Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen. 2 H(+) + 2 superoxide = H2O2 + O2 Binds 1 copper ion per subunit. Binds 1 zinc ion per subunit. Homotetramer (PubMed:19289127). Directly interacts with ATP7A; this interaction is copper-dependent and is required for SOD3 activity (PubMed:16371425). 99% of EC-SOD is anchored to heparan sulfate proteoglycans in the tissue interstitium, and 1% is located in the vasculature in equilibrium between the plasma and the endothelium. Expressed in blood vessels, heart, lung, kidney and placenta. Major SOD isoenzyme in extracellular fluids such as plasma, lymph and synovial fluid. The variant Gly-231 which is found in about 2.2% of individual displays a 10-fold increased plasma EC-SOD content due to reduced heparin-binding affinity and thus the impairment of its binding ability to endothelial cell surface. Belongs to the Cu-Zn superoxide dismutase family. Superoxide dismutase entry