Complete structure of the human alpha-albumin gene, a new member of the serum albumin multigene family.
The nucleotide sequence of the human alpha-albumin gene, including 887 bp of the 5'-flanking region and 1311 bp of the 3-flanking region (24,454 in total), was determined from three overlapping lambda phage clones. The sequence spans 22,256 bp from the cap site to the polyadenylylation site, revealing a gene structure of 15 exons separated by 14 introns. The methionine initiation codon ATG is within exon 1; the termination codon TGA is within exon 14. Exon 15 is entirely untranslated and contains the polyadenylylation signal AATAAA. The deduced polypeptide chain is composed of a 21-amino-acid leader peptide, followed by 578 amino acids of the mature protein. There are seven repetitive DNA elements (Alu and Kpn) in the introns and 3-flanking region. The sizes of the 15 alpha-albumin exons match closely those of the albumin, alpha-fetoprotein, and vitamin D-binding protein genes. The exons are symmetrically placed within the three domains of the individual proteins, and they share a characteristic codon splitting pattern that is conserved among members of the gene family. The results provide strong evidence that alpha-albumin belongs to, and most likely completes with, the serum albumin gene family. Based on structural similarity, alpha-albumin appears to be most closely related to alpha-fetoprotein. The complete structure of this family of four tandemly linked genes provides a well-characterized approximately 200 kb locus in the 4q subcentromeric region of the human genome.
Nishio
H
H
Department of Biochemistry, University of California, Riverside 92521, USA.
Dugaiczyk
A
A
D000418:Albumins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D010582:Bacteriophage lambda; D001483:Base Sequence; D002503:Centromere; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D005810:Multigene Family; D017433:Protein Structure, Secondary; D012326:RNA Splicing; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics*; D016385:TATA Box; D014809:Vitamin D-Binding Protein / Q000737:chemistry; D000509:alpha-Fetoproteins / Q000737:chemistry
D000418:Albumins; D012709:Serum Albumin; D014809:Vitamin D-Binding Protein; D000509:alpha-Fetoproteins; C023442:alpha-albumin