Affinage

NISCH

Nischarin · UniProt Q9Y2I1

Length
1504 aa
Mass
166.6 kDa
Annotated
2026-06-10
100 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NISCH (Nischarin/IRAS) is a cytosolic PX-domain scaffold anchored to the inner face of the plasma membrane that integrates receptor signaling and restrains proliferative and invasive programs (PMID:15028618). It directly associates with insulin receptor substrates IRS-1 through IRS-4 and potentiates insulin-stimulated ERK activation downstream of IRS-4 without altering IRS-4 tyrosine phosphorylation or its coupling to PI3-kinase or Grb2 (PMID:11912194); consistent with an intrinsic role in modulating receptor-driven ERK output, it also confers protection against apoptosis through partial PI3-kinase pathway activation (PMID:15028619). NISCH was originally identified as IRAS, conferring high-affinity I1-imidazoline binding sites, and is specifically required for I1 imidazoline receptor density and moxonidine/agmatine-evoked signaling through ERK, cAMP, calcium, CREB, and c-Fos pathways (PMID:10882231, PMID:17254010, PMID:16962578). Through its PX domain it engages the mu opioid receptor to sort internalized receptor into recycling pathways, accelerating resensitization and limiting desensitization and downregulation, such that its loss exacerbates opioid analgesic tolerance and dependence in vivo (PMID:26363797). As a tumor suppressor, NISCH inhibits FAK and ERK phosphorylation to block cell-cycle progression and invasion, and its silencing—including tobacco-smoke-induced promoter methylation—promotes proliferation and metastasis (PMID:25724667, PMID:23503203).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2000 Medium

    Establishing the molecular identity of the imidazoline I1 receptor was a long-standing pharmacological gap; cloning IRAS provided the first protein reconstituting I1 binding characteristics.

    Evidence cDNA cloning from human hippocampus and heterologous expression with radioligand binding in CHO cells

    PMID:10882231

    Open questions at the time
    • Whether IRAS alone constitutes the I1 receptor or acts within a larger complex was not resolved
    • No structural basis for ligand binding established
  2. 2002 High

    It was unknown how NISCH influences receptor signaling; identifying direct association with IRS proteins placed it as a scaffold that selectively amplifies insulin-driven ERK.

    Evidence Reciprocal Co-IP, mass spectrometry, and domain mapping with ERK and IRS-4 phosphorylation readouts in HEK293 cells

    PMID:11912194

    Open questions at the time
    • Mechanism by which the IRAS-IRS-4 association amplifies ERK without changing IRS-4 phosphorylation not defined
    • Physiological insulin contexts untested
  3. 2003 Medium

    The subcellular basis and signaling polarity of NISCH were unclear; localization studies defined it as a PX-domain-anchored cytosolic protein that modulates ERK and survival signaling.

    Evidence Stable/transient transfection in PC12 and COS7 cells with phospho-ERK, caspase-3, annexin V, and nuclear fragmentation assays

    PMID:15028618 PMID:15028619

    Open questions at the time
    • Direction of ERK modulation differs by context and was not mechanistically reconciled
    • PI3-kinase involvement in survival only partially defined
  4. 2007 High

    Whether NISCH is genuinely required for I1 receptor function rather than merely correlated was open; antisense loss-of-function showed it is specifically needed for I1 binding density and moxonidine-evoked ERK.

    Evidence Antisense knockdown in PC12 cells with radioligand binding and phospho-ERK assays

    PMID:17254010

    Open questions at the time
    • Whether NISCH binds imidazoline ligands directly or assembles a receptor complex unresolved
    • Insulin signaling shown unaffected, but cross-talk not mapped
  5. 2006 Medium

    The downstream effectors of agmatine acting through IRAS at the opioid-relevant I1 receptor were undefined; paired cell-line studies traced effects to cAMP, calcium, CREB, ERK, and c-Fos.

