Proteinase inhibitor I25, cystatin
Crystal structure of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata from PDB entry 3L0R.[1]
Pfam clanCL0121
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary
PDBPDB: 1a67PDB: 1a90PDB: 1cewPDB: 1cyuPDB: 1cyvPDB: 1dvcPDB: 1dvdPDB: 1eqkPDB: 1g96PDB: 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.[2][3][4] 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.[citation needed]


The cystatin family includes:

Human cystatins

Plant cystatins

Plant cystatins have special characteristics which permit them to be classified in a special class called Phytocystatin. One is the presence of a N-terminal alpha-helix, present only in plant cystatins. Phytocystatins are involved in several process, including plant germination and defense. van Wyk et al. found some 19 different cystatins similar to oryzacystatin-I in the soybean along with related cysteine proteases.[6]

Membrane permeability

Chicken cystatin quickly passed the membrane of MCF-10A neo T cells and inhibited cathepsin B when it was acylated with fatty acyl residues of 6-18 carbon atoms.[7][relevant?]

See also


  1. ^ Salát J, Paesen GC, Rezácová P, Kotsyfakis M, Kovárová Z, Sanda M, Majtán J, Grunclová L, Horká H, Andersen JF, Brynda J, Horn M, Nunn MA, Kopácek P, Kopecký J, Mares M (July 2010). "Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata". The Biochemical Journal. 429 (1): 103–12. doi:10.1042/BJ20100280. PMC 3523712. PMID 20545626.; rendered with PyMOL
  2. ^ Rawlings ND, Barrett AJ (January 1990). "Evolution of proteins of the cystatin superfamily". Journal of Molecular Evolution. 30 (1): 60–71. Bibcode:1990JMolE..30...60R. doi:10.1007/BF02102453. PMID 2107324. S2CID 33504413.
  3. ^ Abrahamson M, Alvarez-Fernandez M, Nathanson CM (2003). "Cystatins". Biochemical Society Symposium. 70 (70): 179–99. doi:10.1042/bss0700179. PMID 14587292.
  4. ^ Turk V, Bode W (July 1991). "The cystatins: protein inhibitors of cysteine proteinases". FEBS Letters. 285 (2): 213–9. doi:10.1016/0014-5793(91)80804-C. PMID 1855589. S2CID 40444629.
  5. ^ Machleidt W, Borchart U, Fritz H, Brzin J, Ritonja A, Turk V (November 1983). "Protein inhibitors of cysteine proteinases. II. Primary structure of stefin, a cytosolic protein inhibitor of cysteine proteinases from human polymorphonuclear granulocytes". Hoppe-Seyler's Zeitschrift für Physiologische Chemie. 364 (11): 1481–6. doi:10.1515/bchm2.1983.364.2.1481. PMID 6689312.
  6. ^ van Wyk SG, Du Plessis M, Cullis CA, Kunert KJ, Vorster BJ (November 2014). "cysteine protease and cystatin expression and activity during soybean nodule development and senescence". BMC Plant Biology. 14: 294. doi:10.1186/s12870-014-0294-3. PMC 4243279. PMID 25404209.
  7. ^ Kocevar N, Obermajer N, Kreft S (September 2008). "Membrane permeability of acylated cystatin depends on the fatty acyl chain length". Chemical Biology & Drug Design. 72 (3): 217–24. doi:10.1111/j.1747-0285.2008.00693.x. PMID 18702630. S2CID 24573152.

Further reading

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