The albumin multigene family encodes proteins synthesized in the liver
and secreted in the serum to fulfill ligand-carrier functions. The al
bumin (ALB), alpha(1)-fetoprotein (AFP), and vitamin D-binding protein
genes are syntenic, the ALB and AFP genes are organized in tandem, an
d the AFP gene is selectively expressed in the fetal liver. We how rep
ort the existence of a fourth member of the albumin gene family, locat
ed 10 kilobases downstream from the AFP locus. The new gene, named alp
ha-albumin (alpha ALB), is selectively expressed in the liver at late
stages of development. The alpha ALB mRNA sequence encodes a predicted
secreted protein with the typical triple domain disulfide cross-linke
d structure. Comparisons of coding and promoter sequences suggest that
alpha ALB could be a phylogenetic intermediate between the ALB and AF
P genes. The developmental switch between alpha ALB gene activation an
d AFP gene repression suggests new regulatory interplays at the albumi
n locus and adult stage-specific ligand binding functions carried out
by the alpha ALB gene product.