CDC50A

CDC50A is a conserved transmembrane protein that functions as a non-catalytic subunit required for the activity of P4-ATPases, a family of phospholipid flippases. In eukaryotes, CDC50A forms obligate complexes with P4-ATPases such as ATP8A1, ATP8A2, and ATP11 family members, and in yeast with Drs2p. The CDC50A-containing complexes drive the inward movement of specific phospholipids, notably phosphatidylserine and phosphatidylethanolamine, across membranes, helping to establish and maintain membrane lipid asymmetry essential for vesicle trafficking, membrane curvature, and protein sorting.

Structure and localization: CDC50A is a small transmembrane protein that localizes to the Golgi apparatus, endosomes, and the plasma membrane in various cell types. It contains luminal domains that mediate interaction with the catalytic P4-ATPase subunits, stabilizing them and enabling their trafficking from the endoplasmic reticulum to their functional membranes.

Genomics and evolution: The CDC50 protein family is conserved across fungi, animals, and plants, with CDC50A representing a vertebrate paralog that partners with multiple P4-ATPases.

Clinical relevance: Disruption of CDC50A-containing flippase complexes in model organisms leads to defects in membrane trafficking and lipid asymmetry. In humans, dysregulation of P4-ATPase/CDC50A complexes has potential implications for cellular processes such as vesicular transport and membrane remodeling, but specific disease associations require further study.