    Evidence Stable MOR/IRAS co-transfection in CHO cells with cAMP, intracellular calcium, and Western blot endpoints under efaroxan antagonism

    PMID:16112088 PMID:16962578

    Open questions at the time
    • Direct coupling between IRAS and these second-messenger pathways not biochemically reconstituted
    • Endogenous neuronal relevance untested
  6. 2015 High

    How NISCH affects opioid receptor fate was unknown; PX-domain-mediated interaction with MOR was shown to route internalized receptor into recycling, with in vivo consequences for tolerance and dependence.

    Evidence Co-IP with PX-domain mutagenesis, receptor recycling/resensitization assays, and IRAS knockout mouse behavior

    PMID:26363797

    Open questions at the time
    • Trafficking machinery linking NISCH-PX to recycling endosomes not identified
    • Lipid/cargo specificity of the PX domain not characterized
  7. 2015 High

    The mechanistic basis of NISCH tumor suppression was unclear; bidirectional manipulation placed it upstream of FAK-ERK to restrain proliferation and invasion.

    Evidence Overexpression/knockdown in ovarian cancer cells, xenografts, and pharmacological FAK-inhibitor epistasis

    PMID:25724667

    Open questions at the time
    • Direct biochemical link between NISCH and FAK not defined
    • Whether scaffolding or enzymatic inhibition underlies FAK suppression unknown
  8. 2013 Medium

    Whether NISCH loss is an early oncogenic event was open; tobacco-smoke induction of promoter methylation in keratinocytes and smoker plasma indicated epigenetic silencing precedes detectable tumors.

    Evidence Quantitative methylation-specific PCR in smoke-exposed cell lines and patient plasma

    PMID:23503203

    Open questions at the time
    • Causal link between methylation and reduced NISCH protein in vivo not demonstrated
    • Single epigenetic method
  9. 2021 Low

    Additional regulatory inputs controlling NISCH levels in cancer were sought; a KLF15/lncRNA/miR-3657 axis was reported to suppress NISCH, which itself limits gastric cancer proliferation and migration.

    Evidence qPCR, Western blot, FISH, miRNA target validation, and proliferation/migration assays in gastric cancer cells

    PMID:34727954

    Open questions at the time
    • Mechanistic placement of the regulatory axis is limited and single-lab
    • Direct miR-3657 targeting of NISCH 3'UTR not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether NISCH binds imidazoline ligands directly or assembles a receptor complex, and how its PX domain mechanistically couples to both endosomal trafficking and FAK-ERK suppression.
  • No structural model of the PX domain or ligand-binding region
  • Direct biochemical effectors linking NISCH to FAK and to recycling endosomes unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 1
Partners
IRS1IRS2IRS3IRS4OPRM1

