Rabbit anti-Human Insulin Receptor Polyclonal Antibody | anti-INSR antibody

Insulin Receptor Antibody

Cat. Num. AAA9613977

• Gene Names: INSR; HHF5; CD220
• Reactivity: Human
• Applications: ELISA
• Purity: The antiserum was purified by peptide affinity chromatography using SulfoLink Coupling Resin
• Synonyms: Insulin Receptor; Polyclonal Antibody; Insulin Receptor Antibody; CD220; HHF5; human insulin receptor; Insr; INSR_HUMAN; IR 1; IR; IR-1; IR1; anti-INSR antibody

• Host: Rabbit
• Reactivity: Human
• Clonality: Polyclonal
• Isotype: Rabbit IgG
• Specificity: IR Antibody detects endogenous levels of IR.; Tissue Specificity: Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.
• Purity/Purification: The antiserum was purified by peptide affinity chromatography using SulfoLink Coupling Resin
• Form/Format: Liquid. Rabbit IgG in phosphate buffered saline, pH7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
• Concentration: 1mg/ml (varies by lot)

• Applicable Applications for anti-INSR antibody: Peptide ELISA (EIA)
• Application Notes: Peptide ELISA: 1:20,000-1:40,000
• Immunogen: A synthesized peptide derived from human IR.
• Conjugation: Unconjugated
• Fragment: Fab fragment
• Post Translational Modifications: After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane. Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-999 is required for binding to IRS1, SHC1 and STAT5B. Dephosphorylated by PTPRE at Tyr-999, Tyr-1185, Tyr-1189 and Tyr-1190. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.
• Subunit Structure: Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains carry the insulin-binding regions, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 (By similarity). Interacts with ARRB2 (By similarity). Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with GRB7. Interacts with PDPK1. Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-999, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF. Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity). Interacts with the cone snail venom insulin Con-Ins G1. Interacts with the insulin receptor SORL1; this interaction strongly increases its surface exposure, hence strengthens insulin signal reception. Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the INSR C-terminal region. Interacts with GNAI3; the interaction is probably mediated by CCDC88A/GIV.
• Similarity: The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2.Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
• Subcellular Location: Cell membrane>Single-pass type I membrane protein. Late endosome. Lysosome.; Note: Binding of insulin to INSR induces internalization and lysosomal degradation of the receptor, a means for downregulating this signaling pathway after stimulation. In the presence of SORL1, internalized INSR molecules are redirected back to the cell surface, thereby preventing their lysosomal catabolism and strengthening insulin signal reception.
• Preparation and Storage: Store at -20 degree C. Stable for 12 months from date of receipt.

Related Product Information for anti-INSR antibody

Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol- (3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. Shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast,shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity).
The human insulin receptor is a heterotetrameric membrane glycoprotein consisting of disulfide linked subunits in a beta-alpha-alpha-beta configuration. The beta subunit (95kDa) possesses a single transmembrane domain, whereas the alpha subunit (135kDa) is completely extracellular. The insulin receptor exhibits receptor tyrosine kinase (RTK) activity. RTKs are single pass transmembrane receptors that possess intrinsic cytoplasmic enzymatic activity, catalyzing the transfer of the gamma phosphate of ATP to tyrosine residues in protein substrates. RTKs are essential components of signal transduction pathways that affect cell proliferation, differentiation, migration and metabolism. Included in this large protein family are the insulin receptor and the receptors for growth factors such as epidermal growth factor, fibroblast growth factor and vascular endothelial growth factor. Receptor activation occurs through ligand binding, which facilitates receptor dimerization and autophosphorylation of specific tyrosine residues in the cytoplasmic portion. The interaction of insulin with the alpha subunit of the insulin receptor activates the protein tyrosine kinase of the beta subunit, which then undergoes an autophosphorylation that increases its tyrosine kinase activity. Three adapter proteins, IRS1, IRS2 and Shc, become phosphorylated on tyrosine residues following insulin receptor activation. These three phosphorylated proteins then interact with SH2 domain containing signaling proteins.

