KDM2A

Official Full Name

lysine demethylase 2A

Organism

Homo sapiens

Gene ID

22992

Background

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

Synonyms

FBL7; CXXC8; FBL11; FBXL11; JHDM1A; LILINA

Cat.No.	Product Name	Price
CSC-DC008041	Panoply™ Human KDM2A Knockdown Stable Cell Line	Inquiry
CSC-SC008041	Panoply™ Human KDM2A Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD08499Z	Human KDM2A adenoviral particles	Inquiry
LV16104L	human KDM2A (NM_012308) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH050763	shRNA set against Mouse Fbxl11(NM_001001984.2)	Inquiry
SHH324147	shRNA set against Human KDM2A (NM_012308.2)	Inquiry
SHH324151	shRNA set against Mouse KDM2A (NM_001001984.2)	Inquiry
SHH324155	shRNA set against Rat KDM2A (NM_001108515.1)	Inquiry

Cat.No.	Product Name	Price
CDCL123583	Human KDM2A ORF clone (NM_001256405.1)	Inquiry
CDFR008127	Rat Kdm2a cDNA Clone(NM_001108515.1)	Inquiry
MiUTR1M-04600	KDM2A miRNA 3'UTR clone	Inquiry
MiUTR4H-TG04753	KDM2A miRNA 3'UTR clone	Inquiry
CDCB186102	Rabbit KDM2A ORF clone (XM_008273687.1)	Inquiry
CDCL123587	Mouse Kdm2a ORF clone (NM_001001984.2)	Inquiry
CDCR375008	Rat Kdm2a ORF Clone(NM_001108515.1)	Inquiry

Detailed Information

Recent Research

KDM2A has two isoforms: the long isoform consists of the JmjC domain, CXXC-zinc finger, PHD zinc finger, F-box and AMN1 protein (Core relocalization and spindle detection of proteins); and the short isoform lacks the N-terminal JmjC domain but contains all other motifs. KDM2A is a histone demethylase that selectively removes monomethylation and dimethylation from histone H3K36. It has been reported that KDM2A has histone demethylase activity in vivo on dimethylated Lys 36 of histone H3 (H3K36me2), and H3K36me2 (h3k36me1/2) is added to monomethylated Lys 36 of histone H3 (H3K36me1) in vitro. The amino acid sequences of human KDM2A were 97.4 and 87.0% of Mus musculus and Gallus Gallus, respectively. These suggest that KDM2A plays an important role in higher animals.KDM2A had the highest correlation between copy number and mRNA expression, and high mRNA levels of KDM2A were significantly associated with lower survival rates in breast cancer patients. Study on human prostate cancers showed low levels of KDM2A in prostate cancers while a recent study states that high levels of KDM2A correlates with poor prognosis in NSCLC (nonsmall-cell lung cancer) patients.

KDM2A was identified as a novel substrate of ATM. DSB (Double Strand Break) enhanced the interaction between ATM and KDM2A, which induced ATM-mediated phosphorylation of KDM2A at T632. The specific KDM2A T632 phosphorylation compromised its chromatin-binding capacity and thus alleviated its ability to demethylate H3K36me2. Consequently, H3K36 dimethylation level, especially at DNA damage sites, significantly increased. High levels of H3K36me2 recruited the MRE11 (composed of the meiotic recombination 11) complex to the DNA damage sites via a direct interaction with NBS1 and thus contributed to the ability of cells to repair DSBs.

KDM2A inhibits HDAC3 (histone deacetylase 3) gene expression by demethylating H3K36me2 at the HDAC3 promoter. KDM2A enhanced the expression of CDK6 and NEK7, cell cycle related genes, and NANOS1 and RAPH1, cell invasion-related genes in NSCLC cells. Interestingly, the expression of these genes was directly inhibited by the transcription corepressor HDAC3. Therefore, current studies have revealed that KDM2A-mediated inhibition of HDAC3 expression may antagonize the molecular mechanism of transcriptional inhibition of cell cycle-associated genes and invasively related genes by HDAC3 in KAC2A overexpressing lung cancer cells (ie, KDM2A HDAC3 cell cycle/invasive gene) (eg CDK6 and NANOS1)). Furthermore, KDM2A-mediated regulation of HDAC3 expression may depend to a large extent on the catalytic activity of KDM2A, as KDM2A catalyzed mutants do not inhibit HDAC3 expression.

KDM2A needs to maintain centromere integrity and genomic stability, especially during mitosis. Inhibition of E2F1 maintains normal cellular function and integrity. And KDM2A acts as a co-regulator of E2F1-mediated gene transcription, angiogenesis and metastasis. KDM2A is primarily expressed in MEPC (microencapsulated phase change slurry) of human breast structure. KDM2A is associated with cell cycle-dependent Rb (retinoblastoma tumor suppressor protein) and E2F1 (Cell cycle related transcription factors 1) in breast cancer cells. Any changes in the myoepithelial cell line and myoepithelial cell layer of the myoepithelial system reflect the pathological changes in the breast. Primary breast cancer typically exhibits a significant increase in lumen to myoepithelial cells, and many invasive breast cancers are completely devoid of MEPC. KDM2A is present at low levels in ductal cells. Normal ducts and intact ducts in ductal carcinoma tissue sections showed that myoepithelial cells were strongly positive for KDM2A, indicating that KDM2A has regulatory functions in these cells. As the disease progresses to malignancy, myoepithelial cell dispersion is found in breast cancer tissue sections.

References:

Dhar S S, et al. Transcriptional Repression of Histone Deacetylase 3 by the Histone Demethylase KDM2A Is Coupled to Tumorigenicity of Lung Cancer Cell. Journal of Biological Chemistry, 2014, 289(11):7483-7496.
Tanaka Y, et al. Mild glucose starvation induces KDM2A-mediated H3K36me2 demethylation through AMPK to reduce rRNA transcription and cell proliferation. Molecular & Cellular Biology, 2015, 35(24):4170-84.
Liu H, et al. Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer. Molecular Carcinogenesis, 2015, 55(5):977-990.
Kawakami E, et al. The histone demethylase Fbxl11/Kdm2a plays an essential role in embryonic development by repressing cell-cycle regulators. Mechanisms of Development, 2015, 135:31-42.

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