RMP (RPB5-mediating protein), also known as C19orf2, NNX3 or URI, is a 534 amino acid protein that localizes to the nucleus and belongs to the RNA polymerase II subunit 5-mediating protein family. Expressed ubiquitously, RMP functions as a component of the multi-protein URI complex and is thought to play a role in protein scaffolding that may be involved in transcription and ubiquitination. Multiple isoforms of RMP exist due to alternative splicing events. The gene encoding RMP maps to human chromosome 19, which consists of over 63 million bases, houses approximately 1,400 genes and is recognized for having the greatest gene density of the human chromosomes.
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.
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 sigaling 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.
Subcellular Location:
Nucleus. Cytoplasm. Mitochondrion. Cell projection > dendrite. 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.
Post-translational modifications:
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 mTORSLCdependent 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.
SWISS:
O94763
Gene ID:
8725
Database links:
Entrez Gene: 8725 Human
Omim: 603494 Human
SwissProt: O94763 Human
Unigene: 466391 Human
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