Recombinant Human IA2 Protein (80AA& 94AA, N-6His)

Name: Recombinant Human IA2 Protein (80AA& 94AA, N-6His)
Brand: Beta LifeScience
SKU: BL-1574NP
Availability: InStock

BL-1574NP: Greater than 90% as determined by reducing SDS-PAGE. (QC verified)

Collections: Other recombinant proteins, Recombinant proteins

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Product Overview

Description	Recombinant Human Islet Cell Antigen 2/Protein Tyrosine Phosphatase Receptor-type N is produced by our E.coli expression system and the target gene encoding Gln607-Asn686&Trp795-Leu888 is expressed with a 6His tag at the N-terminus.
Accession	Q16849
Synonym	Receptor-type tyrosine-protein phosphatase-like N; R-PTP-N; Islet cell antigen 512; ICA 512; Islet cell autoantigen 3; PTP IA-2; PTPRN; ICA3; ICA512
Gene Background	Receptor-type tyrosine-protein phosphatase-like N (PTPRN) belongs to the protein-tyrosine phosphatase family and receptor class 8 subfamily. PTPRN contains 1 tyrosine-protein phosphatase domain, is expressed in neuroendocrine cells only. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. It implicated in neuroendocrine secretory processes. It may be involved in processes specific for neurosecretory granules, such as their biogenesis, trafficking or regulated exocytosis or may have a general role in neuroendocrine functions. It seems to lack intrinsic enzyme activity, may play a role in the regulation of secretory granules via its interaction with SNTB2. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus.
Molecular Mass	22.9 KDa
Apmol Mass	26-30 KDa, reducing conditions
Formulation	Supplied as a 0.2 μm filtered solution of 20mM Tris-HCl, 150mM NaCl, 1mM DTT, 1mM EDTA, pH 8.0.
Endotoxin	Less than 0.1 ng/µg (1 EU/µg) as determined by LAL test.
Purity	Greater than 90% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity	Not tested
Reconstitution
Storage	Store at ≤-70°C, stable for 6 months after receipt. Store at ≤-70°C, stable for 3 months under sterile conditions after opening. Please minimize freeze-thaw cycles.
Shipping	The product is shipped on dry ice/polar packs. Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

Target Details

Target Function	Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Required to maintain normal levels of renin expression and renin release. Seems to lack intrinsic enzyme activity. May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization.; ICA512-TMF regulates dynamics and exocytosis of insulin secretory granules (SGs); binding of ICA512-TMF to SNTB2/beta-2-syntrophin is proposed to restrain SGs mobility and exocytosis by tethering them to the actin cytoskeleton depending on UTRN; the function is inhibited by cytoplasmic ICA512-CFF dimerizing with ICA512-TMF and displacing SNTB2.; ICA512-CCF translocated to the nucleus promotes expression of insulin and other granule-related genes; the function implicates binding to and regulating activity of STAT5B probably by preventing its dephosphorylation and potentially by inducing its sumoylation by recruiting PIAS4. Enhances pancreatic beta-cell proliferation by converging with signaling by STAT5B and STAT3. ICA512-CCF located in the cytoplasm regulates dynamics and exocytosis of insulin secretory granules (SGs) by dimerizing with ICA512-TMF and displacing SNTB2 thus enhancing SGs mobility and exocytosis.
Subcellular Location	Membrane; Single-pass type I membrane protein. Cytoplasmic vesicle, secretory vesicle membrane; Single-pass type I membrane protein. Perikaryon. Cell projection, axon. Cell junction, synapse. Cell membrane; Single-pass type I membrane protein. Endosome.; [ICA512-transmembrane fragment]: Cytoplasmic vesicle, secretory vesicle membrane.; [ICA512-cleaved cytosolic fragment]: Nucleus.
Protein Families	Protein-tyrosine phosphatase family, Receptor class 8 subfamily
Database References	HGNC: 9676 OMIM: 601773 KEGG: hsa:5798 STRING: 9606.ENSP00000295718 UniGene: Hs.89655
Associated Diseases	Autoantigen in insulin-dependent diabetes mellitus (IDDM).
Tissue Specificity	Expression is restricted to neuroendocrine cells. Found in pancreas, brain and pituitary.

