Recombinant Human CTLA-4 Protein (C-6His)

Name: Recombinant Human CTLA-4 Protein (C-6His)
Brand: Beta LifeScience
SKU: BL-0320NP
Availability: InStock

BL-0320NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Collections: All products, Antibody / cell therapy targets, Antibody therapeutic / adc target proteins, Co-inhibitory receptors, Featured immune checkpoint protein molecules, High-quality recombinant proteins, Immune checkpoint proteins

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Product Overview

Description	Recombinant Human Cytotoxic T-lymphocyte Protein 4 is produced by our Mammalian expression system and the target gene encoding Lys36-Asp161 is expressed with a 6His tag at the C-terminus.
Accession	P16410
Synonym	Cytotoxic T-lymphocyte protein 4; Cytotoxic T-lymphocyte-associated antigen 4; CTLA-4; CD152; CTLA4
Gene Background	Cytotoxic Tlymphocyte 4(CTLA-4,CD152), is a type I transmembrane T cell inhibitory molecule that is a member of the Ig superfamily. Human or mouse CTLA4 cDNA encodes 223 amino acids (aa) including a 35 aa signal sequence, a 126 aa extracellular domain (ECD) with one Ig-like V-type domain, a 21 aa transmembrane (TM) sequence, and a 41 aa cytoplasmic sequence.It is widely expressed with highest levels in lymphoid tissues. CD28 and CTLA-4, together with their ligands, B7-1 and B7-2, constitute one of the dominant costimulatory pathways that regulate T and B cell responses. CD28 and CTLA-4 are structurally homologous molecules that are members of the immunoglobulin (Ig) gene superfamily. CTLA4 transmits an inhibitory signal to T cells, whereas CD28 transmits a stimulatory signal. Intracellular CTLA4 is also found in regulatory T Cells and may play an important role in their functions. Tcell activation through the Tcell receptor and CD28 leads to increased expression of CTLA4.
Molecular Mass	14.3 KDa
Apmol Mass	20-25 KDa, reducing conditions
Formulation	Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.
Endotoxin	Less than 0.1 ng/µg (1 EU/µg) as determined by LAL test.
Purity	Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity	Not tested
Reconstitution	Always centrifuge tubes before opening. Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles.
Storage	Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.
Shipping	The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

