Nischarin

Function

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). Also inhibits 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.

Classification

Family (Pfam)

PF25625 PH_NISCH_C, PF23142 PH_PLEKHM2, PF00787 PX

InterPro

Leu-rich_rpt, LRR_dom_sf, Nischarin_PX, PH_NISCH_C, PH_PLEKHM2, PX_dom, PX_dom_sf

Functional cluster

Eukaryotic Transcription Factors & related

Experimental structures · PDB · 2

• 3P0C X-ray 2.27A
• 8ESF X-ray 2.56A

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0005829 cytosol
• GO:0005769 early endosome
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0055037 recycling endosome
• GO:0005178 integrin binding
• GO:0035091 phosphatidylinositol binding
• GO:0006915 apoptotic process
• GO:0016601 Rac protein signal transduction

Drugs targeting this protein · 2

• MOXONIDINE agonist
• RILMENIDINE agonist

Related proteins · sequence + function similarity

• Nischarin 0.97
• Nischarin 0.96
• Serine/threonine-protein kinase 11-interacting protein 0.82
• Serine/threonine-protein kinase 11-interacting protein 0.79
• Malignant fibrous histiocytoma-amplified sequence 1 0.72
• Serine/threonine-protein kinase 11-interacting protein 0.71
• Malignant fibrous histiocytoma-amplified sequence 1 homolog 0.71
• BLOC-2 complex member HPS5 0.70
• Leucine-rich repeat serine/threonine-protein kinase 1 0.68
• Leucine-rich repeat serine/threonine-protein kinase 1 0.67
• Pleckstrin homology domain-containing family M member 1 0.66
• Malignant fibrous histiocytoma-amplified sequence 1 homolog 0.66

Co-cited proteins · studied together in the literature

• Serine/threonine-protein kinase STK11 1 shared papers
• Insulin receptor substrate 4 1 shared papers
• Integrin alpha-5 1 shared papers
• Mitogen-activated protein kinase 3 1 shared papers
• Mitogen-activated protein kinase 1 1 shared papers
• Phosphatidylinositol 3-kinase regulatory subunit alpha 1 shared papers
• Growth factor receptor-bound protein 2 1 shared papers

Literature · 17 cited papers

• Integrin-binding protein nischarin interacts with tumor suppressor liver kinase B1 (LKB1) to regulate cell migration of breast epithelial cells. J. Biol. Chem. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
• The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Human Nischarin/imidazoline receptor antisera-selected protein is targeted to the endosomes by a combined action of a PX domain and a coiled-coil region. J. Biol. Chem. · 2004
• IRAS splice variants. Ann. N. Y. Acad. Sci. · 2003
• IRAS is an anti-apoptotic protein. Ann. N. Y. Acad. Sci. · 2003
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• … and 5 more in the literature graph