| The cystatin superfamily is a well-established family of cysteine protease inhibitors. Cystatins A and B (type 1) are mainly intracellular; cystatins C, D, E/M, F, G, S, SN and SA cystatins are extracellular (type 2); and the kininogens are type 3 cystatins which are intravascular proteins. All true cystatins inhibit cysteine peptidases of the papain family, such as cathepsins, and some also inhibit legumain family enzymes. Cystatin SA, cystatin S and cystatin SN are found primarily in saliva. Cystatin S and SN can also be expressed in tears, urine and seminal fluid. Cystatin C is a related protein which is expressed in brain, thymus, ovary, epididymis and vas deferens. Cystatin D protects against proteinases in the oral cavity, while Cystatin E/M and F moderate the inhibition of cathepsin proteins. The fetuins, part of the cystatin superfamily, are secretable proteins that influence osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors and the response to systemic inflammation. High molecular weight kininogen (Kininogen HC) and low molecular weight kininogen (Kininogen LC) have varied roles, though they both inhibit the thrombin- and plasmin-induced aggregation of thrombocytes. |
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