Target Details

Target Function	Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.
Subcellular Location	Cell membrane; Single-pass type I membrane protein. Note=Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalization.
Database References	HGNC: 2505 OMIM: 109100 KEGG: hsa:1493 STRING: 9606.ENSP00000303939 UniGene: PMID: 29409002 CTLA4 expression levels was found significantly lower in the alopecia areata patients in Iranian cohort; no association between CTLA4 genetic polymorphism and susceptibility to alopecia areata PMID: 29979892 The CTLA-4 gene +49 A/G polymorphism and the NOD2/CARD15 gene N852S polymorphism were not associated with CD or UC in a Turkish population PMID: 30213296 The CTLA4 gene is suggested to correlate with immune thrombocytopenia through its abnormal expression level instead of gene site mutation. PMID: 30319055 Paget disease is characterized by an intense lymphocytic response, devoid of the immune-suppressive impact of the PD-L1 pathway, but with occasional CTLA-4 expression PMID: 29943071 Depending on the environmental conditions, Mesenchymal stem/stromal cells express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, the immunosuppressive function of Mesenchymal stem/stromal cells is mediated mainly by the secretion of CTLA-4. PMID: 30087255 Increased frequency and CTLA-4-expression of Varicella Zoster Virus-specific T cells from cerebrospinal fluid or blood are specifically found in patients with Varicella Zoster Virus-related Central Nervous System-infection. PMID: 28845512 Rs56102377 in the 3'-UTR of CTLA4 may act as a protective factor by disrupting the regulatory role of miR-105 in CTLA4 expression. PMID: 30355938 The present work showed in West Algerian population that the HLA-B27 antigen and the variation in the CTLA4 3'UTR region played an important role in the ankylosing spondylitis susceptibility. The heterogeneity of this disease is deduced by genetic difference found between B27+ and B27- groups. PMID: 29675891 High CTLA4 expression is associated with Melanoma. PMID: 29150430 CTLA4 protein had significantly higher serum level in recurrent spontaneous abortion patients than in healthy controls. In recurrent spontaneous abortion patients, AA genotype carriers had higher CTLA4 serum level than that GG genotype carriers. Minor alleles of CTLA4 polymorphisms might inhibit the recurrent spontaneous abortion susceptibility via upregulated the protein expression level. PMID: 30334961 The results in our meta-analysis indicated that CTLA4 +49A/GG allele/AA genotype was associated with the risk of colorectal cancer in the Asian population and overall populations PMID: 29970719 The CTLA4 -318/C/T SNP was associated with an increased risk to develop IgAN, while the CT60 G/A genotype significantly associated with the risk for higher proteinuria PMID: 29539619 This review summarizes the current literature relevant to T cell exhaustion in patients with Hepatitis B virus (HBV)related chronic hepatitis, and discusses the roles of CTLA4 in T cell exhaustion. [review] PMID: 29786112 Study provides evidence that CTLA4 +49 A/G (Thr/Ala) polymorphism was strongly associated with T1diabetes in south India. PMID: 29603038 gene polymorphism is associated with psoriasis in Turkish population PMID: 29850619 The mRNA expression of FAS was lower in patients with TP53 mutation than TP53 wild-type. Our findings suggest that TP53 mutation is a potential negative predictor of metastatic melanoma treated with CTLA-4 blockade. PMID: 29793878 TSA results indicated that CTLA-4 +49A/G should be considered as a biomarker for HT, whereas both the CT60 and -318C/T SNPs warrant confirmation by further studies PMID: 29461867 susceptibility to RSA was subject to the synthetic regulation of chromosomal aberrations and genetic mutations within CLTA-4 and Foxp3, suggesting that the conduction of karyotype analysis and genetic detection for RSA patients could effectively guide effective RSA counseling and sound child rearing. PMID: 29476189 CTLA4 missense variant significantly associates with inhibitor development in Argentine patients with severe haemophilia A PMID: 28220572 Study suggests that miR-487a-3p might repress CTLA4 and FOXO3 by binding to their 3'UTRs and contribute to the development of T1D. PMID: 29859273 the expression of mCTLA-4 in skin lesion inversely correlated with the severity of psoriasis and CTLA-4 might play a critical role in the disease severity of psoriasis. PMID: 29305257 Hematopoietic stem cell transplantation for CTLA4 deficiency with pathogenic mutations resulting in complex immune dysregulation syndromes. PMID: 27102614 Our results suggest that CTLA-4 may be involved in lipid metabolism and affect Type 2 diabetes mellitus (T2DM)disease progression and/or the development of diabetic complications although this gene does not represent a major risk factor for T2DM. PMID: 29511375 rs231775, rs4553808 and rs5742909 but not rs3087243 and rs733618 were significantly related to cancer risk. In analyses stratified by ethnicity, both rs231775 and rs4553808 were significant susceptibility polymorphisms in an Asian population but not in a Caucasian population. PMID: 29794444 Paper analyses results of serum cytokines and lymphocyte apoptosis study in nodular goiter against the background of autoimmune thyroiditis and thyroid adenoma based on the cell preparedness to apoptosis, the number of