Cloning and characterization of an atypical Type IV P-type ATPase that binds to the RING motif of RUSH transcription factors.
RUSH proteins are SWI/SNF-related transcription factors with RING finger signatures near their COOH termini. Long suspected of mediating protein-protein interactions, the RING motif was used to clone a binding partner. The RING finger binding protein (RFBP) is a Type IV P-type ATPase, a putative phospholipid pump, with conserved sequences for two loop segments, an ATP-binding site, a phosphorylation domain, and transmembrane passes potentially involved in substrate binding and translocation. However, RFBP differs from all other Type IV P-type ATPases in three ways. It has only three of four highly conserved NH(2)-terminal transmembrane passes, it is located in the inner nuclear membrane, and it binds the RING domain. Topographically the orientation of the adjacent hydrophilic domains and the determinants of transport specificity are altered. As a result, the small, hydrophilic loop extends into the perinuclear space that is contiguous with the lumen of the endoplasmic reticulum. The large, conformationally flexible loop extends into the nucleoplasm to contact euchromatin. Competitive reverse transcriptase-polymerase chain reaction and high performance liquid chromatography analysis revealed that endometrial RFBP mRNA expression is hormonally regulated. The physical association of a hormone-dependent RING finger-binding protein with transcriptionally active chromatin supports the speculation that RFBP plays a role in the subnuclear trafficking of transcription factors with RING motifs.
Mansharamani
M
M
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Hewetson
A
A
Chilton
B S
BS
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016678:Genome; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011817:Rabbits; D014157:Transcription Factors
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; C104270:SMARCA3 protein, Oryctolagus cuniculus; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C420204:RING-finger binding protein, Oryctolagus cuniculus