HSD11B2 Antibodies

Corticosteroid 11-beta-dehydrogenase isozyme 2 (HSD11B2)

Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids.

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Gene Information

Human
Gene Name:	HSD11B2
Uniprot:	P80365
Entrez:	3291

Family

Belongs to:
short-chain dehydrogenases/reductases (SDR) family

Alternative Names

11 betaHSD2; 11 beta-HSD2; AME; corticosteroid 11-beta-dehydrogenase isozyme 2,11-beta-HSD2; EC 1.1.1; EC 1.1.1.-; HSD11B2; HSD11KAME1; HSD2,11-DH2; hydroxysteroid (11-beta) dehydrogenase 2; NAD-dependent 11-beta-hydroxysteroid dehydrogenase; SDR9C3; short chain dehydrogenase/reductase family 9C member 3,11-beta-hydroxysteroid dehydrogenase type 2

Molecular Weight

Mass (kDA):
44.127 kDA

Genomic Context

Human
Location:	16q22.1
Sequence:	16; NC_000016.10 (67431121..67437553)

Tissue Specificity

Expressed in kidney, pancreas, prostate, ovary, small intestine and colon. At midgestation, expressed at high levels in placenta and in fetal kidney and, at much lower levels, in fetal lung and testis (PubMed:8530071).

Subcellular Localizations

Microsome. Endoplasmic reticulum.

Diseases

• Hypertensive Disease
• Cortisol 11-beta-ketoreductase Deficiency
• Mineralocorticoid Excess Syndrome, Apparent
• Essential Hypertension
• Obesity
• Hypernatremia
• Cushing Syndrome
• Kidney Diseases
• Fetal Growth Retardation
• Hypokinesia
• Alkalosis
• Kidney Failure, Chronic
• Diabetes Mellitus

• Neoplasms
• Insulin Resistance
• Acth Syndrome, Ectopic
• Malignant Neoplasms
• Adenoma
• Hyperaldosteronism
• Hereditary Diseases

Pathways

• Excretion
• Secretion
• Localization
• Methylation
• Pathogenesis
• Transport
• Cell Proliferation
• Gluconeogenesis
• Dna Methylation
• Cortisol Secretion
• Cell Growth
• Luteinization
• Aging

• Water Transport
• Luteolysis
• Ovulation
• Hatching
• Response To Water Deprivation
• Osteoblast Differentiation
• Fertilization

PTMs

• Methylation
• Cleavage
• Oxidation

• Demethylation
• Phosphorylation
• Deacetylation

• Acetylation

Research Areas

• Stem Cell Markers

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/HSD11B2

Boster Bio - The Best Uses Of The HSD11B2 Marker

HSD11B2 proteins are essential for enzyme activity, protein stability, and other functions. This gene can be found in the placenta. This antibody is a boster biocertified product. Boster also provides free product credits to first reviewers, who can then use the antibody to discover more about the placental protein. These are some of our favorite uses of this protein in animal studies.

HSD11B2 essential for enzyme activity

The essential role of tyr338 in the catalytic mechanism of HSD11B2 has been emphasized by site-directed mutagenesis studies. These studies show that stability of the protein is dependent on a group of residues ranging from residues 335 through 339. Subcellular distribution studies confirmed that the mutant protein Y338H displayed abnormal localization. The mutation affects hydrophobic stacking as well as substrate binding. A hydrophilic side chain replaces the hydrophobic one. This is not optimal for binding hydrophobic substrates.

The gene encoding HSD11B2 contains 5 exons and is located 6.2 kb in length. It is located close to the ATP6V0D1 Gene. Nawrocki et al. The HSD11B2 promoter is missing a TATA-like part, according to Nawrocki and colleagues (2002). HSD11B2's promoter contains SP1 and SP3, which bind to oligonucleotides.

The HSD11B2 gene is expressed in urine exosomes from AME and EH patients, according to a molecular characterization. The mRNA level of HSD11B2 in urine exosomes varies according to genotype. HSD11B2 also has mRNA that is expected to be present urinary exosomes. HSD11B2 mRNA could be detected in exosomes which could aid in the study mineralocorticoid pathophysiology and hypertension.

Despite its highly conserved structural domains, the HSD11B2 protein also contains several disabling mutations that disrupt its inactive state. One of these mutations, D223N, impairs the stability of the enzyme by converting a positively charged residue into a polar one. It is essential for enzyme stability. These interactions can cause enzyme activity to be reduced.

These studies have shown that the exosomal expression of HSD11B2 genes correlates with both THF+aTHF/THE rates and F/E rates. In the EH population, HSD11B2 levels were positively related to both urinary ratios. However, it is impossible to draw definitive conclusions due to the small study sample. This study will need to be repeated with eplerenone as well as THF+aTHF/THE levels.

The mutations in the HSD11B2 gene have been associated with a range of diseases. These disorders can be life-threatening in young children or mild forms of hypertension in adults. For example, a mutation in this gene results in reduced HSD11B2 activity in humans. Treatment of the affected person is essential for the health of both the mother and the child.

