Coding
EDN

Part:BBa_K3647555

Designed by: Natalia Savinkova, Ida Berghten, Astrid Welin, Thalia Rodriquez, Osamudiamen Iyere, Frida Haugskott, Oliver Hild Walett   Group: iGEM20_Linkoping   (2020-08-25)

Eosinophil-derived neurotoxin (N-term. 6XHIS, TEV)
For information and characterization of this part please see: BBa_K3647444

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal BamHI site found at 109
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]

General info

Eosinophil-derived neurotoxin (EDN), is encoded by the RNASE2 gene located on the long arm of chromosome 14. EDN is a non-secretory ribonuclease that functions as an endogenous antiviral agent and is located in eosinophil granulocytes. EDN is very closely related to ECP and has a homology of 89%. (Rosenberg, 2012).

EDN is secreted after activation by cytokines or other pro-inflammatory mediators (Boix, 2015), and the antiviral and neurotoxic activity results in a reduction of the activity of single-stranded RNA viruses, and also attracts immune cells when released. (Baker, 2006)

Figure 1. Structure of Eosinophil-derived neurotoxin. PBD code 1GQV.


EDN is a 16.04 kDa single-chain protein with 135 amino acids, and a member of the pancreatic ribonuclease superfamily (Baker, 2006). EDN has eight cysteines that form four specific disulfide bonds that are characteristic for all enzymatically active ribonucleases, and histidine 15, 129 together with lysine 38 forms the catalytic site. (Rosenberg, 2015)

Eosinophilic derived neurotoxin (EDN) is one of the four major proteins found in the cytoplasmic granules of human eosinophilic leukocytes, cells that are mobilized from the bone marrow to the blood and tissues in response to Th2 stimuli characteristic of allergic inflammation and parasitic helminth infection.

Regardless of the asthma phenotype, when eosinophils are activated either by infection, allergy, they release EDN. This indicates that EDN levels can be used in the diagnosis and monitoring of different asthma phenotypes for example chronic cough, eosinophilic bronchitis, etc. Several studies have shown a correlation between patients with asthma and higher increased levels of EDN. Eosinophils are key cells in the airway inflammation of SA and associated with persistent elevation of type 2 inflammatory markers. Studies have suggested that the serum EDN level is a useful serum biomarker for assessing the severity of SA in adult asthmatics. The serum EDN level was significantly higher in patients with SA (severe asthma) than in those with NSA (non-severe asthma) (Lee, 2019)

In children who are too young to fully participate in/cooperate with lung function tests, EDN levels may be useful as an alternative measurement of eosinophilic inflammation. Overall, EDN is a very accurate biomarker for the pathophysiology of the disease asthma due to its measure of the secretory activity of eosinophils. (Kim, 2013)


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