Conserved and unique amino acid residues in the domains of the growth hormones. Flounder growth hormone deduced from the cDNA sequence has the minimal size in the growth hormone prolactin gene family.
Growth hormone (GH), prolactin (PRL), and placental lactogen (PL) constitute a protein family whose genes are considered to have evolved from a common ancestral gene. GHs isolated from various vertebrate species are known to possess highly conserved structural and functional features. In the present study we have cloned and sequenced flounder growth hormone (fGH) cDNA to predict the primary structure of the hormone. The preprotein of fGH is composed of 190 amino acids, and mature fGH is found to be extraordinarily small, having 171 or 173 amino acid residues. The estimated molecular masses of mature fGH are 19.4 to 19.7 kDa. This minimal size of fGH enabled an extended analysis of the essential domains and of amino acid residues required in hormone-specific activities. fGH conserves and shares 37 residues with 20 other vertebrate GHs. These common residues are seen to cluster in five distinct domains (GD1 to GD5). In human PL (hPL), which has low growth-promoting activity, 35 of these 37 residues are conserved, while the other 2 residues in the GD1 domain (Arg-16 and Leu-20) are replaced by Gln and Ala, respectively. In a less active variant of human GH, hGH-V, only 1 residue (His-21) of the 37 residues is replaced by Tyr. Besides these 3 residues, 6 other residues unique to the GHs and some PLs, that is, Ala-24 (GD1), Ser-54 (GD2), Ser-78 (GD3), Leu-106, Leu-116, and Asp-122 (GD4), appear to be important for specific binding of the GHs. The GD5 domain, at the carboxyl-terminal ends of the GHs is considered to be involved mainly in the formation and stabilization of GH molecules.
Watahiki
M
M
Department of Biochemistry, Mie University School of Medicine, Japan.
Yamamoto
M
M
Yamakawa
M
M
Tanaka
M
M
Nakashima
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005432:Flounder; D005796:Genes; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D010902:Pituitary Gland / Q000378:metabolism; D011388:Prolactin / Q000235:genetics*; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
D003062:Codon; D011388:Prolactin; D013006:Growth Hormone; D004247:DNA