Structure, evolution, and tissue-specific synthesis of human apolipoprotein AIV.
Apolipoprotein AIV (apoAIV) is a protein of the lipid transport system found associated with chylomicrons, high-density lipoprotein (HDL), and the lipoprotein-free fraction of the plasma. The gene coding for the human apoAIV is closely linked with the genes coding for apolipoproteins AI (apoAI) and CIII (apoCIII). In this paper a nearly full-length apoAIV cDNA clone has been isolated by screening an adult human liver DNA library using a human apoAIV gene probe. In-frame translation of the cDNA sequence in this clone indicated that the human apoAIV consists of 396 amino acid residues including a 20 residue long signal peptide. The coding region of this cDNA sequence contains 15 nucleotide repeats, 11 of which code for amino acid repeats with potentials of forming amphipathic helices. Alignment and comparison of the human and rat apoAIV amino acid sequences indicated a five-residue deletion near the carboxy terminus of the rat protein. This comparison also indicated that these proteins are 61.8% homologous, suggesting that the rate of evolution of apoAIV is 65 accepted point mutations (PAMs) per 100 residues per 100 million years. The rates of evolution of certain amino acid repeats in apoAIV are higher than the rate of evolution of the entire protein. However, the corresponding, computer-generated, secondary structures and hydropathy profiles of these repeats are very similar between the human and rat apoAIV. The relative steady-state levels of apoAIV mRNA in various human and monkey tissues were determined by hybridization blotting analysis of total RNA from these tissues using a human apoAIV cDNA probe.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001054:Apolipoproteins A / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D005260:Female; D005333:Fetus; D005796:Genes; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013045:Species Specificity
D001054:Apolipoproteins A; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D004247:DNA