Human apoC-IV: isolation, characterization, and immunochemical quantification in plasma and plasma lipoproteins

J Lipid Res. 2003 Jul;44(7):1387-94. doi: 10.1194/jlr.M300087-JLR200. Epub 2003 Apr 16.


Apolipoprotein C-IV (apoC-IV), the newest member of the low-molecular-weight apoC group, has been characterized in blood plasma of rabbits, in which it is a major proline-rich apoC component (Zhang, L-H., L. Kotite, and R. J. Havel. 1996. Identification, characterization, cloning, and expression of apoC-IV, a novel sialoglycoprotein of rabbit plasma lipoproteins. J. Biol. Chem. 271: 1776-1783). Although the decoded sequence of mouse and human apoC-IV is known, apoC-IV has not been identified in blood plasma from these or other species. Rabbit apoC-IV exists in several sialoforms, and the asialoform has an acidic isoelectric point. We show that apoC-IV is a basic protein in human, monkey, and mouse plasma, present as a minor apoC component of VLDL. Human apoC-IV, isolated from apo VLDL by DEAE-cellulose chromatography and two-dimensional electrophoresis, was identified by microsequencing four tryptic peptides. The protein exhibits two major isoforms; one is N-glycosylated, and both are variably sialylated. In normolipidemic plasma, greater than 80% of the protein is in VLDL (0.7% of total apo VLDL), with most of the remainder in HDL. The concentration of apoC-IV in the plasma and lipoproteins of rho < 1.21 g/ml is closely related to plasma triglyceride concentration up to 1,770 mg/dl, varying from 0.1-1.9 mg/dl. Neither the human nor rabbit apoC-IV gene contains a typical TATA box in the 5'-flanking region, but the 5'-untranslated region of the rabbit gene contains a unique purine-rich sequence, GGGACAG(G/A), repeated nine times in tandem, with an additional two within the 5'-flanking sequence. This sequence, functioning as a GAGA box that has been implicated in the transcription of a number of genes, may explain the higher level of expression of apoC-IV in rabbits.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions
  • Amino Acid Sequence
  • Animals
  • Apolipoproteins C / blood
  • Apolipoproteins C / chemistry*
  • Apolipoproteins C / isolation & purification*
  • Base Sequence
  • Cellulose / chemistry
  • Chromatography
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Glycosylation
  • Haplorhini
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Lipoproteins / chemistry
  • Mass Spectrometry
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Peptides / chemistry
  • Protein Isoforms
  • Rabbits
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic
  • Trypsin / chemistry
  • Ultracentrifugation


  • 5' Untranslated Regions
  • APOC4 protein, human
  • Apoc4 protein, mouse
  • Apolipoproteins C
  • Lipoproteins
  • Peptides
  • Protein Isoforms
  • Cellulose
  • Trypsin