Recombinant Human Lysine-Specific Demethylase 6A (KDM6A) Protein (His&Myc)

Name: Recombinant Human Lysine-Specific Demethylase 6A (KDM6A) Protein (His&Myc)
Brand: Beta LifeScience
SKU: BLC-07391P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

Collections: All products, High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Description	Recombinant Human Lysine-Specific Demethylase 6A (KDM6A) Protein (His&Myc) is produced by our E.coli expression system. This is a protein fragment.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	O15550
Target Symbol	KDM6A
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-10His&C-Myc
Target Protein Sequence	KWKLQLHELTKLPAFVRVVSAGNLLSHVGHTILGMNTVQLYMKVPGSRTPGHQENNNFCSVNINIGPGDCEWFVVPEGYWGVLNDFCEKNNLNFLMGSWWPNLEDLYEANVPVYRFIQRPGDLVWINAGTVHWVQAIGWCNNIAWNVGPLTACQYKLAVERYEW
Expression Range	1095-1258aa
Protein Length	Partial
Mol. Weight	26.2 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.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
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	Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A. Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression.
Subcellular Location	Nucleus.
Protein Families	UTX family
Database References	HGNC: 12637 OMIM: 300128 KEGG: hsa:7403 STRING: 9606.ENSP00000367203 UniGene: PMID: 30166694 Lymphomas with low UTX expression express high levels of Efnb1, and cause significantly poor survival. PMID: 30006524 data suggest that haploinsufficiency for KDM6A due to mosaic X chromosome monosomy may be responsible for hyperinsulinism in Turner syndrome. PMID: 29902804 High UTX expression is independently associated with a better prognosis in patients with esophageal squamous cell carcinoma (ESCC) and downregulation of UTX increases ESCC cell growth and decreases E-cadherin expression. Our results suggest that UTX may be a novel therapeutic target for patients with ESCC. PMID: 29351209 Depletion of KDM6A inhibits the expression of SOX9, Col2a1, ACAN and results in increased H3K27me3 and decreased H3K4me3 levels. PMID: 29171124 Rebalance of Histone h3 lysine 27 methylation 3 levels at specific genes through EZH2 inhibitors may be a therapeutic strategy in multiple myeloma cases harboring UTX mutations. PMID: 29045832 both UTX and UTY function as dose-dependent suppressors of urothelial bladder cancer development PMID: 27533081 Two novel missense mutations: p.G325A in the KDM6A gene responsible for Kabuki syndrome and p.G1877V in the SCN1A gene responsible for generalized epilepsy with febrile seizures plus were identified using the TruSight One sequencing panel. PMID: 28442529 inactivating mutations of KDM6A, which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2. PMID: 28228601 Study presents a mutation screening of patients with Kabuki syndrome type 1 which identified 208 mutations in KMT2D. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. PMID: 27302555 Data show that more mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males. PMID: 29136510 Here, we discuss the roles of lysine 27 demethylases, JMJD3 and UTX, in cancer and potential therapeutic avenues targeting these enzymes. Despite a high degree of sequence similarity in the catalytic domain between JMJD3 and UTX, numerous studies revealed surprisingly contrasting roles in cellular reprogramming and cancer, particularly leukemia PMID: 27151432 we identified a novel de novo deletion of KDM6A in a Chinese girl with KS. We consider her allergic skin manifestations to be part of the phenotypic spectrum of KS PMID: 27028180 KDM6A and p21CIP1 expression are essential to curb E7 induced replication stress to levels that do not markedly interfere with cell viability PMID: 28968467 Study identified a feed-forward loop between UTX and ER in the regulation of hormonally responsive breast carcinogenesis. PMID: 28534508 Mutation in KDM6A gene is associated with cancer more frequently in males. PMID: 27869828 Pathogenic variants in KMT2D resulting in protein truncation in 43% (6/14; of which 3 are novel) of all cases were detected, while analysis of KDM6A was negative. MLPA analysis was negative in all instances. PMID: 26841933 Kdm6a and Kdm6b were found to be significantly overexpressed in Malignant pleural mesothelioma (MPM) at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor was potentially useful for treating MPM, revealed that members of the Kdm6 family may not be suitable candidates for therapy PMID: 28197626 The results define UTX as a