Tclin NISCH Nischarin

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• Q9Y2I1
• C9J245
• Q6PGP3
• Q6PIB4
• Q7L8M3
• Q7Z2X6
• Q9UES6
• Q9UEU4
• Q9UFW3

Gene Name

• NISCH

Ensembl ID

• ENST00000345716
• ENSP00000339958
• ENSG00000010322
• ENST00000420808
• ENSP00000392484
• ENST00000479054
• ENSP00000418232

Symbol

• IRAS
• KIAA0975
• I-1
• IR1
• IRAS
• hIRAS

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.95
transcription factor perturbation	0.94
disease perturbation	0.74
molecular function	0.73
drug perturbation	0.71

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Nischarin

DTO Classes

Protein / Enzyme Modulator / Nischarin

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 999.78   (req: < 5)

Gene RIFs: 28   (req: <= 3)

Antibodies: 93   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 999.78   (req: >= 5)

Gene RIFs: 28   (req: > 3)

Antibodies: 93   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 134

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 8