NISCH

This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor. [provided by RefSeq, Jan 2013]

Nischarin

Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity).
Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity).
Acts as a modulator of Rac-regulated signal transduction pathways (By similarity).
Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity).
Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity).
Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity).
Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity).
Inhibits lamellipodia formation, when overexpressed (By similarity).
Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures.

Actin cytoskeleton organizationIEA:Ensembl
Apoptotic processIEA:UniProtKB-KW
Negative regulation of cell migrationIEA:Ensembl
Rac protein signal transductionIEA:Ensembl

Cell membrane
Cytoplasm
Early endosome
Recycling endosome
Enriched in the early/sorting and recycling endosomes. Colocalized in early/sorting endosomes with EEA1 and SNX2 and in recycling endosomes with transferrin receptor. Detected in the perinuclear region partially associated with punctate structures (By similarity).
Colocalizes with PAK1 in cytoplasm, vesicular structures in the perinuclear area and membrane ruffles (By similarity).
Colocalizes with RAC1 in the cytoplasm and vesicles structures (By similarity).
Colocalized with MAPK1 and MAPK3 in RVLM neurons (By similarity).