Family and domain databases

InterProiIPR027214. Cystatin.
IPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERiPTHR11413. PTHR11413. 1 hit.
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01036-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARPLCTLLL LMATLAGALA SSSKEENRII PGGIYDADLN DEWVQRALHF
60 70 80 90 100
AISEYNKATE DEYYRRPLQV LRAREQTFGG VNYFFDVEVG RTICTKSQPN
110 120 130 140
LDTCAFHEQP ELQKKQLCSF EIYEVPWEDR MSLVNSRCQE A
Length:141
Mass (Da):16,214
Last modified:July 1, 1993 - v3
Checksum:i65B1FEB8F074DEA6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti135 – 1351N → D AA sequence (PubMed:6501254).Curated

Mass spectrometryi

Molecular mass is 14175.8569±0.0564 Da from positions 21 - 141. Determined by ESI. 1 Publication
Molecular mass is 14255.8567±0.0899 Da from positions 21 - 141. Determined by ESI. Monophosphorylated at Ser-23, also called form S1.1 Publication
Molecular mass is 14335.811±0.0775 Da from positions 21 - 141. Determined by ESI. Diphosphorylated at Ser-21 and Ser-23, also called form S2.1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361D → N.
Corresponds to variant rs3210291 [ dbSNP | Ensembl ].
VAR_048852
Natural varianti77 – 771T → N in a breast cancer sample; somatic mutation. 1 Publication
VAR_036549

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54667 mRNA. Translation: CAA38478.1.
S51222, S51214, S51219 Genomic DNA. Translation: AAB24493.1.
AF319565 Genomic DNA. Translation: AAK11571.1.
AL359433 Genomic DNA. Translation: CAC07196.1.
BC065714 mRNA. Translation: AAH65714.1.
BC074952 mRNA. Translation: AAH74952.1.
BC074953 mRNA. Translation: AAH74953.1.
CCDSiCCDS13159.1.
PIRiS17667. UDHUP1.
RefSeqiNP_001890.1. NM_001899.2.
UniGeneiHs.654549.

Genome annotation databases

EnsembliENST00000217423; ENSP00000217423; ENSG00000101441.
GeneIDi1472.
KEGGihsa:1472.
UCSCiuc002wto.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54667 mRNA. Translation: CAA38478.1.
S51222, S51214, S51219 Genomic DNA. Translation: AAB24493.1.
AF319565 Genomic DNA. Translation: AAK11571.1.
AL359433 Genomic DNA. Translation: CAC07196.1.
BC065714 mRNA. Translation: AAH65714.1.
BC074952 mRNA. Translation: AAH74952.1.
BC074953 mRNA. Translation: AAH74953.1.
CCDSiCCDS13159.1.
PIRiS17667. UDHUP1.
RefSeqiNP_001890.1. NM_001899.2.
UniGeneiHs.654549.

3D structure databases

ProteinModelPortaliP01036.
SMRiP01036. Positions 32-140.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107854. 22 interactions.
STRINGi9606.ENSP00000217423.

Protein family/group databases

MEROPSiI25.008.

PTM databases

PhosphoSiteiP01036.

Polymorphism and mutation databases

BioMutaiCST4.
DMDMi399336.

Proteomic databases

MaxQBiP01036.
PaxDbiP01036.
PeptideAtlasiP01036.
PRIDEiP01036.

Protocols and materials databases

DNASUi1472.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000217423; ENSP00000217423; ENSG00000101441.
GeneIDi1472.
KEGGihsa:1472.
UCSCiuc002wto.1. human.

Organism-specific databases

CTDi1472.
GeneCardsiGC20M023666.
HGNCiHGNC:2476. CST4.
HPAiHPA043706.
HPA044763.
MIMi123857. gene.
neXtProtiNX_P01036.
PharmGKBiPA26977.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG44865.
GeneTreeiENSGT00570000079039.
HOGENOMiHOG000231754.
HOVERGENiHBG009556.
InParanoidiP01036.
KOiK13900.
OMAiDIARTEC.
OrthoDBiEOG7M98J9.
PhylomeDBiP01036.

