About Kallikrein / KLK:
Kallikreins are a subgroup of serine proteases, enzymes that are found in the pancreas and are capable of cleaving peptide bonds in proteins. In total, there is a family of 15 serine proteases, labelled from KLK1 to KLK15, as well as the KLKB1 protein that has no known paralogue. Similar enzymes have since been located in biological fluids of humans.
Kallikreins are primarily split into two categories: plasma kallikrein and tissue kallikrein.
Plasma kallikrein is homologous to factor XI. It consists of four apple domains and one serine protease domain while KLKB1 is located on chromosome 4q34-35. The gene is activated by proteolytic processing facilitated by stimuli such as factor XII and PRCP. Bradykinin and kallidin kinins are released from the kininogens by the Plasma kallikrein, generating plasmin from plasminogen. Subsequently, plasma kallikrein is crucial for the regulation of blood pressure as well as inflammation.
The 15 tissue kallikreins (KLK1 to KLK15) are secreted throughout the human body, with different genes providing contrasting roles. KLK1, KLK2, and KLK12 are similar to KLKB1 as they activate the bradykinin. Meanwhile, KLK2 – 5 and KLK14 hydrolyse seminogelin to regulate semen liquefaction. KLK6 and KLK8 are linked to neuronal plasticity in the central nervous system. Skin desquamation are controlled by the KLK5, KLK7 and KLK14 genes that cleave cellular adhesion proteins.
Genes KLK1 to KLK15 also carry the protein names hK1 to hK15 and each have unique descriptions. For example, hK4 is a human kallikrein 4 complex with zinc, cobalt ions and benzamidine.
Kallikreins are enzymes that act upon a kininogen molecule to release bioactive peptide (kinen), which is why peptidases are viewed by researchers as potential biomarkers for cancer. Kininogen deficiency in humans does not manifest a clinical ab-normality in blood coagulation but contract proteins are needed for thrombus formation. Meanwhile, human glandular kallikrein (hK2) are used as tumour markers in relation to prostate cancer.
All genes within the KLK family are localised to chromosomal region 19q13.4 while they all use a catlytic triad of histidine, aspartic acid, and serine. Intron phases are fully conserved across all kallikreins while sequence homologies or DNA and acid levels fall between 40–80%. Regulation of homeostatic functions is controlled by catalyse the activation of kallikreins by other kallikreins.
Prekallikrein, which was discovered three decades after KLKB1, is the precursor of plasma kallikrein and is homologous to factor XI. It contains four apple domains and a catalytic serine protease domain. Interactions between PK and the kallikrein family of proteins are evident in the regulation of blood pressure.
Hereditary deficiencies of PK are uncommon but can be seen in patients suffering from sickle cell disease, DIC, or infection. It has been suggested that the mucosal bleeding can cause recurrent pregnancy loss too. KLKs function in a range of physiological roles and are deemed partly responsible for homeostatic functions.