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)
Jump to navigation
Jump to search
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
Pharmacology
- rilmenidine activates nischarin producing a hypotensive effect