Cystatins

Title: Cystatins
Literature References: Protein superfamily of endogenous cysteine proteinase inhibitors. All inhibit papain-type peptidases, including serveral cathepsins. Widely distributed in animals, plants, and protozoa; at least 12 cystatins have been identified in humans. Type 1 (cystatins A and B), also known as stefins, are intracellular, single-chain peptides of ~100 residues with no disulfide bonds or carbohydrate. Type 2, comprising the largest group, are extracellular, secreted proteins, typically 120-125 residues with 2 disulfide bonds; broadly distributed and found in most body fluids. Type 3, known as kininogens, q.v., are intravascular, multi-functional, glycosylated proteins of mol wt 60-120 kDa that also serve as kinin precursors. Discovery of a papain inhibitor in chicken egg white: K. Fossum, J. R. Whitaker, Arch. Biochem. Biophys. 125, 367 (1968). Sequence homologies and evolutionary relationship: W. Müller-Esterl et al., FEBS Lett. 191, 221 (1985). Review of physiological role in malignant progression and prognosis: J. Kos, T. T. Lah, Oncol. Rep. 5, 1349-1361 (1998). Reviews: A. J. Barrett, Biomed. Biochim. Acta 45, 1363-1374 (1986); M. Abrahamson et al., Biochem. Soc. Symp. 70, 179-199 (2003).
Derivative Type: Cystatin A
CAS Registry Number: 107544-29-6
Additional Names: Stefin A; CPI-A; acidic cysteine proteinase inhibitor
Literature References: Found primarily in epithelial cells and polymorphonuclear leukocytes; also occurs in amniotic fluid and tears. Purification from human epidermis: M. Järvinen, J. Invest. Dermatol. 72, 114 (1978); from human granulocytes: J. Brzin et al., Z. Phys. Chem. 364, 1475 (1983).
Properties: Mature human form is a single chain, non-glycosylated peptide containing 98 amino acid residues; mol wt 11.0 kDa. Isoelectric point: 4.5-4.7.
Derivative Type: Cystatin B
CAS Registry Number: 99194-04-4
Additional Names: Stefin B; CPI-B; NCPI; neutral cysteine proteinase inhibitor
Literature References: Broadly distributed in human cells and tissues; general cytosolic inhibitor to protect against leakage of lysosomal enzymes. Mutations in the cystatin B gene have been associated with progressive myoclonus epilepsy. Isoln from human spleen: M. Järvinen, A. Rinne, Biochim. Biophys. Acta 708, 210 (1982); from human liver: G. D. J. Green et al., Biochem. J. 218, 939 (1984). Review of role in Unverricht-Lundborg disease: A.-E. Lehesjoki, EMBO J. 22, 3473-3478 (2003).
Properties: Mature human form is a single chain, non-glycosylated peptide containing 98 amino acid residues; mol wt 11.2 kDa. Isoelectric point: 5.6-6.3.
Derivative Type: Cystatin C
CAS Registry Number: 91448-99-6
Additional Names: Post-g-globulin; g-CSF; g-trace
Literature References: Found ubiquitously in vertebrates; major extracellular cysteine peptidase inhibitor in mammals. Isoln from human CSF: J. Clausen, Proc. Soc. Exp. Biol. Med. 107, 170 (1961); from urine of patients with renal dysfunction: E. A. Butler, F. V. Flynn, J. Clin. Pathol. 14, 172 (1961). Identification as a cystatin: A. J. Barrett et al., Biochem. Biophys. Res. Commun. 120, 631 (1984). Review of biochemistry and clinical role: M. Mussap, M. Plebani, Crit. Rev. Clin. Lab. Sci. 41, 467-550 (2004); of efficacy as biomarker for glomerular filtration rate: G. Filler et al., Clin. Biochem. 38, 1-8 (2005). Clinical evaluation to predict risk of cardiovascular events in elderly patients: M. G. Shlipak et al., N. Engl. J. Med. 352, 2049 (2005).
Properties: Mature human form is a single chain, non-glycosylated peptide containing 120 amino acid residues; mol wt 13.3 kDa. Isoelectric point: 9.3. Electrophoretic mobility: g3 (agarose gel electrophoresis at pH 8.6). E1cm1% 9.1 (280 nm). Conc in plasma of healthy adults: 0.8 to 1.2 mg/l.
Therap-Cat: Cystatin C as diagnostic aid (renal function).
Cysteamine Cysteic Acid Cysteine Cystine Cytarabine

Proteinase inhibitor I25, cystatin
Salivary Cystatin from Ornithodoros moubata.png
Crystal structure of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata from PDB entry 3L0R.[1]
Identifiers
Symbol Prot_inh_cystat
Pfam PF00031
Pfam clan CL0121
InterPro IPR000010
SMART SM00043
PROSITE PDOC00259

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 strand. 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 know to mis-fold to form amyloid deposits and are implicated in several diseases.