The albumin multigene family encodes proteins synthesized in the liver and secreted in the serum to fulfill ligand-carrier functions. The albumin (ALB), alpha 1-fetoprotein (AFP), and vitamin D-binding protein genes are syntenic, the ALB and AFP genes are organized in tandem, and the AFP gene is selectively expressed in the fetal liver. We now report the existence of a fourth member of the albumin gene family, located 10 kilobases downstream from the AFP locus. The new gene, named alpha-albumin

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... (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-linked structure. Comparisons of coding and promoter sequences suggest that alpha ALB could be a phylogenetic intermediate between the ALB and AFP genes. The developmental switch between alpha ALB gene activation and AFP gene repression suggests new regulatory interplays at the albumin locus and adult stage-specific ligand binding functions carried out by the alpha ALB gene product.