CZH proteins: a new family of Rho-GEFs

J Cell Sci. 2005 Nov 1;118(Pt 21):4937-46. doi: 10.1242/jcs.02671.


The Rho family of small GTPases are important regulators of multiple cellular activities and, most notably, reorganization of the actin cytoskeleton. Dbl-homology (DH)-domain-containing proteins are the classical guanine nucleotide exchange factors (GEFs) responsible for activation of Rho GTPases. However, members of a newly discovered family can also act as Rho-GEFs. These CZH proteins include: CDM (Ced-5, Dock180 and Myoblast city) proteins, which activate Rac; and zizimin proteins, which activate Cdc42. The family contains 11 mammalian proteins and has members in many other eukaryotes. The GEF activity is carried out by a novel, DH-unrelated domain named the DOCKER, CZH2 or DHR2 domain. CZH proteins have been implicated in cell migration, phagocytosis of apoptotic cells, T-cell activation and neurite outgrowth, and probably arose relatively early in eukaryotic evolution.

Publication types

  • Review

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / metabolism
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Multigene Family*
  • Plant Proteins / chemistry
  • Plant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • rac GTP-Binding Proteins / chemistry*
  • rac GTP-Binding Proteins / metabolism


  • CED-5 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • DOCK1 protein, human
  • DOCK9 protein, human
  • Drosophila Proteins
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • Plant Proteins
  • Saccharomyces cerevisiae Proteins
  • mbc protein, Drosophila
  • rac GTP-Binding Proteins