Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site

Proc Natl Acad Sci U S A. 1990 Jan;87(1):26-30. doi: 10.1073/pnas.87.1.26.

Abstract

Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63Ni2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation (since proalbumin contains adjacent Arg residues at -1 and -2) or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala----Thr. This introduces an Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg----Cys. This introduces a prepro sequence, Met-Lys-Trp-Val-Thr-Phe-Ile-Ser-Leu-Leu-Phe-Leu-Phe-Ser-Ser-Ala-Tyr- Ser-Arg-Gly-Val-Phe-Cys-Arg (cf.-Tyr-Ser-Arg-Gly-Val-Phe-Arg-Arg- in normal human pre-proalbumin). We propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine*
  • Amino Acid Sequence
  • Arginine*
  • Base Sequence
  • Endopeptidases / metabolism*
  • Genes
  • Genetic Variation*
  • Humans
  • Membrane Proteins*
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Peptide Fragments / isolation & purification
  • Peptide Mapping
  • Polymerase Chain Reaction
  • Prealbumin / genetics*
  • Sequence Homology, Nucleic Acid
  • Serine Endopeptidases*
  • Serum Albumin / genetics*
  • Serum Albumin, Human
  • Threonine*
  • Trypsin

Substances

  • Membrane Proteins
  • Oligonucleotide Probes
  • Peptide Fragments
  • Prealbumin
  • Serum Albumin
  • albumin Redhill
  • Threonine
  • Arginine
  • Endopeptidases
  • Serine Endopeptidases
  • Trypsin
  • type I signal peptidase
  • Alanine
  • Serum Albumin, Human