Human Recombinant INSR
Reference ID:KB-2307
Western Blot
Flow Cytometry
Gene of Interest
Gene Synonyms:INSR
Protein Names:Insulin receptor (IR) (EC (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
Accession Data
Organism:Homo sapiens (Human)
Mass (kDa):1563.33
Length (aa):1382
Proteomics (Proteome ID):UP000005640
Proteomics (Chromosome): Chromosome 19
Active Site:ACT_SITE 1159 1159 Proton donor/acceptor. {ECO:0000269|PubMed:9312016}.
Activity Regulation: Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates. {ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:11598120, ECO:0000269|PubMed:11726652, ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:2211730}.
Binding Site:BINDING 1033 1033 ATP. {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:18278056}.; BINDING 1057 1057 ATP. {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:18278056}.; BINDING 1177 1177 ATP. {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:18278056}.
Catalytic Activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:11124964, ECO:0000269|PubMed:11598120, ECO:0000269|PubMed:12707268, ECO:0000269|PubMed:18278056, ECO:0000269|PubMed:19056263, ECO:0000269|PubMed:19071018, ECO:0000269|PubMed:19394223, ECO:0000269|PubMed:9312016};
Function [CC]: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. PubMed:12138094 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, PubMed:16831875 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. {ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}.
Nucleotide Binding:NP_BIND 1104 1110 ATP. {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:18278056}.; NP_BIND 1163 1164 ATP. {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:18278056}.
Site:SITE 66 66 Insulin-binding. {ECO:0000305}.
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. {ECO:0000269|PubMed:10207053, ECO:0000269|PubMed:2369896, ECO:0000269|PubMed:9202395, ECO:0000269|PubMed:9355755}.
Chemical Profile | ChEBI:H(+) [CHEBI:15378]; ATP [CHEBI:30616]; L-tyrosine residue [CHEBI:46858]; L-tyrosine-phosphate residue [CHEBI:82620]; ADP [CHEBI:456216]
ChEBI (Catalytic Activity):H(+) [CHEBI:15378]; ATP [CHEBI:30616]; L-tyrosine residue [CHEBI:46858]; L-tyrosine-phosphate residue [CHEBI:82620]; ADP [CHEBI:456216]
Disease:Rabson-Mendenhall syndrome (RMS) [MIM:262190]: Severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive. {ECO:0000269|PubMed:10443650, ECO:0000269|PubMed:12023989, ECO:0000269|PubMed:17201797, ECO:0000269|PubMed:2121734, ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:8314008}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Leprechaunism (LEPRCH) [MIM:246200]: Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive. {ECO:0000269|PubMed:12023989, ECO:0000269|PubMed:12538626, ECO:0000269|PubMed:12970295, ECO:0000269|PubMed:1607067, ECO:0000269|PubMed:1730625, ECO:0000269|PubMed:22768670, ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:24498630, ECO:0000269|PubMed:2479553, ECO:0000269|PubMed:2834824, ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:7538143, ECO:0000269|PubMed:7815442, ECO:0000269|PubMed:8188715, ECO:0000269|PubMed:8326490, ECO:0000269|PubMed:8419945, ECO:0000269|PubMed:8636294, ECO:0000269|PubMed:9249867, ECO:0000269|PubMed:9299395, ECO:0000269|PubMed:9703342}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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. {ECO:0000269|PubMed:1470163, ECO:0000269|PubMed:1607076, ECO:0000269|PubMed:7657032}. Note=The gene represented in this entry may be involved in disease pathogenesis.; Familial hyperinsulinemic hypoglycemia 5 (HHF5) [MIM:609968]: Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. {ECO:0000269|PubMed:15161766}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]: Characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor. {ECO:0000269|PubMed:10733238, ECO:0000269|PubMed:11260230, ECO:0000269|PubMed:12107746, ECO:0000269|PubMed:12970295, ECO:0000269|PubMed:1563582, ECO:0000269|PubMed:1963473, ECO:0000269|PubMed:2002058, ECO:0000269|PubMed:2168397, ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:2544998, ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:3283938, ECO:0000269|PubMed:8243830, ECO:0000269|PubMed:8288049, ECO:0000269|PubMed:8314008, ECO:0000269|PubMed:8388389, ECO:0000269|PubMed:9175790}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Mutagenesis:MUTAGEN 991 991 L->A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. {ECO:0000269|PubMed:7559478}.; MUTAGEN 992 992 Y->A: Reduces interaction with IRS1 but has no effect on interaction with SHC1. {ECO:0000269|PubMed:7559478}.; MUTAGEN 996 997 NP->AA: Abolishes interaction with IRS1. Severely disrupts, but does not abolish interaction with SHC1. {ECO:0000269|PubMed:7559478}.; MUTAGEN 996 996 N->A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. {ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7559478}.; MUTAGEN 997 997 P->A: Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1. {ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7559478}.; MUTAGEN 998 998 E->A: Does not affect interaction with IRS1, SHC1 or PIK3R1. {ECO:0000269|PubMed:7537849}.; MUTAGEN 999 999 Y->E: Abolishes interaction with IRS1 and SHC1. {ECO:0000269|PubMed:2842060, ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7559478, ECO:0000269|PubMed:9428692}.; MUTAGEN 999 999 Y->F: Has no effect on insulin-stimulated autophosphorylation, but inhibits the biological activity of the receptor. Abolishes interaction with IRS1 and almost completely prevents interaction with SHC1. Has no effect on interaction with PIK3R1. Abolishes interaction with STAT5B. {ECO:0000269|PubMed:2842060, ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7559478, ECO:0000269|PubMed:9428692}.; MUTAGEN 1000 1000 L->A,R: Severely reduces interaction with SHC1. Has no effect on interaction with IRS1. {ECO:0000269|PubMed:7559478}.; MUTAGEN 1002 1002 A->D: Reduces interaction with IRS1 but has no effect on interaction with SHC1. {ECO:0000269|PubMed:7559478}.; MUTAGEN 1011 1011 Y->A: Increases kinase activity. {ECO:0000269|PubMed:12707268}.; MUTAGEN 1057 1057 K->A: Abolishes the kinase activity and abolishes interaction with IRS1, SHC1, GRB7 and PIK3R1. {ECO:0000269|PubMed:10803466, ECO:0000269|PubMed:3101064, ECO:0000269|PubMed:7537849}.; MUTAGEN 1057 1057 K->M,R: Abolishes the kinase activity. {ECO:0000269|PubMed:10803466, ECO:0000269|PubMed:3101064, ECO:0000269|PubMed:7537849}.; MUTAGEN 1159 1159 D->N: Loss of kinase activity. {ECO:0000269|PubMed:11598120}.; MUTAGEN 1163 1163 R->Q: Loss of kinase activity. {ECO:0000269|PubMed:11598120}.; MUTAGEN 1189 1189 Y->F: Reduced interaction with GRB7. {ECO:0000269|PubMed:10803466}.; MUTAGEN 1190 1190 Y->F: Strongly reduced interaction with GRB7. {ECO:0000269|PubMed:10803466}.
Reagent Data
Molecular Weight:5.807
Measured:? 550 IU/mg
Determined By:Assay (Variable)
Assay Profile:substrate: dermatan sulfate
Formulation:Sterile-filtered colorless solution
Formulation Concentration:1 mg/ml
Buffer Volume:Standard
Buffer Solution:PBS
Purity:> 98%
Determined: SDS-PAGE
Sample Handling
Stability:This bioreagent is stable at 4°C (short-term) and -70°C(long-term). After reconstitution, sample may be stored at 4°C for 2-7 days and below -18°C for future use.
Preparation:Reconstitute in sterile distilled H2O to no less than 100 ug/ml; dilute reconstituted stock further in other aqueous solutions if needed. Please review COA for lot-specific instructions. Final measurements should be determined by the end-user for optimal performance.