ECP has homology to pancreatic ribonuclease and has the ability to degrade RNA [20] . The amino acid sequence of ECP has eight cysteine residues spaced all throughout the peptide establishing the tertiary structure of the protein by the formation of four cysteine double bonds. Two catalytic residues, a lysine and a histidine, responsible for the RNA degradation have been identified, K38 and H128 [20, 21] (Figure 2 ) and these residues together with the cysteines are present in all members of the pancreatic ribonuclease family [20] . Analysis of the crystal structure of ECP verified this relationship to these other members of RNase family; namely a β-sheet backbone and three α-helices [22] . In a grove between two of the alpha helices the catalytic site for RNA degradation is located, with ECP showing a preference for cleaving poly-U RNA but not doublestranded RNA [23] . ECP consists of a single-chain peptide of 133 a.a. containing three sites for N-linked glycosylation, a.a.'s 57-59, 65-67 and 92-94 [24] (Figure 2 ). The glycosylation is composed of sialic acid, galactose A. Blood, negative control B. Blood positive, ECP Figure 2 The RNASE3 (ECP) gene and ECP protein sequence with numbers referring to the amino acid sequence. Below the protein sequence is a schematic diagram of the peptide sequence where the beta sheet domains and the alpha helix domains are shown as red arrow and green barrel structures, respectively. Amino acids involved in RNase activity are represented by scissors. Amino acids involved in membrane interference, heparin binding and bactericidal activity are represented by red arrows. Glycosylated amino acids are represented with a glycomoiety while the letter N highlights the nitrated amino acid. A blue box shows the site of the amino acid altering polymorphism rs2073342. and acetylglucosamine [25] explaining the variation in its detected size by Western blot of between 16 and 22 kDa [26] . Nineteen arginine residues facing the outside of the protein giving rise to the proteins basicity (pI > 11) [27] and possibly also its extraordinary stability compared to other ribonucleases [28] . In the presence of H 2 O 2 ECP can be nitrated on tyrosine Y33 by EPO. This inflammation-independent nitration occurs during granule maturation and was suggested to enhance interactions after secretion between several of the otherwise repulsive, positively charged granule proteins ( Figure 2 ) [29] . ECP has been shown to interact with artificial lipid membranes [30] and two tryptophan residues, W10 and W35 facing the outside, similar to the present arginine's, have been associated with this lipid membrane interaction [31] . ECP also has RNase independent cytostatic activity on tumour cells and the tryptophan residues contribute to this activity [32] . W35 was additionally found necessary for killing gram negative and gram positive bacteria [31] . The tryptophan's also facilitate ECP binding to heparin [33, 34] . Another study found that the residues R34, W35, R36 and K38, all part of loop 3 (a.a.'s 32-41) contributed to heparin binding and cytotoxicity [35] (Figure 2) . Surprisingly, when purified from granules of circulating cells, large quantities of the protein were found to lack cytotoxic activity [36] . ECP has not, like EPX/EDN, been found have alarmin activity, stimulating dendritic cells during Th2 immune responses [37] , but ECP has the ability to bind lipopolysaccharide (LPS) and other bacteria cell wall components [38] which might have a priming influence on the immune system. The binding of LPS was mainly attributed to a.a.'s 1 to 45 [39] . The 1 to 45 a.a. region was found to retain bactericidal activity as well as membrane destabilization activity. One commonly occurring polymorphism in the gene is leading to the replacement of an arginine residue with a threonine, R97T [40] ( Figure  2) . The a.a. alteration reduced ECP cytotoxicity to the cell line NCI-H69 assessed by using both recombinant protein [36] and pools of naive protein variants [41] . RNase activity was however not influenced by the R97T alteration. Deglycosylation of the recombinant T97 restored the proteins cytotoxicity suggesting that glycosylation are responsible for this inhibitory role.