NCBI and Uniprot Product Information

• NCBI GI #: 119395736
• NCBI GeneID: 3643
• NCBI Accession #: NP_000199.2
• NCBI GenBank Nucleotide #: NM_000208.2
• UniProt Accession #: P06213; Q17RW0; Q59H98; Q9UCB7; Q9UCB8; Q9UCB9
• Molecular Weight: 156,333 Da
• NCBI Official Full Name: insulin receptor isoform Long preproprotein
• NCBI Official Synonym Full Names: insulin receptor
• NCBI Official Symbol: INSR
• NCBI Official Synonym Symbols: HHF5; CD220
• NCBI Protein Information: insulin receptor; IR
• UniProt Protein Name: Insulin receptor
• Protein Family: Insulin receptor
• UniProt Gene Name: INSR
• UniProt Synonym Gene Names: IR
• UniProt Entry Name: INSR_HUMAN

NCBI Description

After removal of the precursor signal peptide, the insulin receptor precursor is post-translationally cleaved into two chains (alpha and beta) that are covalently linked. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Uniprot Description

INSR: a receptor tyrosine kinase that mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). The holoenzyme is cleaved into two chains, the alpha and beta subunits. The active complex is a tetramer containing 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains constitute the ligand- binding domain, while the beta chains carry the kinase domain. Interacts with SORBS1 but dissociates from it following insulin stimulation. Familial mutations associated with insulin resistant diabetes, acanthosis nigricans, pineal hyperplasia, and polycystic ovary syndrome. SNP variants may be associated with polycystic ovary syndrome, atypical migraine and diabetic hyperlipidemia. Mutations also cause leprechaunism, a severe insulin resistance syndrome causing growth retardation and death in early infancy. Two isoforms of the human protein are produced by alternative splicing. The Short isoform has a higher affinity for insulin than the longer. Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta. Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.

Protein type: EC 2.7.10.1; Membrane protein, integral; Protein kinase, TK; Kinase, protein; Protein kinase, tyrosine (receptor); TK group; InsR family

Chromosomal Location of Human Ortholog: 19p13.3-p13.2

Cellular Component: membrane; intracellular membrane-bound organelle; integral to plasma membrane; plasma membrane; endosome membrane; caveola; receptor complex

Molecular Function: insulin binding; insulin-like growth factor receptor binding; protein binding; insulin-like growth factor I binding; GTP binding; protein-tyrosine kinase activity; insulin receptor substrate binding; PTB domain binding; phosphoinositide 3-kinase binding; receptor signaling protein tyrosine kinase activity; insulin-like growth factor II binding; ATP binding; insulin receptor activity

Biological Process: heart morphogenesis; epidermis development; positive regulation of nitric oxide biosynthetic process; peptidyl-tyrosine phosphorylation; activation of MAPK activity; protein amino acid autophosphorylation; positive regulation of glycogen biosynthetic process; regulation of embryonic development; exocrine pancreas development; glucose homeostasis; positive regulation of glucose import; positive regulation of MAPKKK cascade; regulation of transcription, DNA-dependent; male sex determination; positive regulation of cell proliferation; protein heterotetramerization; positive regulation of developmental growth; positive regulation of mitosis; activation of protein kinase B; positive regulation of protein kinase B signaling cascade; G-protein coupled receptor protein signaling pathway; cellular response to insulin stimulus; carbohydrate metabolic process; positive regulation of glycolysis; insulin receptor signaling pathway; activation of protein kinase activity; positive regulation of protein amino acid phosphorylation; positive regulation of DNA replication; transformation of host cell by virus; positive regulation of cell migration

Disease: Diabetes Mellitus, Insulin-resistant, With Acanthosis Nigricans; Hyperinsulinemic Hypoglycemia, Familial, 5; Pineal Hyperplasia, Insulin-resistant Diabetes Mellitus, And Somatic Abnormalities; Donohue Syndrome