The following serum transport proteins are known to be evolutionary related [1,2,3]:

• Albumin (ALB), the main protein of plasma. It binds water, cations such as Ca++, Na+, K+, fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood.
• α-fetoprotein (AFP) (α-fetoglobulin). AFP is a fetal plasma protein which also binds various cations, fatty acids and bilirubin.
• Vitamin D-binding protein (VDB), also known as group-specific component or Gc-globulin. VDB binds to vitamin D and its metabolites as well as fatty acids.
• Afamin (or α-albumin), a protein whose biochemical role is not yet characterized.

Structurally, these proteins consist of two to seven homologous domains of about 190 amino acids. Each domain, consisting of 10 α-helices, is formed by two smaller subdomains and contains five or six internal disulfide bonds as shown in the following schematic representation [4].

                    +---+          +----+                        +-----+
                    |   |          |    |                        |     |
 xxCxxxxxxxxxxxxxxxxCCxxCxxxxCxxxxxCCxxxCxxxxxxxxxCxxxxxxxxxxxxxxCCxxxxCxxxx
   |                 |       |      |             |            ***|********
   +-----------------+       +------+             +---------------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern.

The signature pattern we derived is based on three conserved cysteines at the end of the domain. We built it in such a way that it can detect all 3 repeats in albumin and human afamin, the first two in AFP and the first one in VDB and rat afamin. We also developed a profile, which covers the entire albumin domain.

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