bivalency-resolving histone modifier necessary for stem cell differentiation PMID: 26762983 UTX gene expression in renal cell carcinoma and bladder cancer. PMID: 27983522 Mutations of the epigenetic genes KMT2D and KDM6A cause dysregulation of certain developmental genes and account for the multiple congenital anomalies of the syndrome PMID: 26898171 UTX positively regulates E-cadherin expression in colon cancer cells. PMID: 26819089 UTX is a prominent tumour suppressor that functions as a negative regulator of EMT-induced Cancer Stem Cell-like properties by epigenetically repressing epithelial-mesenchymal transition -TFs. PMID: 26303947 Kabuki syndrome may be caused by mutations in one of two histone methyltransferase genes: KMT2D and KDM6A. PMID: 26049589 Our results provide further support for the similar roles of KMT2D and KDM6A in the etiology of KS by using a vertebrate model organism to provide direct evidence of their roles in the development of organs and tissues affected in KS patients. PMID: 25972376 Turner Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX expression in immune cells and decreased circulating CD4(+) CXCR5(+) T cell frequency. PMID: 26431949 A report of novel KDM6A mutations in patients with Kabuki syndrome. PMID: 24527667 The KDM6A gene is a histone demethylase specific for histone H3 Lysin 27 and regulates gene transcription [35]. In approximately 24% of urothelial carcinoma, KDM6A is altered. PMID: 26138514 This study is the first to identify frequent BAP1 and BRCA pathway alterations in bladder cancer, show TERT promoter alterations are independent of other bladder cancer gene alterations, and show KDM6A loss is a driver of the bladder cancer phenotype. PMID: 25225064 One girl had a novel splice-site mutation in KDM6A. PMID: 24739679 Mutations in KMT2D gene were identified in 10/16 (62%) of the patients, whereas none of the patients had KDM6A mutations. PMID: 25281733 H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia PMID: 25320243 results demonstrate that UTX is implicated in IL-4 mediated transcriptional activation of the ALOX15 gene PMID: 24465480 Results show that UTX interacts with the retinoic acid receptor alpha (RARalpha) and this interaction is essential for proper differentiation of leukemic U937 cells in response to retinoic acid. PMID: 25071154 Both Ezh2 and Kdm6a were shown to affect expression of master regulatory genes involved in adipogenesis and osteogenesis. PMID: 24123378 High levels of UTX or MLL4 are associated with poor prognosis in patients with breast cancer. PMID: 24491801 The identification of novel KDM6A mutations in patients with Kabuki syndrome. PMID: 23913813 PBRM1, KDM6A, SETD2 and BAP1 were unmethylated in all tumor and normal specimens. PMID: 23644518 KDM6A is overexpressed in breast cancer patients with an unfavorable prognosis (mortality at 1 year, p=8.65E-7). PMID: 23266085 This study demonistrated that KDM6A mutations were most commonly identified in subgroups in medulloblastoma. PMID: 23184418 UTX histone demethylase plays important functional role in epigenetic alteration of HOX clusters during retinoic acid-induced neural differentiation. PMID: 23527641 KDM6A contributes to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation. PMID: 22907667 UTX regulates stem cell migration and hematopoiesis. PMID: 23365460 Microdeletions and microduplications have not been identified in the MLL2 and KDM6A genes of a large cohort of patients with Kabuki syndrome. PMID: 22840376 UXT is a potential interactor of HBV Pol. PMID: 21515470 PAN RNA interacts with demethylases JMJD3 and UTX, and the histone methyltransferase MLL2 PMID: 22589717 identification of Utx as a novel mediator with distinct functions during the re-establishment of pluripotency and germ cell development PMID: 22801502 demonstrate that UTX directly associates with the promoters of the Mll1, Runx1, and Scl genes and modulate their transcription by controlling H3K27me3 marks on respective promoter regions. PMID: 22306297 This study identifies KDM6A mutations as another cause of Kabuki syndrome and highlights the growing role of histone methylases and histone demethylases in multiple-congenital-anomaly and intellectual-disability syndromes. PMID: 22197486 H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERalpha ligand dependency PMID: 21841772

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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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