The KLK6 gene is located on 19q chromosome, has a total length of 11.043 nt, and consists of 7 exons and 6 introns.

KLK6 pre-mRNA is subjected to alternative splicing. Six (6) variants had previously been detected, while another 6 transcripts have recently been identified by our research group (Adamopoulos et al., 2017). Furthermore, one more variant is predicted, based on similarity to 50 ESTs. Each of them has a different exon and intron structure. The main variant (variant A) consists of 7 exons and 6 introns. The first 2 introns do not include coding regions and compose the 5UTR. The other 11 variants range from 3 to 7 exons and 2 to 6 introns, while some of them bare similarity to each other. The structures of all variants are clearly illustrated in Figure 1.

Not detected so far.

Eight different isoforms of KLK6 protein have been detected, consisting of 244, 137, 120, 149, 42, 138 277, and 182 amino acid (aa) residues, respectively. The KLK6 gene encodes a single-chain pre-proenzyme, which is enzymatically inactive. After the removal of the signal peptide (16 aa) from the pre-proenzyme, an inactive proKLK is formed and secreted to the extracellular space, where it is finally transformed into the active KLK through further cleavage (Bayani & Diamandis, 2011).

KLK6 is highly expressed in cerebral cortex, tonsil, spleen, esophagus, kidney, fallopian tube and breast.

KLK6 is mainly localized to nucleoplasm, nuclear membrane and cytokinetic bridge.

KLK6 is a serine protease, involved in proteolytic cascades. KLK6 has been suggested to be autoactivated or activate other proKLKs. When activated, serine proteases are usually regulated by binding to serpins (serine protease inhibitors), which prompts to their inactivation. A preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position is detected in KLK6 substrate. Three amino acid residues (positions: 62, 106, and 197) constitute the catalytic triad in the main protein isoform (isoform 1, 244 aa) that is responsible for serine protease activity. An Asp residue at position 191 suggests a trypsin-like activity, while chymotrypsin activity is suggested by a loop similar to chymotrypsin 3D-structure. However, chymotrypsin activity is rejected by recent studies. KLK6 is activated against amyloid precursor protein, which is associated with Alzheimers disease, myelin basic protein, and casein. Furthermore, it participates in the degradation of extracellular matrix (ECM) proteins, namely fibronectin, laminin, vitronectin, laminin and collagen. It is involved in alpha-synuclein degradation and in the inhibition of its polymerization. This fact demonstrates the potential role of KLK6 in Parkinsons disease. Furthermore, KLK6 plays a role in cancer invasion and metastasis (Bayani & Diamandis, 2011).

No mutations have been detected.