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  • Your Good Partner in Biology Research

    Recombinant Human Insulin receptor(INSR),Partial

    In Stock
    • 货号:
      CSB-EP011753HU
    • 规格:
      ¥10872
    • 图片:
      • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
    • 其他:

    产品详情

    • 纯度:
      Greater than 90% as determined by SDS-PAGE.
    • 基因名:
      INSR
    • Uniprot No.:
    • 别名:
      CD220; HHF5; human insulin receptor; Insr; INSR_HUMAN; Insulin receptor subunit beta; IR 1; IR; IR-1 ; IR1
    • 种属:
      Homo sapiens (Human)
    • 蛋白长度:
      Partial
    • 来源:
      E.coli
    • 分子量:
      47.2kDa
    • 表达区域:
      1023-1298aa
    • 氨基酸序列
      ITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSF
      Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
    • 蛋白标签:
      N-terminal 6xHis-SUMO-tagged
    • 产品提供形式:
      Liquid or Lyophilized powder
      Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
    • 缓冲液:
      Tris-based buffer,50% glycerol
    • 储存条件:
      Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
    • 保质期:
      The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
      Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
    • 货期:
      3-7 business days
    • 注意事项:
      Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
    • 产品描述:

      The recombinant Human INSR protein is encoded by the gene of INSR (1023-1298aa). The gene of INSR was cloned in a system (E.coli) that supported the expression of INSR and translation of messenger RNA. Modification of INSR by recombinant DNA technology could lead to the expression of the target protein. The protein was fused with N-terminal 6xHis-SUMO tag in the production. The purity is 90% determined by SDS-PAGE.

      INSR is a protein coding gene that encodes Insulin receptor. According to some studies, INSR may have the following features.
      A new type of single nucleotide polymorphism in the INSR gene of polycystic ovary syndrome. Restoring the insulin signal in the liver of Insr knockout mice cannot normalize the effect of liver insulin. The genetic variation of INSR exon 17 is related to insulin resistance and hyperandrogenemia in thin Indian women with polycystic ovary syndrome. The oncogenic functions of IGF1R and INSR in prostate cancer include enhancing tumor growth, cell migration and angiogenesis. Sequencing analysis of insulin receptor defects and detection of two new mutations in the INSR gene. Insulin receptor and kidney: renal cancer in patients with recessive INSR mutations.

    • Datasheet & COA:
      Please contact us to get it.

    产品评价

    靶点详情

    • 功能:
      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. In adipocytes, inhibits lipolysis.
    • 基因功能参考文献:
      1. The structural refinement of the antagonist once conjugated to insulin provided a set of partial agonists exhibiting between 25 and 70% of the maximal agonism of native insulin at the two insulin receptor isoforms, with only slight differences in inherent potency PMID: 29412818
      2. Cav-2beta isoform yielded by alternative translation initiation desensitizes insulin receptor (IR) via dephosphorylation by PTP1B, and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. PMID: 29604334
      3. They retained the main IGF-1R-related properties, but the hormones with His49 in IGF-1 and His48 in IGF-2 showed significantly higher affinities for IR-A and for IR-B, being the strongest IGF-1- and IGF-2-like binders of these receptors ever reported. PMID: 29608283
      4. MARCH1 ubiquitinates INSR to decrease cell surface INSR levels, but unlike other INSR ubiquitin ligases, MARCH1 acts in the basal state rather than after insulin stimulation. PMID: 27577745
      5. we aim to provide an overview of the physiological and pathophysiological roles of the IR within metabolic syndrome and its related pathologies, including cardiovascular health, gut microflora composition, gastrointestinal tract functioning, polycystic ovarian syndrome, pancreatic cancer, and neurodegenerative disorders PMID: 29462993
      6. In vitro results show that glycation of INSR decreases insulin binding under hyperglycemic conditions suggesting this mechanism may provide a mechanism by which INS resistance develops in diabetes. PMID: 29207492
      7. Circulating pri-miRNA-944 and 3662 can improve non-invasive non-small cell lung cancer detection of operable stages of SCC and AC PMID: 28964576
      8. current data demonstrate that both INSR and IGF1R are directly targeted by C-myc and exert similar effects to promote the tumorigenesis and metastasis of TSCC through the NF-kappaB pathway. PMID: 29518496
      9. the mechanism by which insulin induces IR translocation to the cell nucleus, was examined. PMID: 29317261
      10. We conclude that the crosstalk between angiotensin AT1 receptor and insulin receptor signaling shows a high degree of specificity, and involves Galphaq protein, and activation of distinct kinases. Thus, the BRET(2) technique can be used as a platform for studying molecular mechanisms of crosstalk between insulin receptor and 7TM receptors. PMID: 28854843
      11. INSR rs1051690 SNP is associated with increased risk of gastric cancer, while polymorphisms in IL12B, CCND1 and IL10 genes are not linked with the presence of gastric cancer PMID: 28596683
      12. Findings demonstrate that, in human breast cancer cells, DDR1 regulates IR expression and ligand dependent biological actions. This novel functional crosstalk is likely clinically relevant. PMID: 28591735
      13. in beta cells, INSR-B has a protective role, while INSR-A expression sensitizes beta cells to programmed cell death. PMID: 27526875
      14. These results support the hypothesis that INSR gene expression in different areas of Alzheimer's patient's brains. PMID: 28164769
      15. In endocrine-sensitive breast cancer cells, insulin was not growth stimulatory, likely due to the presence of hybrid InsR/IGF1R, which has high affinity for IGF-I, but not insulin. Combination inhibition of InsR and IGF1R showed complete suppression of the system in endocrine-sensitive breast cancer cells PMID: 28468775
      16. Report complex relationships between individual tumor-specific expression of IGF1R/pIGF1R and InsR/pInsR, response endocrine treatment and breast cancer prognosis. PMID: 28030849
      17. analysis of compounds that cause IGF-1Rbeta but not Insulin Receptor degradation specifically in tumor cells with no effects seen in normal diploid fibroblasts PMID: 27384680
      18. The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. PMID: 28707052
      19. The data in this paper demonstrate that IR knockdown in primary tumors partially reverses the growth-promoting effects of hyperinsulinemia as well as highlighting the importance of the insulin receptor signaling pathway in cancer progression, and more specifically in epithelial-mesenchymal transition. PMID: 27435064
      20. INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in epithelial ovarian cancer patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis. PMID: 28436941
      21. The IGF1R purified in n-dodecyl-beta-D-maltoside showed ligand-stimulated autophosphorylation and kinase activity, suggesting an intact transmembrane signaling mechanism. PMID: 28830678
      22. Signaling via the insulin (INS) and insulin-like growth factor 1 (IGF1) receptors (INSR and IGF1R) regulate basal cell (BC) differentiation into ciliated cells. PMID: 28050756
      23. High INSR expression is associated with drug Resistance in Gastrointestinal Stromal Tumors. PMID: 28760855
      24. the above data indicate a direct role for IR expression as a determinant of PT-gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. PMID: 27322100
      25. Activation of D4 receptor inhibits insulin receptor expression in RPT cells from WKY rats. The aberrant inhibition of D4 receptor on insulin receptor expression and effect might be involved in the pathogenesis of essential hypertension. PMID: 27107134
      26. The HIR MAb binds the insulin receptor on the BBB. PMID: 28279069
      27. data indicate that post-receptor signalling abnormalities might contribute to Myotonic dystrophy insulin resistance regardless the alteration of INSR splicing. PMID: 28915272
