Biochem/physiol Actions

KLK3 (Kallikrein-3) is involved in important physiological roles such as blood pressure modulation, complement activation, and control and maintenance of inflammatory responses. It is a key component of the kinin-generating pathways (PK system) and in the surface-mediated “contact system”. Circulating plasma KLK3 is bound with the high molecular weight kininogen (HK) (PK.HK), and on endothelial cells this complex interacts with a multiprotein complex consisting of cytokeratin 1, urokinase-type plasminogen activator receptor, and gC1qR. This complex is involved in mediating complement, coagulation, and kinin cascades. PK.HK interaction with this multiprotein complex also results in prolylcarboxypeptidase-mediated activation of KLK3, which in turn cleaves HK to release bradykinin, converts factor XII (fXII) to active factor XIIa (fXIIa) and prorenin to renin, the key component in the renin-angiotensin system. KLK3b alleles are found to be associated with end-stage renal disease (ESRD) suggesting that variants in KLK3 gene might be linked with ESRD susceptibility.

General description

KLK3 (Kallikrein-3), or plasma kallikrein (PKK), is a serine protease which was first identified from Fletcher trait, a hereditary disorder characterized by an extended partial thromboplastin time which however becomes normal upon exposing of plasma to a clot-promoting surface. Kallikerin proteins are classified into two major groups, plasma kallikrein and tissue kallikreins. Human cDNA of KLK3 codes for a leader peptide of 19 residues and a 619-residue mature prekallikrein protein. The mature protein contains a 371-residue N-terminal heavy chain which is composed of four Apple domains, the homologues of which are also found in factor XI. Both the heavy and light chains are highly glycosylated, and the light chain can exist as 36- and 33-kDa isoforms due to variation in the carbohydrate moiety. KLK3 gene is localized to human chromosome 4q35. The encoded protein is synthesized in the liver as a proenzyme known as prekallikrein.

Physical form

Lyophilized from 0.22 µm filtered solution in 50 mM Tris, 150 mM NaCl, pH 7.5. Normally Mannitol or Trehalose is added as protectants before lyophilization.

Reconstitution

Centrifuge the vial prior to opening. Reconstitute in sterile PBS, pH 7.4 to a concentration of 50 µg/mL. Do not vortex. This solution can be stored at 2-8°C for up to 1 month. For extended storage, it is recommended to store at -20°C.