title: A nucleotide insertion and frameshift cause albumin Kénitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges.
abstract: Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-597.
authors.affiliation: Dipartimento di Biochimica A. Castellani, Università di Pavia, via Taramelli 3B, I-27100 Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Minchiotti
authors.forename: M
authors.initials: M
authors.lastname: Campagnoli
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.forename: M E
authors.initials: ME
authors.lastname: Cosulich
authors.forename: M
authors.initials: M
authors.lastname: Monti
authors.forename: P
authors.initials: P
authors.lastname: Pucci
authors.forename: U
authors.initials: U
authors.lastname: Kragh-Hansen
authors.forename: B
authors.initials: B
authors.lastname: Granel
authors.forename: P
authors.initials: P
authors.lastname: Disdier
authors.forename: P J
authors.initials: PJ
authors.lastname: Weiller
authors.forename: M
authors.initials: M
authors.lastname: Galliano
mesh_terms: D000225:Adenine; D000595:Amino Acid Sequence; D018388:Codon, Terminator; D003488:Cyanogen Bromide; D004220:Disulfides / Q000737:chemistry; D005091:Exons; D016368:Frameshift Mutation; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D007585:Jews; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009018:Morocco; D009844:Oligosaccharides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D012709:Serum Albumin / Q000737:chemistry* / Q000235:genetics*; D000075462:Serum Albumin, Human
chemical_list: C422455:ALB protein, human; D018388:Codon, Terminator; D004220:Disulfides; D006023:Glycoproteins; D009844:Oligosaccharides; D010446:Peptide Fragments; D012709:Serum Albumin; D000225:Adenine; D003488:Cyanogen Bromide; D000075462:Serum Albumin, Human