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Biochemistry
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
Edited by Ronald W. Estabrook, University of Texas Southwestern
Medical Center, Dallas, TX, and approved December 17, 2002 (received for review October 9, 2002)
Recently we discovered a previously uncharacterized gene
with the characteristics of a membrane progestin receptor (mPR) ina
fish model, spotted seatrout. Here, we report the identification,cloning, and characteristics of other members of this hithertounknown
family of putative mPRs from several vertebrate species,including
human, mouse, pig, Xenopus, zebrafish, and
Fugu, withhighly conserved nucleotide and deduced amino
acid sequences andsimilar structures to the spotted seatrout mPR. The
13 vertebrategenes identified seem to belong to an unknown gene
family. Phylogeneticanalysis indicates these cDNAs comprise three
distinct groups(named , , and ) within this gene family.
Structural analysesof the translated cDNAs suggest they encode
membrane proteinswith seven transmembrane domains. The transcript
sizes of thehuman , , and putative mPR mRNAs varied from 2.8 to 5.8 kband showed distinct distributions in reproductive, neural,
kidneyand intestinal tissues, respectively. Recombinant human
, ,and mouse proteins produced in an Escherichia
coli expressionsystem demonstrated high affinity
(Kd = 20-30 nM) saturable bindingfor
progesterone. Further analysis of binding to the -subtyperevealed 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
receptorsunrelated to nuclear steroid receptors, but instead having
characteristicsof G protein-coupledreceptors.
§
To whom correspondence should be addressed. E-mail:
thomas{at}utmsi.utexas.edu.
www.pnas.org/cgi/doi/10.1073/pnas.0436133100
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,
,
, 
, and 
) 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 