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 IRAS (imidazoline receptor antisera-selected) cDNA was cloned from a human hippocampal library; the 1504-amino acid protein contains signaling motifs found in cytokine receptors. Transfection of IRAS cDNA into Chinese hamster ovary cells produced high-affinity I1 imidazoline binding sites (nanomolar affinity for moxonidine and rilmenidine), establishing IRAS as the first protein with characteristics of an imidazoline I1 receptor. cDNA cloning, heterologous expression in CHO cells, radioligand binding assay, Western blot with epitope-selective antisera, ruthenium red staining DNA and cell biology Medium 10882231
2002 IRAS associates directly with insulin receptor substrate-4 (IRS-4), and also associates with IRS-1, IRS-2, and IRS-3. Overexpression of IRAS enhanced IRS-4-dependent insulin stimulation of extracellularly regulated kinase (ERK), without altering insulin-stimulated tyrosine phosphorylation of IRS-4 or its association with PI3-kinase or Grb2. The domains of IRAS and IRS-4 responsible for their association were identified by co-immunoprecipitation and mass spectrometry. Co-immunoprecipitation, mass spectrometry, overexpression in HEK293 cells, Western blot for ERK activation and IRS-4 tyrosine phosphorylation The Journal of biological chemistry High 11912194
2003 IRAS is a cytosolic protein anchored to the intracellular side of plasma membranes via a PX domain. Stable transfection of IRAS into PC12 cells resulted in lower basal and NGF-stimulated levels of activated ERK compared to vector-only controls, indicating IRAS intrinsically mediates receptor signaling and modulates ERK activity. Stable transfection in PC12 cells, Western blot for phospho-ERK, subcellular localization analysis Annals of the New York Academy of Sciences Medium 15028618
2003 Human IRAS stably transfected into PC12 cells localizes to the cytosol as a 167 kDa immunoreactive protein. IRAS expression conferred protection against apoptosis induced by serum starvation, thapsigargin, or staurosporine, reducing caspase-3 activity, phosphatidylserine translocation, and nuclear fragmentation. A partial activation of the PI3 kinase pathway was implicated in the anti-apoptotic effect. Stable transfection in PC12 cells, transient transfection in COS7 cells, caspase-3 activity assay, annexin V staining, nuclear fragmentation analysis, immunocytochemistry Annals of the New York Academy of Sciences Medium 15028619
2007 Antisense knockdown of IRAS in PC12 cells significantly reduced I1 imidazoline receptor binding site density (Bmax reduced from 691 to 400 fmol/mg protein) without affecting binding affinity, and attenuated moxonidine-induced ERK activation dose-dependently. Insulin-stimulated ERK activation was unchanged, indicating IRAS is specifically required for I1 receptor signaling. Antisense oligonucleotide transfection in PC12 cells, radioligand binding assay, Western blot for phospho-ERK Journal of neurochemistry High 17254010
2005 IRAS, stably co-expressed with mu opioid receptor (MOR) in CHO cells (CHO-mu/IRAS), was necessary for low concentrations of agmatine (0.1–2.5 µM) to attenuate naloxone-precipitated cAMP overshoot indicative of cellular morphine dependence. This effect was blocked by efaroxan (I1R antagonist) and was absent in CHO-mu cells lacking IRAS, demonstrating IRAS mediates agmatine's high-affinity I1 receptor effects on opioid dependence signaling. Stable co-transfection in CHO cells, cAMP assay, pharmacological antagonism with efaroxan Biochemical pharmacology Medium 16112088
2006 In CHO cells co-expressing MOR and IRAS (CHO-mu/IRAS), agmatine (0.01–3 µM) concentration-dependently inhibited naloxone-precipitated elevation of intracellular calcium concentration; this effect required IRAS and was blocked by efaroxan. Agmatine also attenuated naloxone-precipitated increases in CREB and ERK1/2 phosphorylation and c-Fos expression in CHO-mu/IRAS but not in CHO-mu cells, with all effects blocked by efaroxan. Stable co-transfection in CHO cells, intracellular calcium measurement, Western blot for p-CREB, p-ERK1/2, c-Fos European journal of pharmacology Medium 16962578
2015 IRAS interacts with mu opioid receptor (MOR) through its PX domain (demonstrated in CHO and HEK293 cells co-expressing MOR and IRAS). This interaction facilitated recycling of internalized MOR, prevented DAMGO-induced MOR downregulation, accelerated MOR resensitization, and attenuated MOR desensitization. IRAS knockout mice showed exacerbated analgesic tolerance and physical dependence to opioids. Co-immunoprecipitation, domain deletion/mutation (PX domain), receptor recycling assay, receptor resensitization assay, IRAS knockout mice with behavioral opioid tolerance/dependence assessment Molecular neurobiology High 26363797
2015 NISCH (Nischarin) overexpression in ovarian cancer cells suppressed cell proliferation and colony formation by hindering cell-cycle progression, and attenuated cell invasion by inhibiting phosphorylation of FAK and ERK. In vivo, NISCH-expressing xenografts showed reduced growth, while NISCH knockdown xenografts showed increased peritoneal/pelvic metastases that were blocked by a FAK/Pyk2 inhibitor (PF-562271), placing NISCH upstream of FAK-ERK signaling in invasion suppression. Overexpression and knockdown in ovarian cancer cell lines, colony formation assay, cell cycle analysis, xenograft mouse model, Western blot for p-FAK and p-ERK, pharmacological rescue with FAK inhibitor Molecular cancer therapeutics High 25724667
2013 Tobacco smoke (mainstream and sidestream) induces promoter methylation of the NISCH gene in normal oral keratinocyte cell lines and in plasma of heavy smokers. Promoter methylation of NISCH was detected in 68% of heavy smokers without detectable tumors and in 69% of light smokers with lung cancer, suggesting smoke-induced epigenetic silencing of NISCH precedes detectable cancer. Quantitative fluorogenic real-time methylation-specific PCR in cell lines exposed to cigarette smoke extract and in patient plasma samples Epigenetics Medium 23503203
2021 KLF15-mediated lncRNA TFAP2A-AS1 suppresses NISCH expression via miR-3657 in gastric cancer cells; NISCH was validated as a direct target of miR-3657 and independently suppresses gastric cancer cell proliferation and migration. (Note: this finding relates to regulation of NISCH expression and its functional role in cell proliferation/migration, not to a non-coding RNA product of the NISCH locus itself.) qPCR, Western blot, functional proliferation and migration assays, FISH, miRNA target validation Biology direct Low 34727954