apoptotic lymphocytes and the content of proapoptotic tumor necrosis factor-alpha, interleukins in serum, considering the polymorphism of BCL-2, CTLA-4 and APO-1 genes. PMID: 29250672 -318C/T polymorphism of CTLA-4 gene might play a significant role in the development of SLE in the Iranian patients. PMID: 24400885 the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor PMID: 28827064 It was concluded that the abnormal expression of endometrial E2A existed in mid-secretory endometrium of women with recurrent miscarriage, and there was a positive correlation between E2A and FOXP3, and E2A and CTLA-4, suggesting the possible regulatory role of E2A in endometrium receptivity. PMID: 29270752 This study shows a significant overexpression of CTLA-4 in >50% of breast carcinomas with no such overexpression of CTLA-4 in benign breast tissues. PDL-1 staining is seen in only a small number of invasive ductal carcinomas (4.1%). PMID: 29672601 CTLA4 gene is suggested to correlated with polycyctic ovary syndrome, and influence polycycstic ovary syndrome through regulating obesity and the homeostatic model assessment for insulin resistance in a novel way. PMID: 30024513 We describe three cases of patients with mRCC treated with anti-PD-1 antibody therapy in combination with targeted therapy (bevacizumab), anti-cytotoxic T lymphocyte antigen 4 therapy (ipilimumab), or radiotherapy. PMID: 29146617 The CTLA-4c.49A>G and CTLA-4g.319C>T single nucleotide polymorphisms might be considered as low risk susceptibility locus for prostate cancer PMID: 28101800 anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%; P = 0.004) and PFS (P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. PMID: 28835386 Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases. PMID: 28750137 this study showed that CTLA-4 + 49A/G polymorphism was not correlated with greater genetic risk for leprosy. However, GG genotype was associated with older age, older age of onset and over-representation in male in an Iranian Azeri population. PMID: 29104093 Our meta-analysis suggested that the +49 A/G polymorphism in CTLA4 might be a risk factor for asthma susceptibility, especially in Asian individuals, children, and patients with atopy PMID: 29995780 Genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in patients with Graves' disease. PMID: 29093229 These results demonstrate that POSTN promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and that CTLA4 enhances the ectopic osteogenesis of MSCs-CTLA4-based tissue-engineered bone. PMID: 28687929 the polymorphism -318C/T of CTLA-4 gene is associated with RBC alloimmunization among sickle cell disease patients. This highlights the role played by CTLA-4 on post-transfusion alloantibody development PMID: 28815969 Meta-analysis found that CTLA4 -318C/T gene polymorphism is not associated with the risk of acute rejection in renal transplantation in overall populations. PMID: 28449371 Our goal was to stimulate antitumor immunity by combining SS1P or LMB-100 with anti-CTLA-4. We constructed a BALB/c breast cancer cell line expressing human mesothelin (66C14-M), which was implanted in one or two locations. SS1P or LMB-100 was injected directly into established tumors and anti-CTLA-4 administered i.p. In mice with two tumors, one tumor was injected with immunotoxin and the other was not. PMID: 28674083 Taken together, we found that Id3+ and CTLA-4+ endometrial cells were significantly higher in women with repeated implantation failure and recurrent miscarriage, suggesting the negative roles of these angiogenesis and immune tolerance markers involving in regulating endometrium receptivity. PMID: 28224680 study indicated that the polymorphisms of rs231775 and rs231725 would be the risk factors of Primary Biliary Cholangitis [meta-analysis] PMID: 28642883 Suggest that genetic polymorphisms of CTLA-4 function as sex-dependent risk factors for development of acute rejection in an Iranian kidney transplant population. PMID: 28031007 A phase Ib study of dasatinib plus ipilimumab in patients with gastrointestinal stromal tumor (GIST) and other sarcomas was performed on the basis of preclinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. PMID: 28007774 The data we presented here showed that CTLA-4 was highly expressed in regulatory T cells and PD-1 decreased in CD8+ T cells in peripheral blood of SCLC patients, suggesting their unique mechanisms involved in immune regulation. PMID: 29167005 Significant differences in the CpG-methylation patterns between tumor tissues and matched controls were observed for CTLA4 showing a decreased methylation of this gene in non-small cell lung cancer patients. Expression studies confirmed that hypomethylation also resulted in increased expression of CTLA4. PMID: 28503213 The polymorphisms +49 G/A, -1661 A/G and -318 C/T may elevate the susceptibility to BC, but the polymorphism CT60 G/A may offer protection against the cancer. PMID: 28416762 In children with idiopathic nephrotic syndrome (INS), serum CTLA-4 concentration significantly increased at remission compared with onset. Furthermore, a positive significant correlation was observed between Treg number and serum CTLA-4 level. This suggests that Treg and CTLA-4 are involved in the induction of remission in INS. PMID: 28544686

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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