Product Name:
IRS1-pY612
Product Number:
ab-pn960
Target Full Name: Insulin receptor substrate 1
Target Alias: HIRS-1; Insulin receptor substrate-1; IRS-1
Product Type Specific: IRS1 phosphosite-specific antibody
Antibody Code: PN960
Antibody Target Type: Phosphosite-specific
Antibody Phosphosite: Y612
Protein UniProt: P35568
Protein SigNET: IRS1
Antibody Type: Polyclonal
Antibody Host Species: Rabbit
Antibody Immunogen Source: Synthetic phosphopeptide patterned after human IRS1
Antibody Immunogen Sequence: TDDG(pY)MPMSC
Antibody Immunogen Description: Corresponds to amino acid residues T608 to S616. Y612 phosphorylation induces interaction with PI3KR1. This is a major in vivo phosphorylation site in IRS1 (≥304 reports from high throughput mass spectrometry studies recorded in PhosphoSitePlus). IRS1 is known to be phosphorylated at this site in vitro by InsR.
Production Method: The immunizing peptide was produced by solid phase synthesis on a multipep peptide synthesizer and purified by reverse-phase hplc chromatography. Purity was assessed by analytical hplc and the amino acid sequence confirmed by mass spectrometry analysis. This peptide was coupled to KLH prior to immunization into rabbits. New Zealand White rabbits were subcutaneously injected with KLH-coupled immunizing peptide every 4 weeks for 4 months. The sera from these animals was applied onto an agarose column to which the immunogen peptide was thio-linked. Antibody was eluted from the column with 0.1 M glycine, pH 2.5. Subsequently, the antibody solution was neutralized to pH 7.0 with saturated Tris.
Antibody Modification: Unconjugated. Contact KInexus if you are interest in having the antibody biotinylated or coupled with fluorescent dyes.
Antibody Concentration: 0.1 mg/ml
Storage Buffer: Phosphate buffered saline pH 7.4, 0.05% Thimerasol
Storage Conditions: For long term storage, keep frozen at -40°C or lower. Stock solution can be kept at +4°C for more than 3 months. Avoid repeated freeze-thaw cycles.
Product Use: Western blotting | Antibody microarray
Antibody Dilution Recommended: 2 µg/ml for immunoblotting
Antibody Species Reactivity: This antibody detects the target phosphoprotein in the following species due to conservation of amino acid sequence: Human | Chimpanzee | Rhesus macaque | Dog | Rat | Mouse | Chicken | Zebra fish.
Related Product 1: IRS1 S636+S639 phosphorylation antibody (Cat. No.: AB-PN831)
Related Product 2: IRS1 Y632 phosphorylation antibody (Cat. No.: AB-PN1032)
Scientific Background: IRS1 (Insulin receptor substrate 1) is a cytoplasmic, adaptor scaffolding protein that mediates the control of various cellular processes by insulin and insulin-like growth factor 1 (IGF1). It functions in development, growth, glucose homeostasis as well as lipid metabolism. It size varies from 132 to 180 kDa due to extensive phosphorylation on tyrosine as well as serine and theronine residues, When phosphorylated by the insulin receptor, it binds specifically to various cellular proteins with SH2 domains such as p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2. It activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit. Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1, which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade. Activation of the PI3K/AKT pathway is responsible for most of the metabolic effects of insulin on cells, and the involvement of the Ras/Raf/MEK/MAPK pathway permits cooperation with the PI3K pathway to regulate cell growth and differentiation. It is crucial for glucose homeostasis, particularly regulating Akt phosphorylation and GLUT4 translocation in muscle and adipose tissues. IRS1 also features a pleckstrin homology (PH) domain and a phosphotyrosine-binding (PTB) domain at the N-terminus, which are essential for its interaction with Insulin and IGF1 receptors in the plasma membrane. IRS1 can also be found in the nucleus of cells. IRS1 is a PEST protein (rich in proline, glutamic acid, serine, and threonine), which allows it to be rapidly degraded by calpains upon insulin stimulation to regulate the signal strength. Dysfunction or reduced expression of IRS1 is linked to Type 2 diabetes due to insulin resistance, as well as to cancer, where it acts as an oncogene promoting tumour growth and proliferation. This description may include information annotated by UniProt and/or Google AI.