Alternative titles; symbols
HGNC Approved Gene Symbol: KLK2
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38): 19:50,873,439-50,880,567 (from NCBI)
The glandular kallikreins are a distinct group of serine proteases with molecular masses of 25,000 to 40,000 and an ability to release vasoactive peptides from kininogen in vitro, although the kininogenase activity of different kallikreins is highly variable. The true physiologic role of specific kallikreins is often unrelated to the kininogenase activity. In the mouse a major site of kallikrein synthesis is the male submaxillary gland. Glandular kallikreins are also synthesized in the pancreas and kidney. The several kallikreins found in this tissue include epidermal growth factor-binding protein (EGF-BP) and the gamma subunit of nerve growth factor, which are responsible for the processing of EGF (131530) and NGF (162030), respectively. Although EGF-BP and NGFG exhibit strict substrate specificity, they share extensive amino acid sequence homology and immunologic crossreactivity. Mason et al. (1983) concluded that the glandular kallikrein gene family comprises 25 to 30 highly homologous genes that encode specific proteases involved in the processing of biologically active peptides. All are closely linked on mouse chromosome 7 (assignment by Chinese hamster-mouse hybrid cell studies). Several human kallikrein genes have been isolated.
Schedlich et al. (1987) described a human glandular preprokallikrein gene, GK1, isolated from a human genomic library. The 5.2-kb gene encodes a prepropeptide of 261 amino acids. The mature protein is 237 amino acids long and has 66% homology with the sequence predicted for the human kallikrein synthesized in pancreas, kidney, and salivary gland (KLK1; 147910). Seventy-three percent homology with human prostate-specific antigen (APS; 176820) was observed. Expression of the glandular kallikrein gene, like that of the APS gene, seems to be restricted to the prostate.
By searching for ESTs specifically expressed in normal prostate and prostate cancer, followed by PCR and sequence analysis, Liu et al. (1999) cloned a 3.0-kb splice variant of KLK2 that has a longer 3-prime UTR than the previously cloned 1.5-kb transcript. The proteins encoded by the 2 transcripts are identical. PCR and RNA dot blot analysis of several tissues detected the longer transcript only in prostate. Northern blot analysis suggested that the 3.0-kb transcript is expressed at about 25% of the level of the 1.5-kb transcript. Liu et al. (1999) also identified a splice variant that has a deletion of 13 nucleotides between exons 3 and 4, giving rise to a frameshift and an immediate translation stop. The deduced protein lacks 97 C-terminal amino acids.
Using RT-PCR, Gan et al. (2000) detected highest KLK2 expression in prostate, with lower levels in several other tissues.
David et al. (2002) identified an alternative KLK2 transcript, which they called KLK2-linked molecule (KLM), that arises from the use of an alternate donor site within intron 1. The transcript contains a sequence from intron 1 linked to exon 1. The deduced protein contains 141 amino acids and has a calculated molecular mass of 15 kD. KLM shares only the N-terminal 15-amino acid signal peptide with the original KLK2 protein; the mature proteins display no similarity. However, KLM shares 32% amino acid identity with a comparable KLK3 (176820) splice variant that David et al. (2002) designated PSALM. Both of these variants are rich in proline and serine/threonine residues. RT-PCR analysis showed prostate-specific expression of the KLM transcript.
Liu et al. (1999) stated that the KLK2 gene contains 5 exons.
Riegman et al. (1989) found that the glandular kallikrein gene and that for prostate-specific antigen are aligned in a head-to-tail orientation and are separated by about 12 kb. Southern blot analysis of DNA from a panel of human-hamster hybrid cells showed that the genes are situated on chromosome 19. Since the KLK1 gene is also on chromosome 19, these 3 genes probably represent a cluster. From in situ hybridization studies, Qin et al. (1991) concluded that the glandular kallikrein gene and probably other kallikrein genes are located in q13.3 and q13.4 bands of chromosome 19 and are probably near the border of these 2 bands.
By sequencing the kallikrein gene cluster on chromosome 19q13, Gan et al. (2000) identified 13 kallikrein-related genes and 5 pseudogenes.
The gamma subunit of Ngf in mouse is a kallikrein (Klk1b3) involved in the processing of Ngf (Mason et al., 1983). The mouse klk1b3 locus is situated on chromosome 7 where it cosegregates with the murine homologs of KLK1 (147910), LHB (152780), and RRAS (165090), all of which map to human chromosome 19q13.3 in a region of conserved synteny with mouse chromosome 7 (Saunders and Seldin, 1990).
David, A., Mabjeesh, N., Azar, I., Biton, S., Engel, S., Bernstein, J., Romano, J., Avidor, Y., Waks, T., Eshhar, Z., Langer, S. Z., Lifschitz-Mercer, B., Matzkin, H., Rotman, G., Toporik, A., Savitsky, K., Mintz, L. Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 gives rise to novel prostate-specific proteins. J. Biol. Chem. 277: 18084-18090, 2002. [PubMed: 11834722] [Full Text: https://doi.org/10.1074/jbc.M102285200]
Gan, L., Lee, I., Smith, R., Argonza-Barrett, R., Lei, H., McCuaig, J., Moss, P., Paeper, B., Wang, K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene 257: 119-130, 2000. [PubMed: 11054574] [Full Text: https://doi.org/10.1016/s0378-1119(00)00382-6]
Liu, X. F., Essand, M., Vasmatzis, G., Lee, B., Pastan, I. Identification of three new alternate human kallikrein 2 transcripts: evidence of long transcript and alternative splicing. Biochem. Biophys. Res. Commun. 264: 833-839, 1999. [PubMed: 10544017] [Full Text: https://doi.org/10.1006/bbrc.1999.1595]
Mason, A. J., Evans, B. A., Cox, D. R., Shine, J., Richards, R. I. Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature 303: 300-307, 1983. [PubMed: 6602295] [Full Text: https://doi.org/10.1038/303300a0]
Qin, H., Kemp, J., Yip, M.-Y., Lam-Po-Tang, P. R. L., Morris, B. J. Localization of human glandular kallikrein-1 gene to chromosome 19q13.3-13.4 by in situ hybridization. Hum. Hered. 41: 222-226, 1991. [PubMed: 1783409] [Full Text: https://doi.org/10.1159/000154005]
Riegman, P. H. J., Vlietstra, R. J., Klaassen, P., van der Korput, J. A. G. M., Geurts van Kessel, A., Romijn, J. C., Trapman, J. The prostate-specific antigen gene and the human glandular kallikrein-1 gene are tandemly located on chromosome 19. FEBS Lett. 247: 123-126, 1989. [PubMed: 2468530] [Full Text: https://doi.org/10.1016/0014-5793(89)81253-0]
Saunders, A. M., Seldin, M. F. A molecular genetic linkage map of mouse chromosome 7. Genomics 8: 525-535, 1990. [PubMed: 1981054] [Full Text: https://doi.org/10.1016/0888-7543(90)90040-2]
Schedlich, L. J., Bennetts, B. H., Morris, B. J. Primary structure of a human glandular kallikrein gene. DNA 6: 429-437, 1987. [PubMed: 2824146] [Full Text: https://doi.org/10.1089/dna.1987.6.429]