Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin. Activated by calcium which induces conformational changes and interaction between the N-terminal regulatory region and the C-terminal catalytic region. Inhibited by diphenylene iodonium. Mainly expressed in pachytene spermatocytes of testis and in lymphocyte-rich areas of spleen and lymph nodes. Isoform v1 is expressed in spleen. Isoform v2 is expressed in testis. Also detected in ovary, placenta, pancreas, cardiac fibroblasts. Expressed in B-cells and prostate malignant cells. Isoform v1 and isoform v3 are expressed in epithelial colorectal adenocarcinoma cells. Isoform v2 and isoform v4 are expressed in endothelial cells. Isoform v1, isoform v2, isoform v3 and isoform v4 are expressed in pulmonary artery smooth muscle cells. Isoform v2 and isoform v5 are expressed in microvascular endothelial cells (at protein level). Expressed in fetal tissues. Down-regulated by TGFB1. Isoform v1 and isoform v2 of this protein have four functional EF-hand calcium-binding domains. Isoform v3 and isoform v4 have the third EF-hand domain interrupted by an insert. Truncated N-terminus. Truncated N-terminus. Extended N-terminus.