Recombinant Human Glucocorticoid Receptor (NR3C1) Protein (His-GST)

Name: Recombinant Human Glucocorticoid Receptor (NR3C1) Protein (His-GST)
Brand: Beta LifeScience
SKU: BLC-03443P
Availability: InStock

Greater than 85% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human Glucocorticoid Receptor (NR3C1) Protein (His-GST) is produced by our E.coli expression system. This is a protein fragment.
Purity	Greater than 85% as determined by SDS-PAGE.
Uniprotkb	P04150
Target Symbol	NR3C1
Synonyms	GCCR; GCR; GCR_HUMAN; GCRST; glucocorticoid nuclear receptor variant 1; Glucocorticoid receptor; GR; GRL; Grl1; nr3c1; Nuclear receptor subfamily 3 group C member 1; nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-10His-GST
Target Protein Sequence	VPATLPQLTPTLVSLLEVIEPEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSWMFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK
Expression Range	521-777aa
Protein Length	Partial
Mol. Weight	61.3 kDa
Research Area	Epigenetics And Nuclear Signaling
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth.; Has transcriptional activation and repression activity. Mediates glucocorticoid-induced apoptosis. Promotes accurate chromosome segregation during mitosis. May act as a tumor suppressor. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression.; Acts as a dominant negative inhibitor of isoform Alpha. Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed. Loses this transcription modulator function on its own. Has no hormone-binding activity. May play a role in controlling glucose metabolism by maintaining insulin sensitivity. Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner. Directly regulates STAT1 expression in isoform Alpha-independent manner.; Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism.; Increases activity of isoform Alpha.; More effective than isoform Alpha in transcriptional activation, but not repression activity.; Has transcriptional activation activity.; Has transcriptional activation activity.; Has transcriptional activation activity.; Has highest transcriptional activation activity of all isoforms created by alternative initiation. Has transcriptional repression activity. Mediates glucocorticoid-induced apoptosis.; Has transcriptional activation activity.; Has transcriptional activation activity.; Has lowest transcriptional activation activity of all isoforms created by alternative initiation. Has transcriptional repression activity.
Subcellular Location	[Isoform Alpha]: Cytoplasm. Nucleus. Mitochondrion. Cytoplasm, cytoskeleton, spindle. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.; [Isoform Beta]: Nucleus. Cytoplasm.; [Isoform Alpha-B]: Nucleus. Cytoplasm.
Protein Families	Nuclear hormone receptor family, NR3 subfamily
Database References	HGNC: 7978 OMIM: 138040 KEGG: hsa:2908 STRING: 9606.ENSP00000231509 UniGene: Hs.122926
Associated Diseases	Glucocorticoid resistance, generalized (GCCR)
Tissue Specificity	Widely expressed including bone, stomach, lung, liver, colon, breast, ovary, pancreas and kidney. In the heart, detected in left and right atria, left and right ventricles, aorta, apex, intraventricular septum, and atrioventricular node as well as whole a

