Immunofluorescence staining of HepG2 cells with CSB-PA019036LA01HU at 1:266, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeabilized using 0.2% Triton X-100 and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4°C. The secondary antibody was Alexa Fluor 488-congugated AffiniPure Goat Anti-Rabbit IgG(H+L).
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Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2. Positively regulates toll-like receptor (TLR)-induced type 1 interferon production. Promotes host antiviral responses mediated by type 1 interferon. Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy. Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide).
基因功能參考文獻(xiàn):
A significant association was detected between the variant genotype of the PTPN22 gene (C1858T, rs2476601) and T1DM in Kuwaiti Arabs. HLA-DQ2 and DQ8 alleles showed a strong association with T1DM. Of T1DM patients having the variant TT-genotype of the PTPN22 gene, 93% had at least one DQ2 allele and 60% had either a DQ2 or a DQ8 allele. TT homozygotes had either DR3-DRB5 or DRB3-DRB4 genotypes. PMID: 29924845
PTPN22 and CTLA-4 polymorphisms are associated with Autoimmune polyglandular syndromes and differentiate between polyglandular and monoglandular autoimmunity. PMID: 29409002
gene expression levels of PTPN22 were higher in the alopecia areata patients in Iranian population; association between the PTPN22 genetic variation was not confirmed by this study PMID: 29979892
The data presented here suggests that the T allele of PTPN-22 C1858T polymorphism might be a risk factor for T1D development in Saudi children. PMID: 29611765
The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. PMID: 29895027
The PTPN22 G788A polymorphism confers protection against systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis. (Meta-analysis) PMID: 29729713
Data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in Crohn's disease patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria. PMID: 29456405
the R620W PTPN22 variant seems to be a major risk factor for anti-neutrophil cytoplasmic antibody-associated vasculitis. PMID: 27686100
We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15x10-5, OR=5.07), rs16861329 on 3q27.3 (P=2.02x10-4, OR=0.87) and rs849135 on 7p15.1 (P=6.59x10-9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. PMID: 28603863
The frequency of STAT4 variant allele was significantly higher in rheumatoid arthritis (RA) patients than in controls, while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The study also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients. PMID: 28424905
c.1858CC genotype associated with a beneficial functional effect on residual insulin secretion and HbA1c level dynamics in type 1 diabetes PMID: 27615679
present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858 C > T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858 C > T as a potential genetic marker in SLE susceptibility. PMID: 28990435
There were no significant relationships with PTPN22 SNPs in primary biliary cholangitis (PBC) patients. Interestingly, the AAGTCCC haplotype was significantly associated with resistance to both Autoimmune hepatitis (odds ratio [OR] = 0.58, P = 0.0067) and PBC (OR = 0.58, P = 0.0048). SNPs in the PTPN22 gene may therefore play key roles in the genetic resistance to autoimmune liver disease in the Japanese. PMID: 27406031
Studied association of and RNASET2, GPR174, and PTPN22 gene polymorphisms and liver damage(LD) due to Graves' disease (GD) hyperthyroidism. Found GPR174 rs3827440, PTPN22 rs3789604, and RNASET2 rs9355610 were significantly associated with altered GD-derived LD risk. PMID: 28568286
PTPN22 is hypermethylated in esophageal squamous cell carcinoma PMID: 27613842
A higher prevalence of homozygous PTPN22 -1123CC genotype was found in controls than in rheumatoid arthritis (RA) patients, suggesting a potential protective effect against RA. Concerning anti-cyclic citrullinated protein antibodies levels, the CC genotype carriers showed the lowest median levels in RA. PMID: 28291534
Our data provide the first demonstration that PTPN22 R620W confers Graves Disease susceptibility among Latin-American patients. PMID: 28500376
The GG genotype of PTPN22 rs6665194 (-3508A>G) is associated with significantly reduced risk of Rheumatoid Arthritis in Asians. PMID: 28653215
PTPN22 rs2476601 was related to systemic lupus erythematosus in Americans, Europeans, and Africans.[meta-analysis] PMID: 28528372
the rs1310182 SNP of the PTPN22 gene may be a predisposing factor of celiac disease in the Iranian population PMID: 28481156
PTPN22 polymorphisms may have a role in risk of ankylosing spondylilitis [meta-analysis] PMID: 28555069
Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease. PMID: 28627089
