Genomic organization of the human adipocyte-derived leucine aminopeptidase gene and its relationship to the placental leucine aminopeptidase/oxytocinase gene

J Biochem. 2001 Aug;130(2):235-41. doi: 10.1093/oxfordjournals.jbchem.a002977.

Abstract

The genomic organization of the gene encoding the human adipocyte-derived leucine aminopeptidase (A-LAP) has been determined. The gene is composed of 20 exons and 19 introns and spans approximately 47 kilobases of chromosome 5q15. The gluzincin aminopeptidase motif, the HEXXH(X)(18)E zinc-binding motif essential for enzymatic activity, is encoded by exons 6 and 7. A comparison of the exon/intron boundaries, together with phylogenetic analysis, shows the close relationship between A-LAP and placental leucine aminopeptidase (P-LAP)/oxytocinase, another gluzincin aminopeptidase considered to be important for the maintenance of normal pregnancy. Primer extension analysis revealed two transcriptional initiation sites. Analysis of the sequence immediately upstream of the transcriptional initiation sites revealed that the A-LAP promoter contains no canonical TATA- or CCAAT-box, but has a PyPyA(+1)N(T/A)PyPy initiator consensus sequence and multiple putative regulatory elements. Finally, luciferase-reporter assays revealed a functional promoter activity of the 5'-flanking region of the gene, and suggested that the activity is regulated in a cell type-specific manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / enzymology
  • Adipocytes / physiology*
  • Base Sequence
  • Cystinyl Aminopeptidase / genetics*
  • Gene Expression Regulation
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Leucyl Aminopeptidase / classification
  • Leucyl Aminopeptidase / genetics*
  • Molecular Sequence Data
  • Phylogeny
  • Promoter Regions, Genetic*
  • Recombinant Fusion Proteins / metabolism

Substances

  • Recombinant Fusion Proteins
  • Leucyl Aminopeptidase
  • Cystinyl Aminopeptidase
  • leucyl-cystinyl aminopeptidase