Recombinant Human IRS1 (N-Term) Protein

Name: Recombinant Human IRS1 (N-Term) Protein
Brand: Beta LifeScience
SKU: BL-1051SG
Availability: InStock

Collections: All products, High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Tag	GST
Host Species	Human
Accession	NM_005544
Synonym	HIRS-1
Background	IRS1 is the substrate for the insulin tyrosine kinase receptor and is found in a variety of insulin-responsive cells and tissues. IRS1 protein has no intrinsic enzymatic activity but acts as a docking protein, via the SH2 domains, for mediating the insulin downstream signaling events. IRS1 has been shown to associate with the 14-3-3 family of proteins and this could play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS1 (1). IRS1 may be associated with colorectal cancer and diet and related factors may affect the risk by modifying plasma insulin levels. Thus, the inter-individual variation in insulin signaling mediated by IRS1 may play a plausible role in the development of colorectal cancer (2).
Description	Recombinant human IRS1 (1-355) was produced in E. coli system, fused with a GST tag at N-terminus. This protein is purified with our unique purification methods.
Source	E.coli
AA Sequence	1-355
Molecular Weight	~65 kDa
Purity	For specific purity information on a given lot, see related COA.
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Formulation	Recombinant protein is supplied in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM Glutathione, 0.25mM DTT, 0.1mM EDTA, 0.1mM PMSF and 25% glycerol.
Stability	The recombinant protein is stable for up to 12 months at -70°C
Usage	For Research Use Only
Storage	Recombinant Human IRS1 (N-Term) Protein should be stored should be stored at < -70°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function

May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit.

Database References

HGNC: 6125

OMIM: 125853

KEGG: hsa:3667

STRING: 9606.ENSP00000304895

UniGene: PMID: 29970713

our findings suggested that the overexpression of LncRNA H19 could inhibit cell proliferation and promoted apoptosis via downregulation of IRS-1 in thyroid cancer cells in vitro. These findings might provide important clues for the establishment of LncRNA H19 functional network in thyroid cancer. Long noncoding RNA H19 might be a potential new target for antitumor therapy of thyroid cancer PMID: 29332545

Acute loss of IRS1/IRS2 or inhibition of IR/IGF1R in KRAS-mutant human NSCLC cells decreases the uptake and lowers the intracellular levels of amino acids, while enhancing basal autophagy and sensitivity to autophagy and proteasome inhibitors. PMID: 29610318

S6K1-dependent IRS-1pSer suppresses insulin signaling leading to insulin resistance, which is frequently observed in AD brains. Notably, miR-200b/c transfection of SH-SY5Y cells reduced the levels of IRS-1pSer. This finding indicates that miR-200b/c has the potential to alleviate insulin resistance via modulation of S6K1 PMID: 29738527

Together, miR-145 mimics suppress cell proliferation by targeting and inhibiting IRS1 expression to inhibit MAPK/ERK signaling pathways. PMID: 27799458

Data suggest that Y537S/D538G ESR1 mutant breast cancer cell lines exhibit enhanced proliferation in response to IGF1/IGF1R signaling; mechanism involves IRS1; here, knockdown of IRS1 attenuates enhanced IGF1/IGF1R signaling response in ESR1 mutant cells. (ESR1 = estrogen receptor 1; IGF1 = insulin like growth factor 1; IGF1R = IGF1 receptor; IRS1 = insulin receptor substrate 1) PMID: 29029116

The effect of PF may be associated with its role in inhibiting de novo lipid synthesis and in regulating the ROCK/IRS/Akt signalling pathways. PMID: 28380411

Gene expression for insulin receptor substrate 1 (IRS-1), protein kinase B (Akt-2) and glucose transporter 4 (GLUT-4) genes were evaluated by real time PCR. PMID: 28364599

Reduced insulin receptor substrate-1 (IRS-1) staining in lung adenocarcinoma tissue microarray displayed a significant survival disadvantage, especially within the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant subgroup. PMID: 27439864

This study examined the normal regional brain expression of IRS-1 and found a significant correlation with the volumetric associated with regional atrophy in Alzheimer's disease. PMID: 28105773

Data show that MIR126 induces autophagic flux in malignant mesothelioma (MM) cells by downregulating insulin receptor substrate-1 (IRS1) and disrupting the IRS1 signaling pathway. PMID: 27119351

IRS1/beta-Catenin Axis Is Activated and Induces MYC Expression in Acute Lymphoblastic Leukemia Cells PMID: 27987331

These effects were exerted by changes on the phosphorylation of IRS-1. PMID: 28011403

Allele and genotype frequencies of rs1801278 in IRS1 showed significant differences between cases and controls for obstructive sleep apnea risk in Chinese Han population. PMID: 27509181

Gly972Arg of IRS-1 polymorphisms are associated with polycystic ovary syndrome. PMID: 27785750

G allele of the rs7578326 SNP in the LOC646736/IRS1 region is significantly associated with gestational diabetes mellitus. PMID: 28072873

The results suggest that high glucose compromises the insulin signaling pathway in the glomerulus, promoting a proapoptotic environment, with a possible critical step for this malfunction lying at the level of IRS-1 phosphorylation. PMID: 27434075

The C-allele of IRS1 variant rs2943650 was significantly associated with higher Body Fat Percentage overall and was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol in United States Hispanics/Latinos. PMID: 27663718

