ID:RMP_HUMAN DESCRIPTION: RecName: Full=Unconventional prefoldin RPB5 interactor 1; AltName: Full=Protein NNX3; AltName: Full=Protein phosphatase 1 regulatory subunit 19; AltName: Full=RNA polymerase II subunit 5-mediating protein; Short=RPB5-mediating protein; FUNCTION: Involved in gene transcription regulation. Acts as a transcriptional repressor in concert with the corepressor UXT to regulate androgen receptor (AR) transcription. May act as a tumor suppressor to repress AR-mediated gene transcription and to inhibit anchorage-independent growth in prostate cancer cells. Required for cell survival in ovarian cancer cells. Together with UXT, associates with chromatin to the NKX3-1 promoter region. Antagonizes transcriptional modulation via hepatitis B virus X protein. FUNCTION: Plays a central role in maintaining S6K1 signaling and BAD phosphorylation under normal growth conditions thereby protecting cells from potential deleterious effects of sustained S6K1 signaling. The URI1-PPP1CC complex acts as a central component of a negative feedback mechanism that counteracts excessive S6K1 survival signaling to BAD in response to growth factors. Mediates inhibition of PPP1CC phosphatase activity at mitochondria. Coordinates the regulation of nutrient-sensitive gene expression availability in a mTOR-dependent manner. Seems to be a scaffolding protein able to assemble a prefoldin-like complex that contains PFDs and proteins with roles in transcription and ubiquitination. SUBUNIT: Homodimer. Component of the URI complex that contains PFDN2, POLR2E/RPB5, RUVBL2, RUVBL1 and URI1. Interacts with PPP1CC; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts with PFDN2, PFDN4 and STAP1; the interactions are phosphorylation-dependent and occurs in a growth-dependent manner in the mitochondrion. Interacts (via the middle C-terminus region) with GTF2F1 and GTF2F2. Interacts with DMAP1, POLR2E/RPB5 and UXT. INTERACTION: P35269:GTF2F1; NbExp=3; IntAct=EBI-357067, EBI-457886; P13984:GTF2F2; NbExp=4; IntAct=EBI-357067, EBI-1030560; P19388:POLR2E; NbExp=2; IntAct=EBI-357067, EBI-395189; P36873:PPP1CC; NbExp=5; IntAct=EBI-357067, EBI-356283; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion. Cell projection, dendrite (By similarity). Note=Colocalizes with PFDN2, PFDN4, PPP1CC, RPS6KB1 and STAP1 at mitochondrion. TISSUE SPECIFICITY: Ubiquitous. Expressed in ovarian cancers (at protein level). Expressed strongly in skeletal muscle. Expressed weakly in brain, heart, pancreas and in prostate epithelial cells. PTM: Phosphorylated. Phosphorylation occurs essentially on serine residues. Phosphorylation occurs in response to androgen treatment in prostate cancer cells in a mTOR-dependent manner. Phosphorylated; hyperhosphorylated in mitochondria in a mTORC- dependent signaling pathway. Phosphorylated at Ser-372 by RPS6KB1 in a growth factor- and rapamycin-dependent manner. S6K1-mediated mitochondrial phosphorylation at Ser-372 disrupts the URI1-PPP1CC complex in the mitochondrion, releaves PPP1CC phosphatase inhibition activity and hence engages a negative feedback diminishing RPS6KB1 kinase activity and preventing sustained S6K1- dependent signaling. SIMILARITY: Belongs to the RNA polymerase II subunit 5-mediating protein family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF02996 - Prefoldin subunit PF12927 - Domain of unknown function (DUF3835) PF13758 - Prefoldin subunit
SCOP Domains: 48371 - ARM repeat 46579 - Prefoldin
ModBase Predicted Comparative 3D Structure on O94763
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.