Beta-lactoglobulin is the major whey protein in the milk of ruminants and is expressed in the mammary gland during pregnancy and lactation. Two types of beta-lactoglobulins were identified and isolated from horse colostrum: beta-1gI and beta-1gII. DNA sequence analysis of one of these showed that the gene is 4900 bases long and contains seven exons. It codes for a protein of 180 amino acid residues, containing an 18-residue signal peptide, within exons I to VI; exon VII is non-coding. Ali and Clark's data showed that the genes encoding serum retinol binding protein, major urinary protein, alpha-1-acid glycoprotein and apolipoprotein D have similar organization of exons and introns to beta-lactoglobulin. In particular, a comparison between beta-lactoglobulin and retinol binding protein shows that both genes encode equivalent elements of three-dimensional protein structure within analogous exons(Ali & Clark, 1988). The structural homology with human retinol-binding protein suggest a common origin of beta-lactoglobulin and human retinol-binding protein and imply that beta-lactoglobulins may be involved in the metabolism of retinol,in other words the transport and uptake of vitamin A in suckling animals. (Godovac-Zimmermann, et al,1985).

The amino acid sequences of both RBP and the Biliverdin binding protein from Manduca sexta were known before their x-ray structure determination. But the weak sequence homology of 17% identity between these two proteins was not recognized as significant until the similarity of their x-ray structures had been revealed(Branden & Tooze,1991).

Also, the amino acid sequence homology between humn RBP and bovine beta-lactoglobulin didn't draw attention either until their protein structures are discovered.

Here we learn the significance of combined approach of amino acid sequences and three-dimentional structures. Weak amino acid sequence similarities are not significant by themselves. However when combined with a three dimentional structure they can become significant and give important biological information if the sequence similarity conserves crucial structural properties.