Cystatin A Explained

Cystatin-A is a protein that in humans is encoded by the CSTA gene.^{[1] [2]}

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins, and kininogens. This gene encodes a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer.

Interactions

Cystatin A has been shown to interact with Cathepsin B^{[3] [4]} and CTSL1.^{[4] [5]}

See also

• Peptide Transporter Carbon Starvation (cstA) Family

Further reading

• Järvinen M, Rinne A, Hopsu-Havu VK . Human cystatins in normal and diseased tissues--a review . Acta Histochem. . 82 . 1 . 5–18 . 1988 . 3122506 . 10.1016/s0065-1281(87)80043-0.
• Brown WM, Dziegielewska KM . Friends and relations of the cystatin superfamily--new members and their evolution . Protein Sci. . 6 . 1 . 5–12 . 1997 . 9007972 . 10.1002/pro.5560060102 . 2143511 .
• Kos J, Lah TT . Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review) . Oncol. Rep. . 5 . 6 . 1349–61 . 1998 . 9769367 . 10.3892/or.5.6.1349.
• Rinne A, Järvinen M, Räsänen O . A protein reminiscent of the epidermal SH-protease inhibitor occurs in squamous epithelia of man and rat . Acta Histochem. . 63 . 2 . 183–92 . 1979 . 107702 . 10.1016/s0065-1281(78)80024-5.
• Räsänen O, Järvinen M, Rinne A . Localization of the human SH-protease inhibitor in the epidermis. Immunofluorescent studies . Acta Histochem. . 63 . 2 . 193–6 . 1979 . 107703 . 10.1016/s0065-1281(78)80025-7.
• Rasmussen HH, van Damme J, Puype M . Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes . Electrophoresis . 13 . 12 . 960–9 . 1993 . 1286667 . 10.1002/elps.11501301199 . 41855774 . etal.
• Madsen P, Rasmussen HH, Leffers H . Molecular cloning, occurrence, and expression of a novel partially secreted protein "psoriasin" that is highly up-regulated in psoriatic skin . J. Invest. Dermatol. . 97 . 4 . 701–12 . 1991 . 1940442 . 10.1111/1523-1747.ep12484041 . etal.
• Hsieh WT, Fong D, Sloane BF . Bonnie Sloane. Mapping of the gene for human cysteine proteinase inhibitor stefin A, STF1, to chromosome 3cen-q21 . Genomics . 9 . 1 . 207–9 . 1991 . 2004763 . 10.1016/0888-7543(91)90241-6 . etal.
• Rinne A, Järvinen M, Dorn A . [Low-molecular cysteine protease inhibitors in the human palatal tonsil] . Anatomischer Anzeiger . 161 . 3 . 215–30 . 1986 . 2424340 . etal.
• Kartasova T, Cornelissen BJ, Belt P, van de Putte P . Effects of UV, 4-NQO and TPA on gene expression in cultured human epidermal keratinocytes . Nucleic Acids Res. . 15 . 15 . 5945–62 . 1987 . 2442723 . 10.1093/nar/15.15.5945 . 306060 .
• Takeda A, Kaji H, Nakaya K . Comparative studies on the primary structure of human cystatin as from epidermis, liver, spleen, and leukocytes . J. Biochem. . 105 . 6 . 986–91 . 1989 . 2768224 . 10.1093/oxfordjournals.jbchem.a122792. etal.
• Strauss M, Stollwerk J, Lenarcic B . Chemical synthesis of a gene for human stefin A and its expression in E. coli . Biol. Chem. Hoppe-Seyler . 369 . 9 . 1019–30 . 1989 . 3067731 . 10.1515/bchm3.1988.369.2.1019. etal.
• Davies ME, Barrett AJ . Immunolocalization of human cystatins in neutrophils and lymphocytes . Histochemistry . 80 . 4 . 373–7 . 1984 . 6429090 . 10.1007/BF00495420 . 13559202 .
• Machleidt W, Borchart U, Fritz H . Protein inhibitors of cysteine proteinases. II. Primary structure of stefin, a cytosolic protein inhibitor of cysteine proteinases from human polymorphonuclear granulocytes . Hoppe-Seyler's Z. Physiol. Chem. . 364 . 11 . 1481–6 . 1984 . 6689312 . 10.1515/bchm2.1983.364.2.1481. etal.
• Söderström KO, Laato M, Wu P . Expression of acid cysteine proteinase inhibitor (ACPI) in the normal human prostate, benign prostatic hyperplasia and adenocarcinoma . Int. J. Cancer . 62 . 1 . 1–4 . 1995 . 7541394 . 10.1002/ijc.2910620102 . 25265556 . etal.
• Tate S, Ushioda T, Utsunomiya-Tate N . Solution structure of a human cystatin A variant, cystatin A2-98 M65L, by NMR spectroscopy. A possible role of the interactions between the N- and C-termini to maintain the inhibitory active form of cystatin A . Biochemistry . 34 . 45 . 14637–48 . 1995 . 7578072 . 10.1021/bi00045a004 . etal.
• Martin JR, Craven CJ, Jerala R . The three-dimensional solution structure of human stefin A . J. Mol. Biol. . 246 . 2 . 331–43 . 1995 . 7869384 . 10.1006/jmbi.1994.0088 . etal.
• Steinert PM, Marekov LN . Direct evidence that involucrin is a major early isopeptide cross-linked component of the keratinocyte cornified cell envelope . J. Biol. Chem. . 272 . 3 . 2021–30 . 1997 . 8999895 . 10.1074/jbc.272.3.2021 . free .

External links

• Cystatin: a protein that flips out! QUite Interesting PDB Structure article at PDBe
• The MEROPS online database for peptidases and their inhibitors: I25.001

Notes and References

1. Hsieh WT, Barrick JL, Berrettini WH, Chan MM, Fong D . A PstI DNA polymorphism in the human stefin A gene (STF 1) . Nucleic Acids Res . 19 . 7 . 1722 . Jun 1991 . 1674139 . 333958 . 10.1093/nar/19.7.1722-a .
2. Web site: Entrez Gene: CSTA cystatin A (stefin A).
3. Pavlova . Alona . Björk Ingemar . Sep 2003 . Grafting of features of cystatins C or B into the N-terminal region or second binding loop of cystatin A (stefin A) substantially enhances inhibition of cysteine proteinases . Biochemistry . 42 . 38 . 11326–33 . United States. 0006-2960. 14503883 . 10.1021/bi030119v .
4. Estrada . S . Nycander M . Hill N J . Craven C J . Waltho J P . Björk I . May 1998 . The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L . Biochemistry . 37 . 20 . 7551–60 . UNITED STATES. 0006-2960. 9585570 . 10.1021/bi980026r .
5. Majerle . Andreja . Jerala Roman . Sep 2003 . Protein inhibitors form complexes with procathepsin L and augment cleavage of the propeptide . Arch. Biochem. Biophys. . 417 . 1 . 53–8 . United States. 0003-9861. 12921779 . 10.1016/S0003-9861(03)00319-9 .