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P01036 (CYTS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cystatin-S
Alternative name(s):
Cystatin-4
Cystatin-SA-III
Salivary acidic protein 1
Gene names
Name:CST4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length141 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Secreted Ref.13.

Tissue specificity

Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in saliva, tears, urine and seminal fluid. Ref.13

Post-translational modification

Phosphorylated at both its N- and C-terminal regions. Ref.7 Ref.8 Ref.9 Ref.12 Ref.13

Sequence similarities

Belongs to the cystatin family.

Mass spectrometry

Molecular mass is 14175.8569±0.0564 Da from positions 21 - 141. Determined by ESI. Ref.13

Molecular mass is 14255.8567±0.0899 Da from positions 21 - 141. Determined by ESI. Monophosphorylated at Ser-23, also called form S1. Ref.13

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. Ref.13

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Ref.6 Ref.7 Ref.8 Ref.9
Chain21 – 141121Cystatin-S
PRO_0000006650

Regions

Motif76 – 805Secondary area of contact

Sites

Site321Reactive site

Amino acid modifications

Modified residue211Phosphoserine Ref.8 Ref.13
Modified residue231Phosphoserine Ref.7 Ref.8 Ref.9 Ref.13
Disulfide bond94 ↔ 104 By similarity
Disulfide bond118 ↔ 138 By similarity

Natural variations

Natural variant361D → N.
Corresponds to variant rs3210291 [ dbSNP | Ensembl ].
VAR_048852
Natural variant771T → N in a breast cancer sample; somatic mutation. Ref.14
VAR_036549

Experimental info

Sequence conflict1351N → D AA sequence Ref.10

Sequences

Sequence LengthMass (Da)Tools
P01036 [UniParc].

Last modified July 1, 1993. Version 3.
Checksum: 65B1FEB8F074DEA6

FASTA14116,214
        10         20         30         40         50         60 
MARPLCTLLL LMATLAGALA SSSKEENRII PGGIYDADLN DEWVQRALHF AISEYNKATE 

        70         80         90        100        110        120 
DEYYRRPLQV LRAREQTFGG VNYFFDVEVG RTICTKSQPN LDTCAFHEQP ELQKKQLCSF 

       130        140 
EIYEVPWEDR MSLVNSRCQE A 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-77.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRUDHUP1. S17667.
RefSeqNP_001890.1. NM_001899.2.
UniGeneHs.654549.

3D structure databases

ProteinModelPortalP01036.
SMRP01036. Positions 32-140.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107854. 1 interaction.
STRING9606.ENSP00000217423.

Protein family/group databases

MEROPSI25.008.

PTM databases

PhosphoSiteP01036.

Polymorphism databases

DMDM399336.

Proteomic databases

PaxDbP01036.
PeptideAtlasP01036.
PRIDEP01036.

Protocols and materials databases

DNASU1472.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000217423; ENSP00000217423; ENSG00000101441.
GeneID1472.
KEGGhsa:1472.
UCSCuc002wto.1. human.

Organism-specific databases

CTD1472.
GeneCardsGC20M023666.
HGNCHGNC:2476. CST4.
HPAHPA043706.
HPA044763.
MIM123857. gene.
neXtProtNX_P01036.
PharmGKBPA26977.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44865.
HOGENOMHOG000231754.
HOVERGENHBG009556.
InParanoidP01036.
KOK13900.
OMADIARTEC.
OrthoDBEOG7M98J9.
PhylomeDBP01036.

Gene expression databases

BgeeP01036.
CleanExHS_CST4.
GenevestigatorP01036.

Family and domain databases

InterProIPR027214. Cystatin.
IPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERPTHR11413. PTHR11413. 1 hit.
PfamPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTSM00043. CY. 1 hit.
[Graphical view]
PROSITEPS00287. CYSTATIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCST4.
GenomeRNAi1472.
NextBio6043.
PROP01036.
SOURCESearch...

Entry information

Entry nameCYTS_HUMAN
AccessionPrimary (citable) accession number: P01036
Secondary accession number(s): Q9UBI5, Q9UCS9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1993
Last modified: April 16, 2014
This is version 143 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM