Anti-IGF2R Antibody Picoband® (monoclonal, 6G2)

Insulin-like growth factor 2 receptor, also called IGF2R or I-MPR is a protein that in humans is encoded by the IGF2R gene. This gene is mapped to 6q25.3. This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate, although the binding sites for either are located on different segments of the receptor. This receptor functions in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. While the related mouse gene shows exclusive expression from the maternal allele, imprinting of the human gene appears to be polymorphic, with only a minority of individuals showing expression from the maternal allele.

Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP- bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:26865365, PubMed:24318877) . Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256) . Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183) . Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385) . Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223) . Negatively regulates heat shock- induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401) .

1. Killian, J. K., Oka, Y., Jang, H.-S., Fu, X., Waterland, R. A., Sohda, T., Sakaguchi, S., Jirtle, R. L. Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations. Hum. Mutat. 18: 25-31, 2001. 2. Latos, P. A., Pauler, F. M., Koerner, M. V., Senergin, H. B., Hudson, Q. J., Stocsits, R. R., Allhoff, W., Stricker, S. H., Klement, R. M., Warczok, K. E., Aumayr, K., Pasierbek, P., Barlow, D. P. Airn transcriptional overlap, but not its IncRNA products, induces imprinted Igf2r silencing. Science 338: 1469-1472, 2012.

Store at -20°C for one year from date of receipt. After reconstitution, at 4°C for one month. It can also be aliquotted and stored frozen at -20°C for six months. Avoid repeated freeze-thaw cycles.