Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families

Eur J Biochem. 1996 Aug 15;240(1):125-33. doi: 10.1111/j.1432-1033.1996.0125h.x.


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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amphibian Proteins
  • Animals
  • Carrier Proteins / chemistry
  • Cattle
  • Consensus Sequence
  • Cysteine*
  • Databases, Factual
  • Histocompatibility Antigens Class II / chemistry
  • Humans
  • Membrane Glycoproteins / chemistry
  • Mice
  • Molecular Sequence Data
  • Phylogeny
  • Proteoglycans / chemistry
  • Rats
  • Sequence Homology, Amino Acid
  • Software
  • Thyroglobulin / chemistry*
  • Thyroglobulin / genetics


  • Amphibian Proteins
  • Carrier Proteins
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • Proteoglycans
  • Spock1 protein, rat
  • nidogen
  • saxitoxin-binding protein, Rana catesbeiana
  • Thyroglobulin
  • Cysteine

Associated data

  • GENBANK/U05246
  • PIR/S33293
  • SWISSPROT/P01266
  • SWISSPROT/P04233
  • SWISSPROT/P08833
  • SWISSPROT/P09758
  • SWISSPROT/P14543