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 recycling of immature GlcNAc-bearing thyroglobulin molecules through the Golgi back to the apical membrane for further processing until maturation is achieved. This process, which we call "receptor-mediated exocytosis," prevents lysosomal degradation of thyroid prohormones. In the present study, we report cloning of the cDNA encoding the (or one of the) monomer(s) constituting the human GlcNAc thyroid receptor. This novel gene, called NAGR1, was assigned by in situ hybridization to subbands p13.3-p13.2 of chromosome 19. Northern blot analysis showed that 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, skeletal muscle, kidney, and pancreas. The deduced amino acid sequence comprised a 51-kDa type I membrane protein with a single spanning region 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 repeats 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 studies is discussed.
Blanck
O
O
Laboratoire de Biochimie, URA 1455, Marseille, France.
Perrin
C
C
Mziaut
H
H
Darbon
H
H
Mattei
M G
MG
Miquelis
R
R
D000117:Acetylglucosamine / Q000378:metabolism*; D000236:Adenoma / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002277:Carcinoma / Q000737:chemistry / Q000145:classification; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004705:Endocytosis; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000032:analysis; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D034781:Receptors, N-Acetylglucosamine; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology; D013964:Thyroid Neoplasms / Q000737:chemistry
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; C440104:HNRNPM protein, human; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D034781:Receptors, N-Acetylglucosamine; D011988:Receptors, Thyroid Hormone; D013954:Thyroglobulin; D002118:Calcium; D000117:Acetylglucosamine