Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain.
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.
Mifsud
William
W
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
Bateman
Alex
A
D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002417:Cattle; D015786:Cytochromes b5 / Q000737:chemistry / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D017434:Protein Structure, Tertiary / Q000235:genetics; D011980:Receptors, Progesterone / Q000737:chemistry* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases
D029742:Caenorhabditis elegans Proteins; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; C486527:Herc2 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D011980:Receptors, Progesterone; D015786:Cytochromes b5; C118566:HERC2 protein, human; D044767:Ubiquitin-Protein Ligases