IRS1 recombinant protein

IRS1 recombinant protein

Cat. Num. AAA515371

• Gene Names: IRS1; HIRS-1
• Applications: Western Blot
• Purity: >80%
• Synonyms: IRS1; IRS1 recombinant protein; Insulin Receptor Substrate 1; HIRS-1

• Host: Sf9 insect cells
• Purity/Purification: >80%
• Form/Format: 50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol.
• Sequence Positions: 600-1245
• Sequence Length: 8743

• Applicable Applications for IRS1 recombinant protein: Kinase Assay, Western Blot (WB)
• Type: Recombinant Fusion Protein
• Accession number: NM 005544
• Species: Human
• Tag Information: GST tag
• Expression System: Sf9 insect cells using baculovirus
• Source Note: Recombinant human IRS1 (600-1245) was expressed by baculovirus in Sf9 insect cells
• Preparation and Storage: Store product at -70°C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.

SDS-PAGE

(The purity of IRS 1 was determined to be >8O% by densitometry. Approx. MW 118kDa.)

Related Product Information for IRS1 recombinant protein

Recombinant human IRS1 (600-1245) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag.

Scientific 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).

Product Categories/Family for IRS1 recombinant protein

Proteins Substrates; Signaling Reagents - Protein Substrates

References

1. Ogihara, T. et al: 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain. J. Biol. Chem. 272: 25267-25274, 1997.
2. Slattery, M.L. et al: Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in outhwestern United States. Breast Cancer Res Treat. 2007.

NCBI and Uniprot Product Information

• NCBI GI #: 187761322
• NCBI GeneID: 3667
• NCBI Accession #: NP_005535.1
• NCBI GenBank Nucleotide #: NM_005544
• UniProt Accession #: P35568
• Molecular Weight: ~118 kDa
• NCBI Official Full Name: Homo sapiens insulin receptor substrate 1 (IRS1), mRNA
• NCBI Official Synonym Full Names: insulin receptor substrate 1
• NCBI Official Symbol: IRS1
• NCBI Official Synonym Symbols: HIRS-1
• NCBI Protein Information: insulin receptor substrate 1; IRS-1
• UniProt Protein Name: Insulin receptor substrate 1
• Protein Family: Isoleucine--tRNA ligase
• UniProt Gene Name: IRS1
• UniProt Synonym Gene Names: IRS-1
• UniProt Entry Name: IRS1_HUMAN

NCBI Description

This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

Uniprot Description

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

By similarity. Ref.14 Ref.30

Subunit structure: Interacts with UBTF and PIK3CA

By similarity. Interacts (via phosphorylated YXXM motifs) with PIK3R1

By similarity. Interacts with ROCK1 and FER

By similarity. Interacts (via PH domain) with PHIP

By similarity. Interacts with GRB2

By similarity. Interacts with SOCS7. Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with ALK. Interacts with EIF2AK2/PKR

By similarity. Ref.5 Ref.6 Ref.7 Ref.10 Ref.11 Ref.14

Post-translational modification: Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor

By similarity. Phosphorylation of Tyr-896 is required for GRB2-binding

By similarity. Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1. Ref.8 Ref.9 Ref.10 Ref.15 Ref.19

Polymorphism: The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance.

Involvement in disease: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.24 Ref.25 Ref.27 Ref.30 Ref.31

Sequence similarities: Contains 1 IRS-type PTB domain.Contains 1 PH domain.