Coding

Part:BBa_K4165083

Designed by: Mennatallah Mahmoud Mohamed Abdelzaher Turky   Group: iGEM22_CU_Egypt   (2022-09-30)


SPINT3 (Serine Peptidase Inhibitor Kunitz type 3).

This basic part encodes Human serine protease inhibitor known as SPINT3 which is able to inhibit serine peptidases, like HtrA1 (BBa_K4165004).


Usage and Biology

This type of family encodes for a type of inhibitor that is able to inhibit serine proteases and it is predicted to be located extracellularly which interferes with the TGF-β signalling pathway. The inhibitor binds to trypsin-like (serine) proteases and since the catalytic core of HtrA1 (BBa_K4165004) is considered as a tyrpsin-like catalytic domain, so this inhibitor also is considered to inhibit the function of HtrA1 [1] - [4].


Sequence and Features


Assembly Compatibility:
  • 10
    INCOMPATIBLE WITH RFC[10]
    Illegal PstI site found at 7
  • 12
    INCOMPATIBLE WITH RFC[12]
    Illegal PstI site found at 7
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal BglII site found at 87
  • 23
    INCOMPATIBLE WITH RFC[23]
    Illegal PstI site found at 7
  • 25
    INCOMPATIBLE WITH RFC[25]
    Illegal PstI site found at 7
  • 1000
    COMPATIBLE WITH RFC[1000]


Functional Parameters

GC Content% Isoelectric point (PI) Charge at pH 7 Molecular Weight (Protein)
52.1% 6.155 -0.554 10.252 kDa

Dry Lab Characteriztion

Modeling

This inhibitor was modeled by several software and the top model was acquired from Alphafold2

                 Figure 1.: A graphical illustration showing the structure of the inhibitor (AlphaFold).

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.

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