Miscellaneous databases

ChiTaRSiCST4. human.
GeneWikiiCST4.
GenomeRNAii1472.
NextBioi6043.
PROiP01036.
SOURCEiSearch...

Gene expression databases

BgeeiP01036.
CleanExiHS_CST4.
GenevestigatoriP01036.

Family and domain databases

InterProiIPR027214. Cystatin.
IPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERiPTHR11413. PTHR11413. 1 hit.
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human salivary cystatin S. Cloning, sequence analysis, hybridization in situ and immunocytochemistry."
    Bobek L.A., Aguirre A., Levine M.J.
    Biochem. J. 278:627-635(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Submandibular gland.
  2. "Characterization of two members (CST4 and CST5) of the cystatin gene family and molecular evolution of cystatin genes."
    Saitoh E., Isemura S., Sanada K., Ohnishi K.
    Agents Actions 38:340-348(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Acquisition of complex patterns of differential expression in epithelial cell populations during the evolution of type 2 cystatin genes."
    Dickinson D.P., Hewett-Emmett D., Thiesse M.
    Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Thyroid.
  6. "Identification of a long form of cystatin from human saliva by rapid microbore HPLC mapping."
    Hawke D.H., Yuan P.M., Wilson K.J., Hunkapiller M.W.
    Biochem. Biophys. Res. Commun. 145:1248-1253(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-51.
  7. "Large-scale purification and characterization of the major phosphoproteins and mucins of human submandibular-sublingual saliva."
    Ramasubbu N., Reddy M.S., Bergey E.J., Haraszthy G.G., Soni S.-D., Levine M.J.
    Biochem. J. 280:341-352(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-55, PHOSPHORYLATION AT SER-23.
    Tissue: Saliva.
  8. "Identification of full-sized forms of salivary (S-type) cystatins (cystatin SN, cystatin SA, cystatin S, and two phosphorylated forms of cystatin S) in human whole saliva and determination of phosphorylation sites of cystatin S."
    Isemura S., Saitoh E., Sanada K., Minakata K.
    J. Biochem. 110:648-654(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-36, PHOSPHORYLATION AT SER-21 AND SER-23.
    Tissue: Saliva.
  9. "The effects of human salivary cystatins and statherin on hydroxyapatite crystallization."
    Johnsson M., Richardson C.F., Bergey E.J., Levine M.J., Nancollas G.H.
    Arch. Oral Biol. 36:631-636(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-36, PHOSPHORYLATION AT SER-23.
    Tissue: Saliva.
  10. "Isolation and amino acid sequence of SAP-1, an acidic protein of human whole saliva, and sequence homology with human gamma-trace."
    Isemura S., Saitoh E., Sanada K.
    J. Biochem. 96:489-498(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 29-141.
  11. "Cystatin S: a cysteine proteinase inhibitor of human saliva."
    Isemura S., Saitoh E., Ito S., Isemura M., Sanada K.
    J. Biochem. 96:1311-1314(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITOR SPECIFICITY.
  12. "Salivary cystatin SA-III, a potential precursor of the acquired enamel pellicle, is phosphorylated at both its amino- and carboxyl-terminal regions."
    Lamkin M.S., Jensen J.L., Setayesh M.R., Troxler R.F., Oppenheim F.G.
    Arch. Biochem. Biophys. 288:664-670(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  13. "Confident assignment of intact mass tags to human salivary cystatins using top-down Fourier-transform ion cyclotron resonance mass spectrometry."
    Ryan C.M., Souda P., Halgand F., Wong D.T., Loo J.A., Faull K.F., Whitelegge J.P.
    J. Am. Soc. Mass Spectrom. 21:908-917(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-21 AND SER-23, DISULFIDE BONDS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
    Tissue: Saliva.
  14. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-77.

Entry informationi

Entry nameiCYTS_HUMAN
AccessioniPrimary (citable) accession number: P01036
Secondary accession number(s): Q9UBI5, Q9UCS9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1993
Last modified: May 27, 2015
This is version 153 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.