nuclear receptor-interacting protein 1; nuclear factor RIP140; receptor-interacting protein 140 (NRIP1)

Function: - modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 & ESR1 - also modulates transcriptional repression by nuclear hormone receptors - interacts with the ligand binding domain (LBD) of NR2C1 in the absence of ligand - interacts with RARA & RXRB homodimers & RARA/RXRB heterodimers in the presence of ligand - interacts with HDAC1 & HDAC3 via its N-terminal domain (putative) - interacts with CTBP1, CTBP2, ESR1, HDAC1, HDAC2, HDAC5, HDAC6, NR3C1, NR3C2, YWHAH, JUN & FOS - found in a complex with both NR3C1 & YWHAH - acetylation regulates its nuclear translocation & corepressive activity (putative) - acetylation abolishes interaction with CTBP1 - phosphorylation enhances interaction with YWHAH Structure: - 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 & RXRB homo- & heterodimers, for the corepressor activity, & for the formation of an HDAC3 complex with RARA/RXRB (putative) - contains at least four autonomous repression domains (RD1-4) a) RD1 functions via a histone deacetylase (HDAC)-independent mechanism b) RD2, RD3 & RD4 can function by HDAC-dependent or independent mechanisms, depending on cell type c) RD2 is dependent on CTBP binding Compartment: - nucleus - localized to discrete foci - redistributes to larger nuclear domains upon binding to ligand-bound NR3C1 Pathology: - genetic variation in NRIP1 may act as predisposing factor for endometriosis

General

nuclear protein phosphoprotein

Properties

SIZE: entity length = 1158 aa MW = 127 kD COMPARTMENT: cell nucleus MOTIF: LXXLL motif 1 {21-25} repression domain 1 {78-333} MOTIF: Ser phosphorylation site {S104} LXXLL motif 2 {133-137} LXXLL motif 3 {185-189} Thr phosphorylation site {T207} LXXLL motif 4 {266-270} Ser phosphorylation site {S356} Ser phosphorylation site {S378} LXXLL motif 5 {380-384} repression domain 2 {410-700} MOTIF: nuclear targeting {431-472} CTBP-binding; principal site {440-446} Ser phosphorylation site {S487} LXXLL motif 6 {500-504} Ser phosphorylation site {S518} Ser phosphorylation site {S542} CTBP-binding {565-569} CTBP-binding {599-603} Ser phosphorylation site {S671} LXXLL motif 7 {713-717} Thr phosphorylation site {T731} repression domain 3 {735-885} MOTIF: LXXLL motif 8 {819-823} LXXLL motif 9 {936-940} CTBP-binding {946-950} Ser phosphorylation site {S1001} ligand-dependent nuclear receptor binding {1061-1074} repression domain 4 {1118-1158}

Database Correlations

OMIM 602490 UniProt P48552 Kegg hsa:8204

References

UniProt :accession P48552