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J. Biol. Chem., Vol. 278, Issue 10, 8586-8596, March 7, 2003

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Characterization of Prominin-2, a New Member of the Prominin Family of Pentaspan Membrane Glycoproteins^*,

Christine A. Fargeas, Mareike Florek^§, Wieland B. Huttner^¶, and Denis Corbeil^§

From the  Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108 and ^§ Medical Clinic and Polyclinic I TU-Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany

Prominin/CD133 is a 115/120-kDa integral membrane glycoprotein specifically associated with plasma membrane protrusions in epithelial and non-epithelial cells including neuroepithelial and hematopoietic stem cells. Here we report the identification as well as molecular and cell biological characterization of mouse, rat, and human prominin-2, a 112-kDa glycoprotein structurally related to prominin (referred to as prominin-1). Although the amino acid identity between prominin-2 and prominin-1 is low (<30%), their genomic organization is strikingly similar, suggesting an early gene duplication event. Like prominin-1, prominin-2 exhibits a characteristic membrane topology with five transmembrane segments and two large glycosylated extracellular loops. Upon its ectopic expression in Chinese hamster ovary cells as a green fluorescent protein fusion chimera, prominin-2 was also found to be associated with plasma membrane protrusions, as revealed by its co-localization with prominin-1, suggesting a related role. Consistent with this, prominin-2 shows a similar tissue distribution to prominin-1, being highly expressed in the adult kidney and detected all along the digestive tract as well as in various other epithelial tissues. However, in contrast to prominin-1, prominin-2 was not detected in the eye, which perhaps explains why a loss-of function mutation in the human prominin-1 gene causes retinal degeneration but no other obvious pathological signs. Finally, we present evidence for the existence of a family of pentaspan membrane proteins, the prominins, which are conserved in evolution.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF508942, AF269062, AF128113, AF245303, AF245304, AF160970, AF373869, AF127935, AF197345, and AF406812.

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