Genomic Organization of Human and Mouse Genes for Vascular Endothelial Growth Factor C

J Biol Chem. 1997 Oct 3;272(40):25176-83. doi: 10.1074/jbc.272.40.25176.

Abstract

We report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) family. Both VEGF-C genes comprise over 40 kilobase pairs of genomic DNA and consist of seven exons, all containing coding sequences. The VEGF homology domain of VEGF-C is encoded by exons 3 and 4. Exons 5 and 7 encode cysteine-rich motifs of the type C6C10CRC, and exon 6 encodes additional C10CXCXC motifs typical of a silk protein. A putative alternatively spliced rare RNA form lacking exon 4 was identified in human fibrosarcoma cells, and a major transcription start site was located in the human VEGF-C gene 523 base pairs upstream of the translation initiation codon. The upstream promoter sequences contain conserved putative binding sites for Sp-1, AP-2, and NF-kappaB transcription factors but no TATA box, and they show promoter activity when transfected into cells. The VEGF-C gene structure is thus assembled from exons encoding propeptides and distinct cysteine-rich domains in addition to the VEGF homology domain, and it shows both similarities and distinct differences in comparison with other members of the VEGF/PDGF gene family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • Cysteine
  • DNA Primers
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics*
  • Exons
  • Fibrosarcoma
  • Genetic Variation
  • Genomic Library
  • Humans
  • Introns
  • Mice
  • Molecular Sequence Data
  • Multigene Family
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Restriction Mapping
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor C

Substances

  • DNA Primers
  • Endothelial Growth Factors
  • Transcription Factors
  • Vascular Endothelial Growth Factor C
  • Cysteine