Part:BBa_K4165082

SPINK9 (Serine Peptidase Inhibitor Kazal type 9).

This basic part encodes Human serine protease inhibitor known as SPINK9 which is able to inhibit trypsin-like proteases, like HtrA1 (BBa_K4165004).

Usage and Biology

This part encodes for a type of inhibitor that is able to inhibit serine proteases and it is predicted to be located extracellularly. The main function of the inhibitor is to specifically target kallikrein-related peptide 5 (KLK-5) which is an important initiator of skin peeling. The inhibitor binds to trypsin proteases and since the catalytic core of HtrA1 (BBa_K4165004) is considered as a trypsin-like catalytic domain, so this inhibitor also is considered to inhibit the function of HtrA1 [1] - [4].

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

PDB Structure

Only a predicted model (AlphaFold).

AlphaFold: https://alphafold.ebi.ac.uk/entry/Q5DT21 Molprobity: Clash Score: Ramachandran Favoured: Ramachandran Outliers: Rotamers Outliers: C-beta Deviations: Q-Mean:

                 Figure 1.: A graphical illustration showing the domains of TRIM21.

References

1 - Frochaux, V., Hildebrand, D., Talke, A., Linscheid, M. W., & Schlüter, H. (2014). Alpha-1-antitrypsin: a novel human high temperature requirement protease A1 (HTRA1) substrate in human placental tissue. PloS one, 9(10), e109483.
2 - Grau, S., Baldi, A., Bussani, R., Tian, X., Stefanescu, R., Przybylski, M., ... & Ehrmann, M. (2005). Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proceedings of the National Academy of Sciences, 102(17), 6021-6026.
3 - Eigenbrot, C., Ultsch, M., Lipari, M. T., Moran, P., Lin, S. J., Ganesan, R., ... & Kirchhofer, D. (2012). Structural and functional analysis of HtrA1 and its subdomains. Structure, 20(6), 1040-1050.
4 - Chen, T. J., Tian, Y. F., Chou, C. L., Chan, T. C., He, H. L., Li, W. S., ... & Lai, H. Y. (2021). High spink4 expression predicts poor outcomes among rectal cancer patients receiving CCRT. Current Oncology, 28(4), 2373-2384.