Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain

Genome Biol. 2002;3(12):RESEARCH0068. doi: 10.1186/gb-2002-3-12-research0068. Epub 2002 Nov 12.


Background: Membrane-associated progesterone receptors (MAPRs) are thought to mediate a number of rapid cellular effects not involving changes in gene expression. They do not show sequence similarity to any of the classical steroid receptors. We were interested in identifying distant homologs of MAPR better to understand their biological roles.

Results: We have identified MAPRs as distant homologs of cytochrome b5. We have also found regions homologous to cytochrome b5 in the mammalian HERC2 ubiquitin transferase proteins and a number of fungal chitin synthases.

Conclusions: In view of these findings, we propose that the heme-binding cytochrome b5 domain served as a template for the evolution of membrane-associated binding pockets for non-heme ligands.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins / genetics
  • Cattle
  • Cytochromes b5 / chemistry
  • Cytochromes b5 / genetics*
  • Fungal Proteins / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Ligands
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics*
  • Mice
  • Protein Structure, Tertiary / genetics
  • Receptors, Progesterone / chemistry*
  • Receptors, Progesterone / genetics*
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligases


  • Caenorhabditis elegans Proteins
  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Herc2 protein, mouse
  • Ligands
  • Membrane Proteins
  • Receptors, Progesterone
  • Cytochromes b5
  • HERC2 protein, human
  • Ubiquitin-Protein Ligases