P01036 (CYTS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cystatin-S

Alternative name(s):
Cystatin-4
Cystatin-SA-III
Salivary acidic protein 1

Gene names

Name:

CST4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	141 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Protease inhibitor Thiol protease inhibitor
PTM	Disulfide bond Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Ref.6 Ref.7 Ref.8 Ref.9
	Chain	21 – 141	121	Cystatin-S		PRO_0000006650
Regions
	Motif	76 – 80	5	Secondary area of contact
Sites
	Site	32	1	Reactive site
Amino acid modifications
	Modified residue	21	1	Phosphoserine Ref.8 Ref.13
	Modified residue	23	1	Phosphoserine Ref.7 Ref.8 Ref.9 Ref.13
	Disulfide bond	94 ↔ 104		By similarity
	Disulfide bond	118 ↔ 138		By similarity
Natural variations
	Natural variant	36	1	D → N. Corresponds to variant rs3210291 [ dbSNP | Ensembl ].		VAR_048852
	Natural variant	77	1	T → N in a breast cancer sample; somatic mutation. Ref.14		VAR_036549
Experimental info
	Sequence conflict	135	1	N → D AA sequence Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P01036 [UniParc]. Last modified July 1, 1993. Version 3. Checksum: 65B1FEB8F074DEA6	FASTA	141	16,214
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00032294.
PIR	UDHUP1. S17667.
RefSeq	NP_001890.1. NM_001899.2.
UniGene	Hs.654549.
3D structure databases
ProteinModelPortal	P01036.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000217423.
Protein family/group databases
MEROPS	I25.008.
PTM databases
PhosphoSite	P01036.
Polymorphism databases
DMDM	399336.
Proteomic databases
PaxDb	P01036.
PeptideAtlas	P01036.
PRIDE	P01036.
Protocols and materials databases
DNASU	1472.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000217423; ENSP00000217423; ENSG00000101441.
GeneID	1472.
KEGG	hsa:1472.
UCSC	uc002wto.1. human.
Organism-specific databases
CTD	1472.
GeneCards	GC20M023666.
HGNC	HGNC:2476. CST4.
MIM	123857. gene.
neXtProt	NX_P01036.
PharmGKB	PA26977.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG44865.
HOGENOM	HOG000231754.
HOVERGEN	HBG009556.
InParanoid	P01036.
KO	K13900.
OMA	DIARTEC.
OrthoDB	EOG4PG62B.
PhylomeDB	P01036.
Gene expression databases
Bgee	P01036.
CleanEx	HS_CST4.
Genevestigator	P01036.
GermOnline	ENSG00000101441. Homo sapiens.
Family and domain databases
InterPro	IPR027214. Cystatin. IPR000010. Prot_inh_cystat. IPR018073. Prot_inh_cystat_CS. [Graphical view]
PANTHER	PTHR11413. PTHR11413. 1 hit.
Pfam	PF00031. Cystatin. 1 hit. [Graphical view]
SMART	SM00043. CY. 1 hit. [Graphical view]
PROSITE	PS00287. CYSTATIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1472.
NextBio	6043.
SOURCE	Search...

Entry information

Entry name

CYTS_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.