Gene Functions References

E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories. PMID: 27881117
Identification of amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity. PMID: 26564179
RESP18HD is required for efficient sorting of ICA512 to secretory granules: RESP18HD is a key determinant for ICA512 granule targeting. PMID: 26836020
The binding of CREB to the promoter region, -216 to +115, enhanced IA-2 transcription by more than fivefold. PMID: 25528004
Kaplan-Meier survival curves estimated a worst pancreas graft survival for patients with positive IA-2 antibodies versus those patients with negative auto-antibodies and GAD65+ auto-antibodies after simultaneous pancreas kidney transplantation. PMID: 25645784
Humoral responses to islet antigen-2 and zinc transporter 8 are attenuated in patients carrying HLA-A*24 alleles at the onset of type 1 diabetes. PMID: 23396399
identification of cysteines that are critical for IA-2A binding of autoantibodies in patients with newly diagnosed type 1 diabetes PMID: 22966073
the IA-2A autoantibody response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development PMID: 23110943
Letter: report lack of anti-IA2 autoantibodies in primary antiphospholipid syndrome. PMID: 21442164
analysis of protein-protein interactions in crystals of the human receptor-type protein tyrosine phosphatase ICA512 ectodomain PMID: 21935384
ZnT8A, GADA and IA-2A are autoantibodies that may have a role in successful pancreas graft survival PMID: 21792090
In families with type 1 diabetes, there was a female predominance and more family history of associated autoimmune diseases (AAIDs) in the group with AAIDs, and less frequent anti-IA-2 antibodies PMID: 21744463
Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). PMID: 21577013
Studies indicate that T1DM can be detected by determining four autoantibodies, namely those antibodies against insulin, glutamic acid decarboxylase 65, insulinoma antigen (IA)-2 (ICA512) and the zinc transporter ZnT8. PMID: 21073664
Risk of autoantibody seroconversion among children followed in DPT-1 is age dependent PMID: 21270193
Data show that significantly increased expression of MCP-1, IL-2 and PTPR-N was observed in Tourette's syndrome cases. PMID: 20193755
T cells stimulated in vitro by the IA-2 epitope express IFN-gamma when restimulated by the similar rotavirus VP7 peptide. PMID: 20083660
Report a chimeric assay providing an efficient and economical technique to screen for islet autoantibodies reacting with IA-2 and ZnT8 in type 1 diabetes mellitus. PMID: 20035758
ICA512(IA-2) epitope specific assays distinguish transient from diabetes associated autoantibodies. PMID: 11908951
Autoantibodies to IA-2 in type 1 diabetes: measurements with a new enzyme-linked immunosorbent assay. PMID: 12021115
BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. PMID: 12021127
findings indicate that glutamine at position 862, and residues 876-880 of the WPD loop of IA-2 are important for several of the IA-2 specific PTP domain epitopes PMID: 14624760
The islet cell autoantigen 512 (ICA512)/IA-2 is a receptor tyrosine phosphatase-like protein associated with the insulin secretory granules (SGs) of pancreatic beta-cells. PMID: 15596545
Measuring IA-2A is useful for the diagnosis and prognosis of type 1 diabetes in Japanese. PMID: 15620435
IA-2 is an important regulator of dense core vesicle number and glucose-induced and basal insulin secretion in beta cells. PMID: 15939893
identification of proteins that interact with IA-2, the IA-2 interactome; the IA-2 interactome based on pull-down experiments, currently consists of 12 proteins; identification of these interacting proteins provides clues as to how IA-2 functions PMID: 16273344
Autoantibodies in type 1 diabetes for this protein provide a model for other autoimmune diseases. PMID: 18373080
HLA class II alleles strongly influence the prevalence of IA-2A in type 1 diabetes. PMID: 18504544
Inexpensive, nonradioactive method for the detection of autoantibodies cell-prepared PTPRN (also known as IA-2) in diabetics. PMID: 18535195
The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant. PMID: 19447008

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