Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor
- Yong Zhu†,‡,
- Jason Bond‡, and
- Peter Thomas†,§
- †Marine Science Institute, University of Texas at Austin, 750 Channel View Drive, Port Aransas, TX 78373; and ‡Department of Biology, East Carolina University, 1000 East Fifth Street, Greenville, NC 27858
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Edited by Ronald W. Estabrook, University of Texas Southwestern Medical Center, Dallas, TX, and approved December 17, 2002 (received for review October 9, 2002)
Abstract
Recently we discovered a previously uncharacterized gene with the characteristics of a membrane progestin receptor (mPR) in a fish model, spotted seatrout. Here, we report the identification, cloning, and characteristics of other members of this hitherto unknown family of putative mPRs from several vertebrate species, including human, mouse, pig, Xenopus, zebrafish, and Fugu, with highly conserved nucleotide and deduced amino acid sequences and similar structures to the spotted seatrout mPR. The 13 vertebrate genes identified seem to belong to an unknown gene family. Phylogenetic analysis indicates these cDNAs comprise three distinct groups (named α, β, and γ) within this gene family. Structural analyses of the translated cDNAs suggest they encode membrane proteins with seven transmembrane domains. The transcript sizes of the human α, β, and γ putative mPR mRNAs varied from 2.8 to 5.8 kb and showed distinct distributions in reproductive, neural, kidney and intestinal tissues, respectively. Recombinant human α, γ, and mouse β proteins produced in an Escherichia coli expression system demonstrated high affinity (K d = 20–30 nM) saturable binding for progesterone. Further analysis of binding to the γ-subtype revealed binding was specific for progestins and was displaceable, with rapid rates of association and dissociation (t1/2 = 2–8 min). These results suggest this is a new family of steroid receptors unrelated to nuclear steroid receptors, but instead having characteristics of G protein-coupled receptors.
Footnotes
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↵ § To whom correspondence should be addressed. E-mail: thomas{at}utmsi.utexas.edu.
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This paper was submitted directly (Track II) to the PNAS office.
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Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF315615–AF315620 and AY149119–AY1419121).
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See commentary on page 2168.
- Abbreviations:
- mPR,
- membrane progestin receptor;
- GPCR,
- G protein-coupled receptor
- Copyright © 2003, The National Academy of Sciences
