Cloning and chromosomal mapping of the human gene of neuroglycan C (NGC), a neural transmembrane chondroitin sulfate proteoglycan with an EGF module.

Neuroglycan C (NGC) is a 150 kDa transmembrane chondroitin sulfate proteoglycan with a 120 kDa core glycoprotein that was originally isolated from the developing rat brain. A rabbit antiserum, raised against a recombinant polypeptide representing a protein of the rat NGC core protein, recognized an NGC homolog in homogenates of brains of various vertebrates including humans. Because of the possible involvement of this proteoglycan in the etiology of a human neuronal disease, we cloned a complete coding sequence from a human brain cDNA library using a rat NGC cDNA as a probe. The predicted protein contains 539 amino acids and shows 86% homology with the rat counterpart. The domain structure characteristic of rat NGC was completely conserved in human NGC, which consisted of an N-terminal signal sequence, a chondroitin sulfate-attachment domain, an acidic amino acid cluster, an EGF-like domain, a transmembrane domain and a cytoplasmic tail. Northern blot analysis revealed that a single transcript of 2.4 kb was detectable in the brain, but not in other human tissues. By fluorescence in situ hybridization (FISH) analysis, the human NGC gene was assigned to the chromosomal 3p21.3 band, where the Sotos syndrome has been mapped. Involvement of the NGC gene in the etiology of the Sotos syndrome remains to be examined.