IRS-1 and IRS-2 signaling interaction with the microtubule cytoskeleton and its response to AKT determines the response to microtubule disruption in breast carcinoma cells PMID: 28320862

Consistent with these observations, LPIN1 levels were positively correlated with IRS1 expression in human breast cancer. Thus, our results indicate a mechanism by which IRS1 expression is increased in breast cancer, and LPIN1 may be a promising drug target for anticancer therapy PMID: 27729374

IRS1 Gene Polymorphism is associated with Autism Spectrum Disorder. PMID: 27483248

High IRS1 expression is associated with hepatocellular carcinoma. PMID: 27542674

In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. PMID: 27247938

miR-195 inhibits tumor angiogenesis through suppressing IRS1-VEGF axis. PMID: 27133044

The Arg(972) IRS-1 polymorphism is associated with increased risk and disease activity/severity of rheumatoid arthritis, and therefore may be a potential prognostic factor for RA. PMID: 25424426

In this exploratory analysis, IRS1, ENNP1 and TRIB3, known to be associated with type 2 diabetes and harboring genes playing a prominent role in mediating insulin signaling, may modulate a number of cardiometabolic phenotypes in patients of Italian ancestry with newly-diagnosed type 2 diabetes. PMID: 26868433

In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for colorectal cancer (CRC) in overweight/obese patients and for obesity in patients with CRC. PMID: 26349669

FRET-based translocation assays reveal that insulin promotes the association of both p62 and aPKC with the insulin-regulated scaffold IRS-1. PMID: 27143478

HCV NS5A favors serine phosphorylation of IRS-1, promoting insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis. PMID: 26604643

High IRS1 Expression is associated with Colorectal Cancer. PMID: 26577117

failed to find any association between the IRS1 Gly972Arg polymorphism and T2DM PMID: 26620983

rs1801278 in IRS1 gene may play a role in type 2 diabetes risk, especially in Asian and rs2943641 may be associated with type 2 diabetes risk in Caucasian.[meta-analysis] PMID: 26582067

Upregulation of IRS1 was associated with metastasis of gastric carcinoma. PMID: 26684358

The G allele of rs13431554 in the IRS-1 gene was associated with a hyperreactive platelet phenotype in the coronary artery disease patients with T2DM. PMID: 27005817

miR-126 functions as a tumor suppressor in glioma cells by targeting IRS-1 expression via the PI3K/AKT signaling pathways PMID: 26617742

Results showd that miR-128 was negatively associated with IRS1 in colorectal carcinoma (CRC) tissues and suggested that miR-128 serves as a tumor suppressor and blocks CRC growth and metastasis by targeting IRS1. PMID: 26352220

IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer. PMID: 26991655

Data suggest that IRS1 tyrosine phosphorylation, insulin sensitivity, and glucose internalization in visceral adipocytes can be up-regulated by dietary components (here, protocatechuic acid, a metabolite of dietary anthocyanins). PMID: 25944785

genetic association studies in population in Austria: Data suggest that a haplotype upstream of IRS1 protects against insulin resistance, type 2 diabetes, dyslipidemias, and atherosclerosis. PMID: 26090471

Arg972 IRS-1 inhibits endothelial nitric oxide synthase expression in human endothelial cells by upregulating miR-155 expression through the impairment of phosphatidylinositol-3 kinase signaling. PMID: 25902041

Alpha-Syn overexpression negatively regulated IRS-1 via mTORC1/S6K1 signaling while activation of PP2A reverses this process. PMID: 25813876

hepatic insulin resistance in human obesity is: advanced; BMI-correlated; and involves aPKC-activating ceramide; aPKC levels and activity; IRS-1 levels, Akt activity, and FoxO1 phosphorylation; and increases in expression/abundance of PGC-1alpha PMID: 26386696

Arg972 IRS-1 enhances TNF-alpha-induced apoptosis in osteoblasts from rheumatoid arthritis patients. PMID: 25760103

Hepatitis C virus infection suppresses the insulin signaling pathway and promotes insulin resistance by repressing PTEN, subsequently leading to decreased levels of IRS-1 and increased levels of Ser307-phosphorylated IRS-1. PMID: 25645159

AFB1 downregulates IRS1 but paradoxically upregulates IRS2 through positive regulation of the stability of IRS2 and the proteasomal degradation of IRS1 in lung cancer cell lines A549 and SPCA-1. PMID: 25820822

Gly972Arg was not associated with obesity, insulin resistance/sensitivity or type 2 diabetes mellitus PMID: 25214251

Results show that in esophageal squamous cell carcinoma (ESCC), miR-126 was downregulated and IRS-1 and GOLPH3, overexpressed suggesting a tumor suppression role of miR-126 via the regulation of IRS-1 and GOLPH3. PMID: 25017784

our study found that the genetic polymorphisms rs10830963 and rs1387153 in MTNR1B and rs1801278 in IRS1 were associated with an increased risk of developing GDM. PMID: 25146448

Results suggest that a genetic variation in the insulin signaling pathway genes IRS1, IRS2 and INSR may affect the therapeutic response of temporal lobe epilepsy PMID: 25458098

N-myristoylated Cblin prevents DEX-induced skeletal muscle atrophy in vitro and in vivo, and N-myristoylated Cblin more effectively prevents muscle atrophy than unmodified Cblin PMID: 25689493

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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