Prominin-2 and Other Relatives of CD133

Several molecules related to prominin-1/CD133, which was first characterized as a marker of mouse neuroepithelial stem cells and human hematopoietic stem cells, have been identified in various species. In mammals, a second prominin gene, prominin-2, has been identified and characterized, whereas in nonmammalian species, up to three prominin genes are potentially expressed. The structural similarities between prominin-1 and prominin-2 are, to some extent, reflected by their biochemical properties; both proteins are selectively concentrated in specific plasma membrane subdomains that protrude into the extracellular space and are released in small extracellular membrane vesicles. In contrast to the apically confined prominin-1, prominin-2 is distributed in a nonpolarized apico-basolateral fashion in polarized epithelial cells and appears to be expressed in separate epithelial cells. Their distinctive localization in plasma membrane protrusions is a hallmark of prominins, validating the naming of the family after its first identified member. Insights into the distinctive and/or complementary roles of the two prominins may be obtained by analyzing the evolutionary history of these proteins and the characteristics of orthologs and paralogs in more distantly related species. In addition, the characterization of prominins may shed light on the still elusive function of CD133.