      28. We identified vascular INSR expression as a potential biomarker for progression in bladder cancer. The data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. PMID: 28295307
      29. The INSR rs2059806 SNP is associated with pre-eclampsia phenotypes in two independent cohorts suggesting that genetic susceptibility may be implicated in the link between pre-eclampsia and subsequent vascular and metabolic diseases. PMID: 28117222
      30. IGF2 and insulin receptor A are important for uterine leiomyoma stem cell proliferation and may represent paracrine signaling between leiomyoma cell types. PMID: 28324020
      31. Disruption of insulin receptor function inhibits proliferation in endocrine-resistant breast cancer cells PMID: 26876199
      32. Differential IR isoform expression suggests a distinct role for each in endometrial physiology and cancer. PMID: 27088794
      33. Results show that IR expression level in renal cell carcinoma tissue was significantly lower in patients with tumor stage pT2-4 and/or distant metastases. PMID: 28393204
      34. Findings suggest that the induction of microRNA miR-1271 by saturated fatty acid palmitate promotes the development of insulin resistance by targeting insulin receptor (INSR) and insulin receptor substrate 1 protein (IRS-1) in hepatocytes. PMID: 27613089
      35. Study reveals an important function of CHIP-mediated proteolysis in insulin and IGF1 signaling; upon proteotoxic stress conditions and during aging, CHIP is recruited toward disposal of misfolded proteins, reducing its capacity to degrade the INSR; identify a degradation pathway that controls the level of active DAF-2/INSR in C. elegans, Drosophila and human cells. PMID: 28431247
      36. EGF and insulin receptor tyrosine kinase exemplify how receptor location is coupled to signal transduction. (Review) PMID: 27023845
      37. a straightforward protocol for production of recombinant IGF-II and prepared six IGF-II analogs with IGF-I-like mutations. All modified molecules exhibit significantly reduced affinity toward IR-A, particularly the analogs with a Pro-Gln insertion in the C-domain. Moreover, one of the analogs has enhanced binding affinity for IGF-1R due to a synergistic effect of the Pro-Gln insertion and S29N point mutation. PMID: 27510031
      38. Conus geographus G1 (Con-Ins G1), is the smallest known insulin found in nature and lacks the C-terminal segment of the B chain that, in human insulin, mediates engagement of the insulin receptor and assembly of the hormone's hexameric storage form. This study found that Con-Ins G1 is monomeric, strongly binds the human insulin receptor and activates receptor signaling. PMID: 27617429
      39. Mutations of the INSR gene is associated with acanthosis nigricans and hyperandrogenism. PMID: 27505086
      40. Identification of a Novel Homozygous INSR Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates. PMID: 27326825
      41. Findings suggest that insulin receptor substrate -1 Gly972Arg polymorphism is associated with polycystic ovary syndrome in the Caucasian ethnicity, and insulin receptor substrate -2 Gly1057Asp polymorphism is correlated with polycystic ovary syndrome in the Asian ethnicity. However, insulin receptor His 1058 C/T polymorphism may not be implicated in polycystic ovary syndrome. PMID: 27098445
      42. Two miR-binding SNPs SLC30A8 rs2466293 and INSR rs1366600 increased Gestational diabetes mellitus susceptibility. Functional studies were required to confirm the underlying mechanism. PMID: 28190110
      43. The data demonstrate that insulin, IGF1 and IGF2 elicit different insulin receptor phosphorylation kinetics and potencies that translate to downstream signaling. PMID: 27155325
      44. Suggest a novel role of miR-503 as a regulator of vascular smooth muscle cell proliferation and migration by modulating INSR. PMID: 27829550
      45. In silico characterization of nsSNPs affecting INSR gene function can aid in better understanding of genetic differences in disease susceptibility. PMID: 27840822
      46. The INSR gene is potentially associated with eating difficulties in preterm infants. PMID: 26629831
      47. four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR PMID: 27034931
      48. Study describes a revised structure of the human insulin receptor ectodomain revealing new features within the receptor insert domain and corrects errors in the first and third fibronectin type III domains. The new structure allows improved resolution of the insert domain, a critical element to ligand binding and signal transduction. PMID: 26853939
      49. C1008T SNP at exon 17 of INSR is associated with insulin resistance in Indian women with polycystic ovarian syndrome. PMID: 26721804
      50. A novel insertion/deletion (indel) mutation was found in INSR gene. PMID: 26874853

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    • 相关疾病:
      Rabson-Mendenhall syndrome (RMS); Leprechaunism (LEPRCH); Diabetes mellitus, non-insulin-dependent (NIDDM); Familial hyperinsulinemic hypoglycemia 5 (HHF5); Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A)
    • 亚细胞定位:
      Cell membrane; Single-pass type I membrane protein. Late endosome. Lysosome.
    • 蛋白家族:
      Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily
    • 组织特异性:
      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 vasc
    • 数据库链接:

      HGNC: 6091

      OMIM: 125853

      KEGG: hsa:3643

      STRING: 9606.ENSP00000303830

      UniGene: Hs.465744



    1v1周青梅郑宣木天寥
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