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 1829 10880413
2016 Structure of Mammalian Respiratory Supercomplex I1III2IV1. Cell 309 27912063
1983 Ganglioside GM2 as a human tumor antigen (OFA-I-1). Proceedings of the National Academy of Sciences of the United States of America 200 6193515
2006 Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 176 17015677
2003 Genetic epidemiology of insulin resistance and visceral adiposity. The IRAS Family Study design and methods. Annals of epidemiology 134 12684185
2000 G(i-1)/G(i-2)-dependent signaling by single-transmembrane natriuretic peptide clearance receptor. American journal of physiology. Gastrointestinal and liver physiology 108 10859228
2003 Comparison of the associations of apolipoprotein B and low-density lipoprotein cholesterol with other cardiovascular risk factors in the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 98 14581403
2000 Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization. DNA and cell biology 98 10882231
2005 Involvement of alpha-amylase I-1 in starch degradation in rice chloroplasts. Plant & cell physiology 97 15821023
2009 Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study. Human genetics 87 19322589
2009 Insulin resistance, beta cell dysfunction and visceral adiposity as predictors of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS) Family study. Diabetologia 85 19641896
2002 Angular dependence of 1J(Ni,Calphai) and 2J(Ni,Calpha(i-1)) coupling constants measured in J-modulated HSQCs. Journal of biomolecular NMR 73 12061717
1998 Characterization of a region upstream of exon I.1 of the human CYP19 (aromatase) gene that mediates regulation by retinoids in human choriocarcinoma cells. Endocrinology 66 9528950
2014 GE23077 binds to the RNA polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides. eLife 65 24755292
2005 Sol i 1, the phospholipase allergen of imported fire ant venom. The Journal of allergy and clinical immunology 65 15753912
2010 Molecular basis of a linkage peak: exome sequencing and family-based analysis identify a rare genetic variant in the ADIPOQ gene in the IRAS Family Study. Human molecular genetics 63 20688759
2006 Confirmation of the origin of NISCH syndrome. Human mutation 61 16619213
2004 Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans: the insulin resistance atherosclerosis study (IRAS) family study. Diabetes 61 15504985
2014 Back pocket flexibility provides group II p21-activated kinase (PAK) selectivity for type I 1/2 kinase inhibitors. Journal of medicinal chemistry 59 24432870
1998 NMR spectroscopic studies of I = 1/2 metal ions in biological systems. Biochemistry and cell biology = Biochimie et biologie cellulaire 58 9923691
2000 Cloning and functional analysis of chicory root fructan1-exohydrolase I (1-FEH I): a vacuolar enzyme derivedfrom a cell-wall invertase ancestor? Mass fingerprint of the 1-FEH I enzyme. The Plant journal : for cell and molecular biology 56 11115126
2000 Coupling of I(1) imidazoline receptors to the cAMP pathway: studies with a highly selective ligand, benazoline. Molecular pharmacology 54 10825384
2005 Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study. Human genetics 51 15843989
2005 Thermostability and in vitro digestibility of a purified major allergen 2S albumin (Ses i 1) from white sesame seeds (Sesamum indicum L.). Biochimica et biophysica acta 50 16140598
2004 Identification of quantitative trait loci for glucose homeostasis: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes 50 15220212
2002 Insulin receptor substrate 4 associates with the protein IRAS. The Journal of biological chemistry 46 11912194
2021 Ultrathin 2D Copper(I) 1,2,4-Triazolate Coordination Polymer Nanosheets for Efficient and Selective Gene Silencing and Photodynamic Therapy. Advanced materials (Deerfield Beach, Fla.) 45 33797149
2006 Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene: the IRAS family study. Diabetes 44 16731835
