Presence of hormonogenic and repetitive domains in the first 930 amino acids of bovine thyroglobulin as deduced from the cDNA sequence

Abstract

The sequence of the first 2831 nucleotides of bovine thyroglobulin mRNA has been determined from the analysis of a cDNA clone. Following a 41‐nucleotide 5′ untranslated sequence, a single open‐reading frame encoding 930 amino acids was observed. This corresponds to the aminoterminal third of thyroglobulin, preceded by a putative signal peptide of 19 amino acids. The protein sequence was found to be essentially made of the sevenfold repetition of a 60‐amino‐acid‐long building unit, interrupted at fixed positions by unrelated segments of variable length. The presence of an internal homology within the repetitive unit itself suggests that the 5′ region of the thyroglobulin gene has evolved from the initial duplication of a relatively short sequence, followed by the serial duplication of the resulting unit. The tyrosine residue at position five has been assigned an important hormonogenic function [Mercken, L., Simons, M.‐J. and Vassart, G. (1982) FEBS Lett. 149, 285–287]. This residue is flanked by sequence elements related to the repeated unit, suggesting that the hormonogenic domain evolved also from the basic ancestor sequence.

The complete structure of the rat thyroglobulin gene.

“…We subsequently discovered, comparing our partial sequence data with the sequence of the Tg mRNA in humans (6) and cows (7), that clone pRT27.15 stops at about 1 kilobase (kb) from the 5' end of Tg mRNA. We then isolated other cDNA clones (data not shown), and the one extending the most at the 5' end is clone pRT27.23, which ends at 450 nucleotides from the 5' end of the mRNA (Fig.…”

“…1), we have determined the nucleotide sequence of the restriction fragments hybridizing to rat Tg mRNA. We then compared our sequences with those at the 5' end of human (6) and bovine (7) mRNA. In our restriction fragments we found a sequence that corresponds to the first 200 nucleotides of both human and bovine mRNA (Fig.…”

“…Finally, the amino acid sequence encoded by the second exon reveals the presence of a sequence coding for a peptide (Asn-Ile-Phe-Gly-Tyr-GlnVal-Asp...) that also occurs in bovine and human Tg and represents a major site for thyroxine formation (4). This peptide is located very close to the amino terminus of the mature protein (6,7).…”

“…The primary structure of two sites where most of the thyroxine is formed (the hormonogenic sites) has been determined by direct protein sequencing (4,5), whereas most of the information on the primary structure of the protein has been deduced from the nucleotide sequence of portions of cDNA for human (6), bovine (7), and rat (8) Tg. The analysis of the protein and of the mRNA sequence has shown that the two major hormonogenic tyrosines are located at the extremities of the protein (6)(7)(8)(9). This paper presents an overall view of an entire Tg gene, the rat gene.…”

Evolutionary origin of cholinergic macromolecules and thyroglobulin.

“…5). The coding information for rat TG is distributed in 42 exons, most of which correlate with repetitive structural domains previously defined by protein sequences deduced from human, rat, and bovine TG cDNA (31,(39)(40)(41). The 5'-end half of this gene, including 32 exons and spanning >80 kb, encodes highly repetitive domains (38).…”