Phosphorylation of human plasma alpha2-Heremans-Schmid glycoprotein (human fetuin) in vivo

Biochem J. 2001 Jul 15;357(Pt 2):437-45. doi: 10.1042/0264-6021:3570437.


A fraction of alpha2-Heremans-Schmid (alpha2-HS) glycoprotein (human fetuin) isolated from plasma was phosphorylated at serine-120 and serine-312 as shown by MS and peptide fragment sequencing after tryptic digestion. Serine-312-containing peptides were phosphorylated to 77% as determined from relative peak heights in the mass spectrum, which together with the phosphorylation of serine-120 implies a molar degree of phosphorylation of at least 1. Approximately 20% of the circulating fetuin plasma pool was phosphorylated to approx. 1 mol of phosphate/mol of protein. The remainder did not contain phosphate, resulting in an average phosphorylation degree for the protein in plasma of approx. 0.2 mol/mol. The isolated alpha2-HS glycoprotein was a heterodimer in which the entire C-terminal part of the connecting peptide including threonine-321 was present, but traces of C-terminally trimmed connecting peptide fragments were also found. The short B-chain was O-glycosylated to approx. 40%, whereas the N-glycosylation of asparagine-138 and asparagine-158 seemed to be 100%. This finding, for the first time, that circulating human plasma fetuin is partly phosphorylated, implies that the effects of phosphorylated alpha2-HS glycoprotein on insulin signal transduction seen in different cell systems could be relevant to its physiological function in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Blood Proteins / chemistry*
  • Blood Proteins / isolation & purification
  • Chromatography, Affinity
  • Chromatography, Ion Exchange
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Phosphopeptides / chemistry
  • Phosphopeptides / isolation & purification
  • Phosphorylation
  • Phosphoserine / analysis
  • Pregnancy
  • Pregnancy Trimester, Third
  • Protein Processing, Post-Translational
  • alpha-2-HS-Glycoprotein
  • alpha-Fetoproteins / chemistry*
  • alpha-Fetoproteins / isolation & purification


  • AHSG protein, human
  • Blood Proteins
  • Peptide Fragments
  • Phosphopeptides
  • alpha-2-HS-Glycoprotein
  • alpha-Fetoproteins
  • Phosphoserine