2006 Effects of i and i+3 residue identity on cis-trans isomerism of the aromatic(i+1)-prolyl(i+2) amide bond: implications for type VI beta-turn formation. Biopolymers 43 16208767
2000 Protein phosphatase 2A inhibitors, I(1)(PP2A) and I(2)(PP2A), associate with and modify the substrate specificity of protein phosphatase 1. The Journal of biological chemistry 42 10734057
1994 1462V mutation in the human CYP1A1 gene: lack of correlation with either the Msp I 1.9 kb (M2) allele or CYP1A1 inducibility in a three-generation family of east Mediterranean descent. Pharmacogenetics 41 7516235
1995 Modeling protein loops using a phi i + 1, psi i dimer database. Protein science : a publication of the Protein Society 40 7670382
2006 Uptake of 2S albumin allergens, Ber e 1 and Ses i 1, across human intestinal epithelial Caco-2 cell monolayers. Journal of agricultural and food chemistry 39 17061844
2000 Heterologous desensitization of response mediated by selective PKC-dependent phosphorylation of G(i-1) and G(i-2). American journal of physiology. Cell physiology 39 11003572
2020 In vivo Activity of Copper(II), Manganese(II), and Silver(I) 1,10-Phenanthroline Chelates Against Candida haemulonii Using the Galleria mellonella Model. Frontiers in microbiology 37 32265890
1993 Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity. Experimental hematology 36 8417953
2007 Sphingosine-1-phosphate reduces CD4+ T-cell activation in type 1 diabetes through regulation of hypoxia-inducible factor short isoform I.1 and CD69. Diabetes 34 18003758
2003 Cell signaling by imidazoline-1 receptor candidate, IRAS, and the nischarin homologue. Annals of the New York Academy of Sciences 33 15028618
2001 Imidazoline I(1) receptor-induced activation of phosphatidylcholine-specific phospholipase C elicits mitogen-activated protein kinase phosphorylation in PC12 cells. European journal of pharmacology 33 11274989
2019 Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS). BMJ open diabetes research & care 32 31543975
2004 Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases. Cancer letters 32 15072822
2013 Pharmacological modulation of I(1)-imidazoline and α2-adrenoceptors in sub acute brain ischemia induced vascular dementia. European journal of pharmacology 31 24333661
2007 Identification of IRAS/Nischarin as an I1-imidazoline receptor in PC12 rat pheochromocytoma cells. Journal of neurochemistry 31 17254010
2000 Effects of the I(1) imidazoline/alpha(2)-adrenergic receptor agonist moxonidine in comparison with clonidine in the formalin test in rats. Pain 31 10692615
2006 Genetic mapping of disposition index and acute insulin response loci on chromosome 11q. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes 30 16567510
2009 Facilitation of central imidazoline I(1)-site/extracellular signal-regulated kinase/p38 mitogen-activated protein kinase signalling mediates the hypotensive effect of ethanol in rats with acute renal failure. British journal of pharmacology 29 19845670
2005 IRAS, a candidate for I1-imidazoline receptor, mediates inhibitory effect of agmatine on cellular morphine dependence. Biochemical pharmacology 29 16112088
1991 Expression of a G protein subunit, alpha i-1, in Balb/c 3T3 cells leads to agonist-specific changes in growth regulation. The Journal of biological chemistry 29 1939086
2019 Diagnosis of Sesame Allergy: Analysis of Current Practice and Exploration of Sesame Component Ses i 1. The journal of allergy and clinical immunology. In practice 28 31786253
2005 Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study. International journal of obesity (2005) 28 15672110
2021 Transcription factor KLF15 inhibits the proliferation and migration of gastric cancer cells via regulating the TFAP2A-AS1/NISCH axis. Biology direct 27 34727954
2011 Imidazoline antihypertensive drugs: selective i(1) -imidazoline receptors activation. Cardiovascular therapeutics 27 21884004
2005 Antigen-induced Ca2+ mobilization in RBL-2H3 cells: role of I(1,4,5)P3 and S1P and necessity of I(1,4,5)P3 production. Cell calcium 27 16219349
