nischarin; imidazoline receptor 1; IR1; I-1; imidazoline-1 receptor; I1R; imidazoline receptor antisera-selected protein; hIRAS; imidazoline-1 receptor candidate protein; I-1 receptor candidate protein; I1R candidate protein (NISCH, IRAS, KIAA0975)

Function: - functional imidazoline-1 receptor, mediates signaling - binds numerous imidazoline ligands - induces initiation of cell-signaling cascades triggering cell survival, growth & migration - activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 & MAPK3 in rostral ventrolateral medulla neurons that exhibit rilmenidine-evoked hypotension; blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation - modulator of Rac-regulated signal transduction pathways - suppresses Rac1-stimulated cell migration by interacting with PAK1 & inhibiting its kinase activity - blocks Pak-independent Rac signaling by interacting with RAC1 & inhibiting Rac1-stimulated NF-kB response element & cyclin D1 promoter activation - inhibits also LIMK1 kinase activity by reducing LIMK1 Tyr-508 phosphorylation (putative) - inhibits Rac-induced cell migration & invasion in breast & colon epithelial cells (putative) - inhibits lamellipodia formation, when overexpressed (putative) - plays a role in protection against apoptosis - involved in association with IRS4 in the enhancement of insulin activation of MAPK1 & MAPK3 - when overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures - interacts with GRB2 - interacts with PIK3R1 - probably associates with the PI3-kinase complex - interacts with IRS4 - found in a complex with ITGA5 & PAK1. - found in a complex with LIMK1 & PAK1 - interacts with ITGA5 (via cytoplasmic domain); interaction is direct. - interacts with PAK1 (via kinase domain); th interaction is direct & is increased upon activation of PAK1 (putative) - interacts with LIMK1 (via PDZ & kinase domain); interaction is direct (putative) - interacts with LIMK2; interaction depends on LIMK2 activity (putative). - interacts with RAC1 (activated state) Structure: - homooligomer - both the presence of the PX domain & the coiled coil region are necessary for its endosomal targeting - contains 6 LRR repeats (leucine-rich repeats) - contains 1 PX (phox homology) domain Compartment: - cell membrane, cytoplasm, early endosome recycling endosome - enriched in the early/sorting & recycling endosomes - colocalized in early/sorting endosomes with EEA1 & SNX2 & in recycling endosomes with transferrin receptor - detected in the perinuclear region partially associated with punctate structures (putative) - colocalizes with PAK1 in cytoplasm, vesicular structures in the perinuclear area & membrane ruffles (putative) - colocalizes with RAC1 in the cytoplasm & vesicles structures (putative) - colocalized with MAPK1 & MAPK3 in RVLM neurons (putative) Alternative splicing: named isoforms=4 Expression: - isoform 1, isoform 3 & isoform 4 are expressed in brain - isoform 1 is expressed in endocrine tissues Pharmacology: - rilmenidine activates nischarin producing a hypotensive effect

Properties

SIZE: entity length = 1504 aa MW = 167 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Necessary for binding to phosphoinositide-3-P; not sufficient for targeting to endosomes {1-133} MOTIF: PX domain {11-121} MOTIF: SH3-binding site NAME: SH3-binding site Necessary for homooligomerization & targeting to endosomes {120-695} PAK1 interaction {245-869} MOTIF: leucine-rich repeat SITE: 286-310 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 312-331 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 332-353 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 354-379 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 381-400 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 401-424 MOTIF: leucine residue (SEVERAL) glutamate-rich region {629-691} MOTIF: glutamate residue (SEVERAL) coiled coil {634-695} LIMK interaction {660-869} ITGA5 interaction {709-807} proline-rich region SITE: 1048-1104 MOTIF: proline residue (SEVERAL)

Database Correlations

UniProt Q9Y2I1 PFAM correlations

References

UniProt :accession Q9Y2I1