Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product

J Biol Chem. 1997 Oct 31;272(44):28081-8. doi: 10.1074/jbc.272.44.28081.


Mouse Spa-1 gene with a region homologous to the human rap1GAP gene is transcriptionally induced in the lymphocytes by mitogenic stimulation. Herein we have cloned a cDNA for its human counterpart. SPA-1 cDNA encodes a 130-kDa protein (p130(SPA-1)) consisting of proline-rich regions and rap1GAP-related domain followed by a coiled-coil stretch. Baculovirally expressed p130(SPA-1) exhibited GTPase-activating protein (GAP) activity for Rap1 and Rap2, but not for Ras, Rho, Cdc42, Rac, and Ran, with comparable specific activity to the rap1GAP gene product (p85/95(rap1GAP)). In the cells, p130(SPA-1) was mostly localized at the perinuclear membranous region co-localizing with Rap1 and Rap2. Expression of SPA-1 and rap1GAP genes tended to be segregate in various tissues, lymphoid tissues expressing abundant SPA-1 transcript without rap1GAP, while those such as brain, kidney, and pancreas exhibiting rap1GAP mRNA with little SPA-1. Promyelocytic HL-60 cells, which expressed p130(SPA-1) with little p85/95(rap1GAP) in uninduced state, showed progressive decline in p130(SPA-1) and conversely drastic increase in p85/95(rap1GAP) as they ceased from proliferation and differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate. These results suggested that products of SPA-1 and rap1GAP genes, albeit comparable GAP activity for Rap1 and Rap2, functioned in the distinct contexts depending on cell types and/or states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • DNA, Complementary
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Humans
  • Lymphoid Tissue / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Proteins / genetics*
  • Proteins / metabolism
  • rap GTP-Binding Proteins
  • ras GTPase-Activating Proteins


  • DNA, Complementary
  • GTPase-Activating Proteins
  • Nuclear Proteins
  • Proteins
  • SIPA1 protein, human
  • ras GTPase-Activating Proteins
  • GTP-Binding Proteins
  • rap GTP-Binding Proteins

Associated data

  • GENBANK/AB005666
  • GENBANK/D11374