1994 Effects of anti-CD44 monoclonal antibody on adhesion of erythroid leukemic cells (ELM-I-1) to hematopoietic supportive cells (MS-5): CD44, but not hyaluronate-mediated, cell-cell adhesion. Experimental hematology 26 7514542
2016 Cloning, expression, and purification of recombinant major mango allergen Man i 1 in Escherichia coli. Protein expression and purification 25 27350535
2014 Pharmacological benefit of I(1)-imidazoline receptors activation and nuclear factor kappa-B (NF-κB) modulation in experimental Huntington's disease. Brain research bulletin 25 24582883
2013 RETRACTED ARTICLE: Enhanced glycemic control, pancreas protective, antioxidant and hepatoprotective effects by umbelliferon-α-D-glucopyranosyl-(2(I) → 1(II))-α-D-glucopyranoside in streptozotocin induced diabetic rats. SpringerPlus 25 24349947
2011 Lifestyle factors and 5-year abdominal fat accumulation in a minority cohort: the IRAS Family Study. Obesity (Silver Spring, Md.) 25 21681224
2001 Secondary structure of human apolipoprotein A-I(1-186) in lipid-mimetic solution. FEBS letters 25 11163364
1999 Karyotypic evolution in breast carcinomas with i(1)(q10) and der(1;16)(q10;p10) as the primary chromosome abnormality. Cancer genetics and cytogenetics 25 10484983
1993 Comparison of the immunocytochemical localization of DARPP-32 and I-1 in the amygdala and hippocampus of the rhesus monkey. The Journal of comparative neurology 25 8408754
2017 Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine. Journal of medicinal chemistry 24 28834431
2007 The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study. BMC endocrine disorders 24 17397545
2003 Pleiotropy and heterogeneity in the expression of atherogenic lipoproteins: the IRAS Family Study. Human heredity 24 12890925
2003 IRAS is an anti-apoptotic protein. Annals of the New York Academy of Sciences 24 15028619
2019 Molecular dynamics simulation and QM/MM calculation reveal the selectivity mechanism of type I 1/2 kinase inhibitors: the effect of intramolecular H-bonds and conformational restriction for improved selectivity. Physical chemistry chemical physics : PCCP 23 31657381
2013 Cigarette smoke induces methylation of the tumor suppressor gene NISCH. Epigenetics 22 23503203
2007 S1P-receptors in PC12 and transfected HEK293 cells: molecular targets of hypotensive imidazoline I(1) receptor ligands. Neurochemistry international 22 17559976
2000 The cisproline(i - 1)-aromatic(i) interaction: folding of the Ala-cisPro-Tyr peptide characterized by NMR and theoretical approaches. Journal of biomolecular NMR 22 10909867
2011 Cloning and characterization of 2S albumin, Car i 1, a major allergen in pecan. Journal of agricultural and food chemistry 21 21395309
2007 I(1)-superfamily conotoxins and prediction of single D-amino acid occurrence. Toxicon : official journal of the International Society on Toxinology 21 17996262
2020 The Use of the Selective Imidazoline I1 Receptor Agonist Carbophenyline as a Strategy for Neuropathic Pain Relief: Preclinical Evaluation in a Mouse Model of Oxaliplatin-Induced Neurotoxicity. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20 32572830
2018 Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS). The Journal of clinical endocrinology and metabolism 20 29546329
2017 Umbelliferon-α-d-glucopyranosyl-(2I→1II)-α-Dglucopyranoside ameliorates Diethylnitrosamine induced precancerous lesion development in liver via regulation of inflammation, hyperproliferation and antioxidant at pre-clinical stage. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 28802237
2015 Frequent Loss of NISCH Promotes Tumor Proliferation and Invasion in Ovarian Cancer via Inhibiting the FAK Signal Pathway. Molecular cancer therapeutics 20 25724667
2005 A genome scan for fasting insulin and fasting glucose identifies a quantitative trait locus on chromosome 17p: the insulin resistance atherosclerosis study (IRAS) family study. Diabetes 20 15616041