Gene Functions References

relaxin-GR signaling has role in hepatocellular protection against ischemia-reperfusion stress in liver transplantation PMID: 29350771
Bcl1 G/G polymorphism of glucocorticoid receptor gene is associated with bronchial asthma complicated by obesity. PMID: 30480407
topical mevastatin accelerates wound closure by promoting epithelialization via multiple mechanisms: modulation of GR ligands and induction of the long noncoding RNA Gas5, leading to c-Myc inhibition. PMID: 29158265
alpha-Viniferin (KCV) inhibits the activation of glucocorticoid receptor (GR) signaling pathway in non-androgen-dependent Prostate cancer (PCa) cells. KCV induces cancer cell apoptosis through AMP-Activated Protein Kinases-mediated activation of autophagy, and inhibits GR expression in castration-resistant prostate cancer(CRPC). PMID: 29904891
The genotypes for the NR3C1 polymorphisms in patients and controls were distributed as follows: rs6191 TT 37 : 56, GT 178 : 36, GG 332 : 609; rs6196 AA 483 : 905, AG 66 : 118, GG 2 : 4; rs10482614 GG 493 : 916, AG 61 : 108, AA 1 : 4; and rs72557310 AG 27 : 65, GG 3 : 0, AA 525 : 964. There were no significant differences in genotype frequency or in allele distributions between cases and controls. PMID: 29381656
Glucocorticoid receptor positively regulates transcription of FNDC5 in the liver. PMID: 28240298
Polymorphisms in NR3C1 gene is associated with sensitivity to glucocorticoids and it may contribute to the glucose abnormality for Acute Lymphoblastic Leukemia. PMID: 29802709
NR3C1 methylation moderates the effect of maternal support during stress on anxious attachment development 18 months later. More stressed children who experienced less maternal support reported increased anxious attachment when their NR3C1 gene was highly methylated. This effect could not be explained by children's level of psychopathology. PMID: 29058930
Meta-analysis showed that homozygous mutation of NR3C1 rs41423247 was associated with Depression. PMID: 30278546
This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. [review] PMID: 29685454
study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of systemic lupus erythematosus PMID: 28984075
The BclI NR3C1 polymorphisms were significantly associated with asthma in adults. (Meta-analysis) PMID: 29729712
Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. PMID: 29738565
There was no significant association between different genotypes and alleles of Glucocorticoid Receptor of rs6195, rs6189/rs6190 variants, and response to fluoxetine (p=0.213 and 0.99, respectively). PMID: 28641498
NR3C1 gene polymorphisms are significantly associated with the response to glucocorticoids. PMID: 29207898
There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians (review and meta-analysis). PMID: 29526633
Analyses demonstrated a trend in the association between maternal trait anxiety and depression symptoms with placental gene expression of NR3C1. We found a significant interaction with maternal ethnicity. In Caucasians only, prenatal trait anxiety and depressive symptoms were associated with an increase in placental NR3C1 expression, and prenatal life events were associated with a down regulation of HSD11B2 PMID: 29100173
We genotyped 10 single nucleotide polymorphisms (SNPs) on the NR3C1 gene (rs10482682, rs33389, rs10482633, rs10515522, rs2963156, rs4128428, rs9324918, rs41423247, rs6189, rs10052957).Haplotype analyses revealed significant effects of NR3C1 (p = 0.011) on cortisol stress response. Neither NR3C1 haplotype nor NR3C2 haplotype was associated with reasoning abilities. PMID: 29100174
In this study, we described the cellular localization of the glucocorticoid receptor in the human adult and fetal testis and provided evidence of an association between semen quality and a genetic polymorphism BclI (rs41423247) in the NR3C1 gene. PMID: 28992366
Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. PMID: 29162170
children with early onset maltreatment evidence significant hypermethylation compared to nonmaltreated children. Also, hypermethylation of NR3C1 is linked with a number of negative child outcomes including greater emotional lability-negativity, higher levels of ego undercontrol, more externalizing behavior, and greater depressive symptoms. PMID: 29162187
Study evaluated whether associations between early adversity and brain responses to dynamic facial expressions in early adulthood varied as a function of regional differences in the expression of NR3C1. Strongest associations between adversities and BOLD response to fearful faces were in brain regions with higher NR3C1 mRNA expression levels. Highest expression of NR3C1 is found in occipital and lowest in temporal regions PMID: 28612935
Study define a distinct GRgamma driven signaling network including identification of GRgamma specific subcellular trafficking, target gene selection, and engagement of interacting proteins. Both transcriptome, and protein interactome data suggested a role in for GRgamma in directing mitochondrial function, and indeed GRgamma expression increased mitochondrial mass, basal respiration, and ATP generation. PMID: 27226058
Studied single nucleotide polymorphisms in human glucocorticoid receptor (NR3C1) gene with regard to susceptibility in high-altitude pulmonary edema (HAPE) in Han Chinese population. PMID: 29587872
In patients with adrenal incidentalomas, a 5% prevalence of heterozygous NR3C1 mutations was discovered. PMID: 29444898
