Nuclear receptor-interacting protein 1
Domain
Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have different affinities for nuclear receptors. The C-terminal LTKTNPILYYMLQK motif is required for ligand-dependent interaction with RAAR and RXRB homodimers and heterodimers, for the corepressor activity, and for the formation of an HDAC3 complex with RARA/RXRB (By similarity). Contains at least four autonomous repression domains (RD1-4). RD1 functions via a histone deacetylase (HDAC)-independent mechanism, whereas RD2, RD3 and RD4 can function by HDAC-dependent or independent mechanisms, depending on cell type. RD2 is dependent on CTBP binding.
Function
Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors. Positive regulator of the circadian clock gene expression: stimulates transcription of BMAL1, CLOCK and CRY1 by acting as a coactivator for RORA and RORC. Involved in the regulation of ovarian function (By similarity). Plays a role in renal development (PubMed:28381549).
Involvement in disease
Congenital anomalies of kidney and urinary tract 3
CAKUT3
A disorder encompassing a broad spectrum of renal and urinary tract malformations that include renal agenesis, kidney hypodysplasia, multicystic kidney dysplasia, duplex collecting system, posterior urethral valves and ureter abnormalities. Congenital anomalies of kidney and urinary tract are the commonest cause of chronic kidney disease in children. CAKUT3 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Acetylation regulates its nuclear translocation and corepressive activity (By similarity). Acetylation abolishes interaction with CTBP1. Phosphorylation enhances interaction with YWHAH.
Cellular localization
- Nucleus
- Localized to discrete foci and redistributes to larger nuclear domains upon binding to ligand-bound NR3C1.
Alternative names
Nuclear receptor-interacting protein 1, Nuclear factor RIP140, Receptor-interacting protein 140, NRIP1