PLSCR3
Domain
The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity.
Function
Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of the phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer membrane of the mitochondria (PubMed:14573790, PubMed:17226776, PubMed:18358005, PubMed:29337693, PubMed:31769662). Plays an important role in mitochondrial respiratory function, morphology, and apoptotic response (PubMed:12649167, PubMed:14573790, PubMed:17226776, PubMed:18358005). Mediates the translocation of cardiolipin from the mitochondrial inner membrane to outer membrane enhancing t-Bid induced cytochrome c release and apoptosis (PubMed:14573790, PubMed:17226776, PubMed:18358005). Enhances TNFSF10-induced apoptosis by regulating the distribution of cardiolipin in the mitochondrial membrane resulting in increased release of apoptogenic factors and consequent amplification of the activity of caspases (PubMed:18491232). Regulates cardiolipin de novo biosynthesis and its resynthesis (PubMed:16939411).
Post-translational modifications
Phosphorylation at Thr-21 by PKC/PRKCD upon apoptotic stimuli enhances phospholipid scramblase activity.
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.
Sequence Similarities
Belongs to the phospholipid scramblase family.
Tissue Specificity
Expressed in heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, uterus, small intestine and peripheral blood lymphocytes. Not detected in testis, brain and liver.
Cellular localization
- Mitochondrion membrane
- Single-pass type II membrane protein
- Mitochondrion inner membrane
- Single-pass type II membrane protein
- Nucleus
- 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.
Alternative names
Phospholipid scramblase 3, PL scramblase 3, Ca(2+)-dependent phospholipid scramblase 3, PLSCR3