1992 Follicle-stimulating hormone increases guanine nucleotide-binding regulatory protein subunit alpha i-3 mRNA but decreases alpha i-1 and alpha i-2 mRNA in Sertoli cells. Molecular endocrinology (Baltimore, Md.) 20 1328874
2021 Combinatorial advantage of Ses i 1-specific IgE and basophil activation for diagnosis of sesame food allergy. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 19 33955090
2004 pp32/ I-1(PP2A) negatively regulates the Raf-1/MEK/ERK pathway. Cancer letters 19 16039954
2003 The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat model of metabolic syndrome X. The Journal of pharmacology and experimental therapeutics 19 12756274
2004 Association analysis of the plasminogen activator inhibitor-1 4G/5G polymorphism in Hispanics and African Americans: the IRAS family study. Human heredity 18 15297806
2002 Transcriptional effects of the potent enediyne anti-cancer agent Calicheamicin gamma(I)(1). Chemistry & biology 18 11880039
2015 A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). PloS one 17 26599207
2012 The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia 17 23052060
2006 Modulation of agmatine on calcium signal in morphine-dependent CHO cells by activation of IRAS, a candidate for imidazoline I1 receptor. European journal of pharmacology 17 16962578
2022 Terbium-Doped and Dual-Passivated γ-CsPb(I1- x Brx )3 Inorganic Perovskite Solar Cells with Improved Air Thermal Stability and High Efficiency. Advanced materials (Deerfield Beach, Fla.) 16 35581144
2021 Biocontrol mechanism of Myxococcus xanthus B25-I-1 against Phytophthora infestans. Pesticide biochemistry and physiology 16 33993957
2013 Genetic deletion of the HIF-1α isoform I.1 in T cells enhances antibacterial immunity and improves survival in a murine peritonitis model. European journal of immunology 16 23208786
2011 RGS6 variants are associated with dietary fat intake in Hispanics: the IRAS Family Study. Obesity (Silver Spring, Md.) 16 21233807
2004 Insulin sensitivity, body fat distribution, and family diabetes history: the IRAS Family Study. Obesity research 16 15166304
1997 Epidermal growth factor activates phospholipase C-gamma 1 via G(i)1-2 proteins in isolated pancreatic acinar membranes. The American journal of physiology 16 9176240
2020 Molecular and immunological characterization of grass carp (Ctenopharyngodon idella) parvalbumin Cten i 1: A major fish allergen in Hong Kong. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 15 32323392
2020 Bioisosteric Replacement of Arylamide-Linked Spine Residues with N-Acylhydrazones and Selenophenes as a Design Strategy to Novel Dibenzosuberone Derivatives as Type I 1/2 p38α MAP Kinase Inhibitors. Journal of medicinal chemistry 15 32462866
2013 Decrease of Obesity by Allantoin via Imidazoline I 1 -Receptor Activation in High Fat Diet-Fed Mice. Evidence-based complementary and alternative medicine : eCAM 15 23606885
2008 Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome). Experimental dermatology 15 18095941
2008 Effects of spinal alpha(2)-adrenoceptor and I(1)-imidazoline receptor activation on hindlimb movement induction in spinal cord-injured mice. The Journal of pharmacology and experimental therapeutics 15 18364473
2003 The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase. Brain research 15 12865160
1993 Follicle-stimulating hormone increases the turnover of G-protein alpha i-1- and alpha i-2-subunit messenger RNA in Sertoli cells by a mechanism that is independent of protein synthesis. Molecular endocrinology (Baltimore, Md.) 15 8483480
2022 Copper(II) and silver(I)-1,10-phenanthroline-5,6-dione complexes interact with double-stranded DNA: further evidence of their apparent multi-modal activity towards Pseudomonas aeruginosa. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 14 35006347
2015 IRAS Modulates Opioid Tolerance and Dependence by Regulating μ Opioid Receptor Trafficking. Molecular neurobiology 14 26363797

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