Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatidylserine externalization on the cell surface (PubMed:9218461, PubMed:8663431, PubMed:10770950, PubMed:9572851, PubMed:9485382, PubMed:18629440, PubMed:23590222, PubMed:24648509, PubMed:24343571, PubMed:32110987, PubMed:23659204, PubMed:29748552). Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with TRPC5 (By similarity). Also exhibits magnesium-dependent nuclease activity against double-stranded DNA and RNA but not single-stranded DNA and can enhance DNA decatenation mediated by TOP2A (PubMed:27206388, PubMed:17567603). Negatively regulates FcR-mediated phagocytosis in differentiated macrophages (PubMed:26745724). May contribute to cytokine-regulated cell proliferation and differentiation (By similarity). May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes (PubMed:15308695). Acts as an attachment receptor for HCV (PubMed:21806988). a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) Magnesium. Can also use zinc with lower efficiency. Activated by Pb(2+) and Hg(2+) ions (PubMed:23659204, PubMed:29748552). Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis (PubMed:10770950). Optimum pH is 8.0-9.0 for nuclease activity. Optimum temperature is 37 degrees Celsius for nuclease activity (PubMed:27206388). Activity reduced significantly beyond 45 degrees Celsius (PubMed:27206388). Forms homooligomers in the presence of calcium (PubMed:24648509). Interacts with ABL (PubMed:11390389). Interacts with RELT, RELL1 and RELL2 (PubMed:22052202). Interacts with OXSR1 in the presence of RELT (PubMed:22052202). Interacts with TOP2A and TOP2B (PubMed:17567603). Interacts with OCLN (PubMed:21806988). Interacts with TRPC5 (PubMed:32110987). Interacts with TRPC1 and TRPC4 (By similarity). (Microbial infection) Interacts with hepatitis C virus E1 and E2 glycoproteins. Localizes to the perinuclear region in the presence of RELT (PubMed:22052202). Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus (PubMed:12564925). Expressed in platelets, erythrocyte membranes, lymphocytes, spleen, thymus, prostate, testis, uterus, intestine, colon, heart, placenta, lung, liver, kidney and pancreas. Not detected in brain and skeletal muscle. (Microbial infection) Induced by IFNB1/IFN-beta in response to a viral infection. Up-regulated during PMA-induced differentiation of the monocytic cell line THP-1. The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity. The transmembrane domain is essential for membrane insertion, phospholipid scramblase activity and proper calcium-binding. Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis (PubMed:10770950). Phosphorylated by OXSR1 in the presence of RELT. Palmitoylation is required for its phospholipid scramblase activity (PubMed:9572851). Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus (PubMed:12564925). Belongs to the phospholipid scramblase family. Scramblase entry