<p>A number of serum transport proteins are known to be evolutionarily related, including albumin, alpha-fetoprotein, vitamin D-binding protein and afamin [<cite idref="PUB00003407"/>, <cite idref="PUB00000582"/>, <cite idref="PUB00002857"/>]. Albumin is the main protein of plasma; it binds water, cations (such as Ca²⁺, Na⁺ and K⁺), fatty acids, hormones, bilirubin and drugs - its main function is to regulate the colloidal osmotic pressure of blood. Vitamin D-binding protein binds to vitamin D and its metabolites, as well as to fatty acids. The biological role of afamin (alpha-albumin) has not yet been characterised.</p><p>Alpha-fetoprotein (AFP) (alpha-fetoglobulin) is a foetal plasma protein that binds various cations, fatty acids and bilirubin [<cite idref="PUB00000777"/>, <cite idref="PUB00000778"/>]. The protein appears in the plasma of 4-week old foetuses, reaches its highest levels in the 12th-16th week of gestation, dropping to trace amounts after birth. It is also found at high levels in the plasma and ascitic fluid of adults with hepatoma [<cite idref="PUB00000572"/>].</p><p>The amino acid sequence contains a 19-amino acid signal peptide [<cite idref="PUB00004602"/>], and a 591-residue mature protein [<cite idref="PUB00000350"/>]. Fifteen regularly-spaced disulphide bridges generate a 3-domain folding structure, each domain containing ~190 amino acids, with 5 or 6 internal disulphide bonds, as shown schematically below. Sequence comparisons indicate that the greatest level of conservation resides in domain 3 and the lowest in domain 1 [<cite idref="PUB00000777"/>].</p><pre> +---+ +----+ +-----+ | | | | | |xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx | | | | | | +-----------------+ +-----+ +---------------+</pre><p>In addition to the monomeric form of AFP, dimeric and trimeric forms occur, which dissociate only on exposure to disulphide-reducing reagents, suggesting that polymer formation is mediated by inter-molecular disulphide bond formation [<cite idref="PUB00000572"/>].</p> Alpha-fetoprotein