Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families.
The amino acid sequence of human thyroglobulin is known to enclose cysteine-rich repetitive regions. In this study, we report the existence of an eleventh type-1 repeat within the human thyroglobulin sequence, and we characterize the thyroglobulin type-1 repeat as a protein module. The 11 thyroglobulin type-1 repeats possessed the same number of cysteine residues (six in type A, four in the two type B repeats), a fairly constant number of residues between cysteines and a conserved sequence pattern. By scanning protein sequence databases, 29 proteins belonging to six different families were found to enclose at least one, and up to three, thyroglobulin type-1 repeats in their sequence. Although the repeat was present in numerous proteins possessing binding properties, an examination of the information available in the literature showed that a direct role of the repeat in protein-protein interaction has rarely been assessed. A distance analysis of the sequences indicated that all repeats segregate into four clusters of phylogenically close sequences. A consensus sequence of type-1 repeats was derived from sequence similarity analysis; it comprised a central core of conserved residues including two highly conserved motifs, QC and CWCV. The type-1 repeat from thyroglobulin was found to differ from several previously described cysteine-rich modules, in particular from the epidermal-growth-factor-like module with which it has sometimes been confused. Therefore, our results provide a complete characterization of the repeats which will help in the detection of these repeats in newly characterized proteins, a necessary step for understanding the structural/biological role of this module.
Molina
F
F
CNRS UMR 9921, Faculté de Pharmacie, Montpellier, France.
Bouanani
M
M
Pau
B
B
Granier
C
C
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D002417:Cattle; D016384:Consensus Sequence; D003545:Cysteine; D016208:Databases, Factual; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012984:Software; D013954:Thyroglobulin / Q000737:chemistry* / Q000235:genetics
D029845:Amphibian Proteins; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C504372:Spock1 protein, rat; C029967:nidogen; C027525:saxitoxin-binding protein, Rana catesbeiana; D013954:Thyroglobulin; D003545:Cysteine