IDENTIFICATION AND CHARACTERIZATION OF A NEW HUMAN GENE (APOC4) IN THE APOLIPOPROTEIN-E, C-I, AND C-II GENE LOCUS

We have identified and characterized a previously unreported human gen e that is found within the apolipoprotein (apo) E/C-I/C-II gene locus. On the basis of its location and its properties, this new gene has be en designated APOC4, Nucleotide sequence analysis of genomic DNA and l iver cDNA clones revealed a 3.3-kb gene consisting of three exons and two introns. Its 3' terminus lies 555 bp upstream of APOC2, giving bot h genes the same transcriptional orientation. The promoter of the APOC 4 gene lacks a typical TATA box, consistent with an apparent heterogen eity in transcription start sites. RNase protection analysis indicated relatively low apoC-IV mRNA levels in human liver, compared to apoC-I I mRNA levels. The predicted apoC-IV protein sequence, comprising 127 amino acid residues, contains a putative 25-residue signal peptide and two potential amphipathic alpha-helical domains. Amino acid sequence comparisons indicate a limited homology between apoC-IV and either apo C-I or apoC-II. Since its hepatic expression and predicted protein str ucture are characteristic of the other genes in this cluster, we propo se that the APOC4 gene is a member of the apolipoprotein gene family. (C) 1995 Academic Press, Inc.