Our study supports an association between the PTPN22 gene polymorphism rs2476601 and an increased risk for Type 1 diabetes in children PMID: 29408732
PTPN22 single nucleotide polymorphism is associated with type 1 diabetes in Iran PMID: 28375784
Relationship with insulin-dependent diabetes mellitus was found only in polymorphism R620W PMID: 29099700
PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). PMID: 27703032
collective murine and human data provide an alternative model for how the PTPN22 C1858T variant promotes self-reactivity into the naive B cell repertoire and, consequently, is likely to increase the probability of triggering autoimmune B cell responses in at-risk individuals PMID: 28801357
The associations observed between PTPN22 (C1858T) and the risk of endometriosis suggest this polymorphism might be a useful susceptibility marker for this disease. PMID: 28444099
PTPN22 deficiency resulted in pronounced colitis, increased NLRP3 phosphorylation, but reduced levels of mature IL-1beta. PMID: 27043286
the coding regions of 17 genes involved in the regulation of the immune response were determined by massive parallel sequencing. The analysis revealed 39 nonsynonymous SNPs that lead to amino acid substitutions, including the following informative genetic markers: PTPN22 c.1858C>T (rs2476601), TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791), IL7R c.197T>C (rs1494555) and IL7R c.412G>A (rs1494558). PMID: 28537236
PTPN22 variants are associated with ANCA-associated vasculitis risk. PMID: 28029757
C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 characterizes a subset of type 1 diabetic patients with higher levels of C-peptide at diagnosis and lower insulin requirement at 6 months from diagnosis. PMID: 26902538
The presence of PTPN22 1858C-->T polymorphism with HLA shared epitope and autoantibodies increases risk of rheumaotid arthritis development and erosive disease. PMID: 27324632
for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients PMID: 27467733
A significant association was found between the rs2476601 polymorphism of the PTPN22 gene and cystic fibrosis in Mexican patients PMID: 27751376
The PTPN22 R620W minor allele frequency was increased in IIM patients (50 of 398, 12.6%) compared with controls. PMID: 27312665
This study reveals a significant association between SNPs in PTPN22, CTLA-4 gene and AR with asthma in Chinese Han children, which might be susceptibility factors for Allergic rhinitis and asthma. PMID: 27917628
The association of PTPN22 variant, R620W (LypW), with defects in trivalent influenza vaccine-induced CD4(+) T-cell expansion and antibody affinity maturation suggests that LypW may predispose individuals to have a diminished capacity to generate protective immunity against influenza virus. PMID: 27034343
PTPN22 + 1858 T allele predisposes European individuals to vitiligo. PMID: 28164884
PTPN22W* risk variant increases susceptibility for primary Sjogren's Syndrome, particularly the low type I IFN subset implying the presence of distinct genetic backgrounds among low and high type I IFN autoimmune subgroups PMID: 27810512
These data support that PTPN22 1858C/T, PTPRJ 2965C/G and 1176 A/C polymorphisms and ACP1 A, B and C alleles are not associated with a higher risk of immune thrombocytopenia P in adults. PMID: 27309885
this study reveals that the +1858T allele in the PTPN22 gene is associated with Rheumatoid Arthritis and Celiac Disease in a population from the south-west of Iran. PMID: 27215233
PTPN22 Gene Polymorphism rs1310182 has a role in juvenile idiopathic arthritis PMID: 27732119
The functional PTPN22 C1858T polymorphism was associated with an increased risk for Rheumatoid arthritis in the Mexican population. PMID: 26951256
this study shows that PTPN22 contributes to rheumatoid arthritis susceptibility in Egyptians PMID: 27125674
this study shows that PTPN22 gene polymorphism is associated wit the risk of allergic rhinitis in China PMID: 27888068
this study shows that PTPN22 polymorphism is associated with susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura PMID: 27866840
In conclusion, the authors found a lack of association of PTPN22 -1123G>C and +1858C>T polymorphisms with the risk of developing systemic lupus erythematosus in a Mexican population. PMID: 26013387
this study shows that PTPN22 genetic polymorphisms play role in predisposition of type 1 diabetes mellitus in Egyptian children PMID: 27288719
Results do not support a major role of PTPN22 gene SNPs in Behcet's disease in Spanish population. PMID: 27050764
Protein-tyrosine phosphatase family, Non-receptor class 4 subfamily
組織特異性:
Expressed in bone marrow, B and T-cells, PBMCs, natural killer cells, monocytes, dendritic cells and neutrophils. Both isoform 1 and 4 are predominantly expressed in lymphoid tissues and cells. Isoform 1 is expressed in thymocytes and both mature B and T-