Cystatin

Proteinase inhibitor I25, cystatin
Crystal structure of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata from PDB entry 3L0R.
Identifiers
Symbol	Prot_inh_cystat
Pfam	PF00031
Pfam clan	CL0121
InterPro	IPR000010
SMART	SM00043
PROSITE	PDOC00259
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB PDB: 1a67​ PDB: 1a90​ PDB: 1cew​ PDB: 1cyu​ PDB: 1cyv​ PDB: 1dvc​ PDB: 1dvd​ PDB: 1eqk​ PDB: 1g96​ PDB: 1gd3​

The cystatins are a family of cysteine protease inhibitors which share a sequence homology and a common tertiary structure of an alpha helix lying on top of an anti-parallel beta sheet. The family is subdivided as described below.

Cystatins show similarity to fetuins, kininogens, histidine-rich glycoproteins and cystatin-related proteins. Cystatins mainly inhibit peptidase enzymes (another term for proteases) belonging to peptidase families C1 (papain family) and C13 (legumain family). They are known to mis-fold to form amyloid deposits and are implicated in several diseases.

Types

The cystatin family includes:

• The Type 1 cystatins, which are intracellular and are present in the cytosol of many cell types, but can also appear in body fluids at significant concentrations. They are single-chain polypeptides of about 100 residues, which have neither disulfide bonds nor carbohydrate side-chains. Type 1 cystatins are also known as Stefins (after the Stefan Institute where they were first discovered )
• The Type 2 cystatins, which are mainly extracellular secreted polypeptides are largely acidic, contain four conserved cysteine residues known to form two disulfide bonds, may be glycosylated and/or phosphorylated. They are synthesised with a 19- to 28-residue signal peptide. They are broadly distributed and found in most body fluids.
• The Type 3 cystatins, which are multidomain proteins. The mammalian representatives of this group are the kininogens. There are three different kininogens in mammals: H- (high-molecular-mass, InterPro: IPR002395) and L- (low-molecular-mass) kininogen, which are found in a number of species, and T-kininogen, which is found only in rats.
• Unclassified cystatins. These are cystatin-like proteins found in a range of organisms: plant phytocystatins, fetuin in mammals, insect cystatins, and a puff adder venom cystatin, which inhibits metalloproteases of the MEROPS peptidase family M12 (astacin/adamalysin). Also, a number of the cystatin-like proteins have been shown to be devoid of inhibitory activity.

Human cystatins

• CST1, CST2, CST3 (cystatin C, a marker of kidney function), CST4, CST5, CST6, CST7, CST8, CST9, CST11, CSTA (cystatin A), CSTB (cystatin B)

See also

• Affimer, a type of engineered protein that is based on the cystatin scaffold

Further reading

• Cystatin: a protein that flips out! QUite Interesting PDB Structure article at PDBe

• Lee C, Bongcam-Rudloff E, Sollner C, Jahnen-Dechent W, Claesson-Welsh L (2009). "Type 3 cystatins; fetuins, kininogen and histidine-rich glycoprotein". Front. Biosci. 14 (14): 2911–22. doi:10.2741/3422. PMID 19273244.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

• Cystatins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR000010