title: FOR, a novel orphan nuclear receptor related to farnesoid X receptor.
abstract: We have identified and characterized a new amphibian orphan member of the nuclear receptor superfamily and termed it FOR1 (farnesoid X receptor (FXR)-like Orphan Receptor) because it shares the highest amino acid identity with the mammalian FXR. We also identified a variant of FOR1, called FOR2, which has 15 additional C-terminal amino acids. Both variants include an unusual insertion of 33 amino acids in the helix 7 region of the canonical ligand binding domain sequence, suggesting a unique structure for FOR. Northern blot analysis demonstrates that the FOR gene is highly expressed in adult and tadpole liver, kidney, and tail bud stage of the embryo. Detailed expression analysis using in situ hybridization indicates that FOR expression is first detectable at stage 30/31 in the presumptive liver region lasting until stage 41 with a peak level evident at stage 35/36. FOR forms heterodimeric complexes with retinoid X receptor (RXR) as demonstrated by biochemical and mammalian two-hybrid approaches. Gel mobility shift assays demonstrate that FORs form specific DNA-protein complexes on an FXR binding element consisting of an inverted repeat DNA element with 1 nucleotide spacing (IR1) from the phospholipid transfer protein gene promoter. Finally, although FORs do not exhibit constitutive transcriptional activity, frog gallbladder extract significantly augments the transcriptional activities of FORs.
authors.affiliation: Hormone Research Center, Department of Biology, Chonnam National University, Kwangju 500-757, Republic of Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Seo
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Sanyal
authors.forename: Han-Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Won
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: An
authors.forename: Tosikazu
authors.initials: T
authors.lastname: Amano
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Zavacki
authors.forename: Hyuk-Bang
authors.initials: HB
authors.lastname: Kwon
authors.forename: Yun-Bo
authors.initials: YB
authors.lastname: Shi
authors.forename: Won-Sun
authors.initials: WS
authors.lastname: Kim
authors.forename: Heonjoong
authors.initials: H
authors.lastname: Kang
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
authors.forename: Hueng-Sik
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002025:Bufonidae; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005704:Gallbladder / Q000737:chemistry; D017403:In Situ Hybridization; D008024:Ligands; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000302:isolation & purification*; D018168:Receptors, Retinoic Acid / Q000737:chemistry; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000254:growth & development; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D029867:Xenopus Proteins; D000099150:Receptor, Farnesoid X-Activated; C459605:farnesoid X receptor-like orphan receptor, Xenopus