Glu115 is critical for cofactor binding within the HSD11B2 protein. Despite the absence negative charge in glucose115, the deletion mutant didn't result in reduced activity. Researchers stressed the need to perform structure-function analyses in order to identify the role of HSD11B2's glu115. Glu115 was found to be essential for enzyme activities, despite not having a CpG-dinucleotide.

It is crucial for protein stability

The gene for HSD11B2 has 5 exons. It is located at a distance 0.5 kb away from the ATP6V0D1 genes. Nawrocki et al. Nawrocki et al. (2002) discovered that HSD11B2's promoter lacks a TATA-like component. They also found that SP1 and SP3 bound to oligonigonucleotides. HSD11B2 was required for protein stability, according to the authors.

Mutations affecting the tyr338 residue of HSD11B2 severely impair protein stability. The mutation causes a disruption to the salt bridge with D223, as well as a disruption to the hydrogen bond with Y339 which is crucial for protein stability. Mutations in the region cause severe AME, which results in very little or no enzyme activity in vivo.

Although 11bHSD2 activity is rare, it is likely to be a common cause of hypertension in the general population. Studies have shown that patients with essential hypertension are susceptible to heterozygous mutations in the HSD11B2 genes. These mutations can occur even if they do not display typical AME characteristics. Patients with essential hypertension who had homozygous HSD11B2 mutations experienced mild impairments in protein activity. In addition, some relatives of AME suffer from mild hypertension.

HSD11B2 polymorphism is responsible for decreased HSD11B2 activities in asthmatic women who do no take inhaled glucocorticoids. The inflammatory effects of asthma may also interfere with fetal growth. This may make it beneficial to reduce HSD11B2 activities in these patients. There are currently no treatments for phenylketol receptor mediated asthma. However, HSD11B2 gene is likely to be essential for controlling BP.

The structural and functional analysis revealed that HSD11B2 proteins had a disrupted cofactor-binding domain. The protein's activity was not affected by the deletion or addition of glu115. This study highlights the importance and value of a structure-function analysis in this area. This protein may be responsible for 11bHSD2's cofactor-binding speciality.

The exosomal mRNA of HSD11B2 is homozygous for the GG allele in two probands with AME. They had lower levels of HSD11B2 exosomal transcripts, but their eplerenone and blood pressure control and kalemia normalization were better. They discovered that HSD11B2 plays a crucial role in the regulation lipid and protein stability.

Exosomes are a type secreted nucleus. Exosomes are composed of membrane receptors and nucleic acid. HSD11B2 could be found in urine. This may give information about the gene's transcription in urogenital cells. The presence of HSD11B2 mRNA in urine is expected to be beneficial in further studies of pathophysiology and mineralocorticoid hypertension.

Transfection experiments using the HSD11B2 minigenes showed increased expression of 11bHSD2 in the cells. However, the presence short CA repeats is associated a reduced 11bHSD2 activitiy. Additionally, association studies in humans have suggested that there may be a link between this short ALLELE and salt sensitivity. It would be helpful to confirm these findings with a larger data base.

It is expressed in placenta

HSD11B2 can regulate maternal glucorticoid synthesis. Placental placental villi contain two types epithelial cellular types: syncytiotrophoblast & cytotrophoblast. Cytotrophoblasts control the conversion of cortisol to inactive and inactive cortisone. HSD11B2 confers specificity on the mineralocorticoid-receptor.

SybrGreen Real TimePCR was used for determining the mRNA levels in HSD11B2. Perkin Elmer Applied Biosystems' Primer Express software was used to design primers. The primers were created by comparing the published sequences of 11b–HSD2 and GAPDH. These primers contained 690 nM of each gene's promoter region and were proportionally methylated.

We have previously identified a link between epigenetic placental HSD11B2 deregulation and adverse effects on fetal outcome from maternal stress. Both the mother, and the fetus, can benefit from an increased expression of placental HSD11B2. Both mother and fetus can benefit from dietary and epigenetic changes and medications.

Moreover, our study has shown that 11b-HSD2 activity correlates with the cortisone/cortisol ratio in spontaneous birth and C-section placentas. HDS11B2 turnover rates are also related to cortisone/cortisol levels. The correlation between cortisone levels in placental tissue and cortisol levels is therefore very significant.

In a recent study, we observed that DNA methylation levels of the HSD11B2 gene promoter in IUGR neonates were higher. These data suggest a possible link between DNA methylation and gene expression. These findings are of particular interest in the context of the etiopathogenesis of IUGR. These findings could lead to new treatments that reduce the risk of this complication.

To assess HSD11B2 expression, samples of the placenta were collected immediately after delivery. Each subject received eight samples of the placenta parenchyma. These samples were collected 2 cm from the umbilical cord insertion site. The samples were washed with phosphate-buffered soap and stored in liquid nitrogen at the temperature of -80°C until analysis.