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Gene Review

Klk1b3  -  kallikrein 1-related peptidase b3

Mus musculus

Synonyms: 7S nerve growth factor gamma chain, Gamma-NGF, Glandular kallikrein K3, Kallikrein 1-related peptidase b3, Klk-3, ...
 
 
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Disease relevance of Klk1b3

  • Finally, in gamma-NGF the autolysis loop, found in the carboxyl terminal region, functions to lower the Km kinetic constant for a variety of substrates [1].
 

High impact information on Klk1b3

 

Biological context of Klk1b3

  • Using the epidermal growth factor binding protein (mGK-9) and the gamma-subunit of nerve growth factor (mGK-3), as test cases, mature processed forms, obtained as functionally active proteins, as well as various precursor forms, were isolated [5].
  • The conformations of three of the six loops surrounding the active site are relatively well defined in the models of gamma-NGF and EGF-BP, but three other loops are likely to have flexible conformations [6].
  • Although the amino acid sequence of alpha-NGF is closely related to those of gamma-NGF and EGF-BP, it is catalytically inactive [6].
  • In contrast, the kallikrein gene mGK-3, which shows a different response to thyroid hormone from that of mGK-6, showed no significant binding in the comparable promoter region [7].
 

Anatomical context of Klk1b3

 

Associations of Klk1b3 with chemical compounds

  • Specifically, loop 1, located in the amino terminal region (Bode, W., et al., J. Mol. Biol. 164, 237-282, 1983), in gamma-NGF enhanced the kcat for substrates containing threonine in the P2 position, as is the case during the processing of the carboxy terminus of the beta-NGF precursor [1].
 

Other interactions of Klk1b3

 

Analytical, diagnostic and therapeutic context of Klk1b3

  • Antibodies have been prepared against alpha-NGF and purified by affinity chromatography so that they do not cross-react with gamma-NGF [11].
  • Site-directed mutagenesis of alpha-NGF to alter the N-terminus and three residues in loop 7, a region that contributes to the catalytic center, restored substantial catalytic activity against N-benzoyl arginine-p-nitroanilide as substrate in two derivatives although they were not as active as recombinant gamma-NGF [13].

References

  1. Synthetic chimeras of mouse growth factor-associated glandular kallikreins. I. Kinetic properties. Blaber, M., Isackson, P.J., Burnier, J.P., Marsters, J.C., Bradshaw, R.A. Protein Sci. (1993) [Pubmed]
  2. Use of a cDNA recombinant for the gamma-subunit of mouse nerve growth factor to localize members of this multigene family near the TAM-1 locus on chromosome 7. Howles, P.N., Dickinson, D.P., DiCaprio, L.L., Woodworth-Gutai, M., Gross, K.W. Nucleic Acids Res. (1984) [Pubmed]
  3. beta-NGF-endopeptidase: structure and activity of a kallikrein encoded by the gene mGK-22. Fahnestock, M., Woo, J.E., Lopez, G.A., Snow, J., Walz, D.A., Arici, M.J., Mobley, W.C. Biochemistry (1991) [Pubmed]
  4. Substrate specificities of growth factor associated kallikreins of the mouse submandibular gland. Blaber, M., Isackson, P.J., Marsters, J.C., Burnier, J.P., Bradshaw, R.A. Biochemistry (1989) [Pubmed]
  5. The characterization of recombinant mouse glandular kallikreins from E. coli. Blaber, M., Isackson, P.J., Bradshaw, R.A. Proteins (1990) [Pubmed]
  6. Prediction of the three-dimensional structures of the nerve growth factor and epidermal growth factor binding proteins (kallikreins) and an hypothetical structure of the high molecular weight complex of epidermal growth factor with its binding protein. Bax, B., Blaber, M., Ferguson, G., Sternberg, M.J., Walls, P.H. Protein Sci. (1993) [Pubmed]
  7. Differential binding of thyroid hormone receptors to mouse glandular kallikrein gene promoters: evidence for multiple binding regions in the mGK-6 gene. Barlow, J.W., Raggatt, L.E., Drinkwater, C.C., Lyons, I.G., Richards, R.I. J. Mol. Endocrinol. (1989) [Pubmed]
  8. Synthesis and partial maturation of the alpha- and gamma-subunits of the mouse submaxillary gland nerve growth factor in Xenopus laevis oocytes. Wion, D., Dicou, E., Brachet, P. FEBS Lett. (1984) [Pubmed]
  9. The syntenic relationship of proximal mouse chromosome 7 and the myotonic dystrophy gene region on human chromosome 19q. Saunders, A.M., Seldin, M.F. Genomics (1990) [Pubmed]
  10. Structure of mouse 7S NGF: a complex of nerve growth factor with four binding proteins. Bax, B., Blundell, T.L., Murray-Rust, J., McDonald, N.Q. Structure (1997) [Pubmed]
  11. Expression of the alpha subunit of 7S nerve growth factor in the mouse submandibular gland. Isackson, P.J., Nisco, S.J., Bradshaw, R.A. Neurochem. Res. (1987) [Pubmed]
  12. Synthetic chimeras of mouse growth factor-associated glandular kallikreins. II. Growth factor binding properties. Blaber, M., Isackson, P.J., Holden, H.M., Bradshaw, R.A. Protein Sci. (1993) [Pubmed]
  13. Nerve growth factor alpha subunit: effect of site-directed mutations on catalytic activity and 7S NGF complex formation. Yarski, M.A., Bax, B.D., Hogue-Angeletti, R.A., Bradshaw, R.A. Biochim. Biophys. Acta (2000) [Pubmed]
 
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