MOLECULAR-CLONING, CDNA ANALYSIS, AND LOCALIZATION OF A MONOMER OF THE N-ACETYLGLUCOSAMINE-SPECIFIC RECEPTOR OF THE THYROID, NAGR1, TO CHROMOSOME 19P13.3-13.2

We have proposed that the GlcNAc thyroid receptor triggers selective r ecycling of immature GlcNAc-bearing thyroglobulin molecules through th e Golgi back to the apical membrane for further processing until matur ation is achieved. This process, which we call ''receptor-mediated exo cytosis,'' prevents lysosomal degradation of thyroid prohormones. In t he present study, we report cloning of the cDNA encoding the (or one o f the) monomer(s) constituting the human GlcNAc thyroid receptor. This novel gene, called NAGR1, was assigned by in situ hybridization to su bbands p13.3-p13.2 of chromosome 19. Northern blot analysis showed tha t the mRNA encoding NAGR1 was present as a single transcript of 2.1 kb in the thyroid, but not in the heart, brain, placenta, lung, liver, s keletal muscle, kidney, and pancreas. The deduced amino acid sequence comprised a 51-kDa type I membrane protein with a single spanning regi on and a short intracytoplasmic domain. Sequence analysis showed that NAGR1 is a glycine-, tryptophan-, and methionine-rich protein with no cysteine residues or glycosylation site. No sequence homology with any known cDNA or protein was noted. The extracellular domain is composed of 420 amino acids and contains a region of 204 residues showing 15 r epeats of 4 amino acids, each 1 having an acidic amino acid presumably involved in calcium coordination. The intracellular domain contained what appeared to be a tyrosine internalization signal. The usefulness of this clone in glycobiology, cell biology, and thyroid pathology stu dies is discussed. (C) 1994 Academic Press, Inc.