This study demonstrated that NR3C1 expression levels are related to major depressive disorder and conjunctly mediate the effect of childhood maltreatment history on the risk of developing major depressive disorder. PMID: 28384542
This study demonstrated that increased methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of patients with generalized anxiety disorder. PMID: 28292649
This study suggests that SNPs in the NR3C1 gene may influence BDNF levels in crack cocaine addiction. PMID: 28237884
We identified a molecular signature of secreted proteins associated with AA ultraresponsiveness and sustained AR/GR signaling upon AA resistance in intermediate or minimal responders. These data will inform development of noninvasive biomarkers predicting AA response and suggest that further inhibition along the AR/GR signaling axis may be effective only in AA-resistant patients who are intermediate or minimal responders PMID: 27993966
A Tri-Nucleotide Pattern in a 3' UTR Segment Affects The Activity of a Human Glucocorticoid Receptor Isoform PMID: 27660999
Association Between N363S and BclI Polymorphisms of the Glucocorticoid Receptor Gene (NR3C1) and Glucocorticoid Side Effects During Childhood Acute Lymphoblastic Leukemia Treatment. PMID: 28179212
genetic association studies in population in Brazil: Data suggest that an SNP in NR3C1 (A3669G) is associated with appetite regulation and food preferences; here, adolescents carrying A3669G variant exhibited decreased comfort food intake. PMID: 28400302
Results provide evidence for an association between the NR3C1-rs41423247 SNP and depression: C minor allele of rs41423247 increased depressive symptoms during early abstinence of women with crack cocaine addiction, but it did not have effects over detoxification treatment. A slight effect of CC genotype was shown at late abstinence phase. C allele of this SNP was associated to an increased number of rehospitalizations. PMID: 27397864
There was no significant interaction between NR3C1 and stressful life events with respect to alcohol use/misuse. PMID: 26751645
Dehydroepiandrosterone (DHEA) and cortisol modulate SRSF9 and SRSF3 in a different way and data suggest that the anti-glucocorticoid effect of DHEA, among other mechanisms, is also exerted by modulating the expression of proteins involved in the splicing of the GR pre-mRNA. PMID: 28373129
Association between suicide and altered NR3C1 gene expression in the prefrontal cortex. PMID: 27030168
Results identified three novel heterozygous missense NR3C1 mutations causing glucocorticoid resistance in patients with adrenal incidentalomas without Cushing's syndrome. p.R477S and p.Y478C are located in the DNA binding domain (DBD) of the glucocorticoid receptor (GR) while p.L67P is located in the ligand binding domain of GR. PMID: 27120390
Data show that the 3' UTR of glucocorticoid receptor beta (GRbeta) is regulated by miR144. PMID: 27036026
Except for a slightly higher risk of bronchopulmonary dysplasia (BPD) in carriers of the GRBclI variant, the glucocorticoid receptor gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of Very-Low-Birth-Weight preterm infants. PMID: 27509264
Possible influence of BclI C/G polymorphism (rs41423247) on hippocampal shape and integrity of the parahippocampal subdivision of the cingulum in depression. PMID: 27428087
A woman with glucocorticoid resistance and her mother had a novel p.Arg477Cys (c.1429C>T) mutation in exon 4 of NR3C1, in the 2dzinc finger of the DNA-binding domain. Its 'in silico' functional effect was assessed using pathogenicity prediction software, being characterized as pathogenic. An unrelated patient had a novel p.His588Leufs*5 (c.1762_1763insTTAC) mutation, in exon 6, in the ligand binding domain. PMID: 27211791
NR3C1 as an important gene of the hypothalamic-pituitary-adrenal axis seems to be particularly relevant for the pathophysiology of ADHD combined with comorbid CD. PMID: 27741480
a significant protein-protein interaction between GR and CHOP, (GR-CHOP heterocomplex formation) under endoplasmic reticulum stress conditions, is reported. PMID: 27496643
Childhood Maltreatment and MDD are both associated wit haltered DNA methylation levels in the NR3C1 promoter region, however the location and direction of effects differ between the two exposure.s PMID: 27475889
This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. PMID: 27378548
genetic association studies in a racially diverse population in North Carolina: Data suggest that an SNP in NR3C1 (rs6191, G3134T, "glucocorticoid receptor beta") is associated with altered gene expression profile in primary macrophages; minor allele frequency is 74% with a higher prevalence in Caucasian non-Hispanic participants. PMID: 28759007
Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels. PMID: 27653086
G-allele was associated with childhood overweight, depressive disorder comorbidity, and diagnostic instability. G-allele carriers reporting childhood overweight showed greater frequency of subjective binge eating and emotional eating. PMID: 27400218
haplotype TAAT of GR might be a protective factor against aggressive behavior, while gene-gene interactions between GR rs1800445 and MR (NR3C2) rs2070951 might be a risk factor for aggressive behavior in the Central South Chinese Han population PMID: 28686058
Glucocorticoid receptor (GR) is recruited to activator protein-1 (AP-1) target genes in a DNA-binding-dependent manner. PMID: 28591827

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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.

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