The human Cas1 protein: a sialic acid-specific O-acetyltransferase?

Glycobiology. 2011 May;21(5):553-64. doi: 10.1093/glycob/cwq153. Epub 2010 Oct 14.


Sialic acids are important sugars at the reducing end of glycoproteins and glycolipids. They are among many other functions involved in cell-cell interactions, host-pathogen recognition and the regulation of serum half-life of glycoproteins. An important modification of sialic acids is O-acetylation, which can alter or mask the biological properties of the parent sialic acid molecule. The nature of mammalian sialate-O-acetyltransferases (EC involved in their biosynthesis is still unknown. We have identified the human CasD1 (capsule structure1 domain containing 1) gene as a candidate to encode the elusive enzyme. The human CasD1 gene encodes a protein with a serine-glycine-asparagine-histidine hydrolase domain and a hydrophobic transmembrane domain. Expression of the Cas1 protein tagged with enhanced green fluorescent protein in mammalian and insect cells directed the protein to the medial and trans-cisternae of the Golgi. Overexpression of the Cas1 protein in combination with α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (GD3 synthase) resulted in an up to 40% increased biosynthesis of 7-O-acetylated ganglioside GD3. By quantitative real-time polymerase chain reaction, we found up to 5-fold increase in CasD1 mRNA in tumor cells overexpressing O-Ac-GD3. CasD1-specific small interfering RNA reduced O-acetylation in tumor cells. These results suggest that the human Cas1 protein is directly involved in O-acetylation of α2-8-linked sialic acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / genetics*
  • Acetyltransferases / metabolism
  • Amino Acid Sequence
  • Carbohydrate Epimerases / metabolism*
  • Catalytic Domain
  • Cell Line
  • Cloning, Molecular
  • Data Mining
  • Gene Knockdown Techniques
  • Humans
  • Lymphocytes / metabolism
  • Molecular Sequence Data
  • N-Acetylneuraminic Acid / metabolism*
  • Protein Structure, Tertiary
  • RNA Interference
  • Sequence Alignment
  • Substrate Specificity
  • Up-Regulation


  • Acetyltransferases
  • CasD1 protein, human
  • Carbohydrate Epimerases
  • dermatan sulfate epimerase 1, mouse
  • N-Acetylneuraminic Acid