KDM1A: A Flavin Containing Domain 2 Drug Target and Biomarker

Target Name: KDM1A

NCBI ID: G23028

KDM1A: A Flavin Containing Domain 2 Drug Target and Biomarker

KDM1A, also known as amine oxidase (flavin containing) domain 2, is a protein that plays a crucial role in cellular metabolism. It is a key enzyme in the UmeoQ subfamily of NAD+-dependent enzymes, which are involved in the transfer of electrons in the electron transport chain (ETC) of the cell's energy metabolism. Specifically, KDM1A is involved in the oxidation of amines, such as histidine and tyrosine, to their respective amino acids.

KDM1A's unique catalytic mechanism allows it to handle a wide range of substrate amines with different redox states. It does this by utilizing a distinct Chuton-Auer effect (Chughton-Auer effect), which involves a coordinated redox reaction that Churton and Orr first proposed it in 1958. By studying the crystallographic and biochemical properties of KDM1A, the scientists revealed the detailed mechanism of this effect and confirmed that it is a key factor in KDM1A's catalytic activity.

KDM1A plays a variety of biological functions in organisms. In neurobiology, loss of KDM1A can lead to neuronal degeneration and even neurological failure. In addition, in tumorigenesis, the activation of KDM1A can lead to the invasion and metastasis of tumor cells and is therefore considered a potential tumor therapeutic target. In immunology, inhibition of KDM1A can enhance the function of immune cells, thereby having an impact on the treatment of immune diseases.

Currently, KDM1A has become a popular target in the field of drug research and development. Due to the diverse biological functions of KDM1A in organisms, many research teams are exploring its use as a drug target to treat various diseases. Among them, some research teams are exploring the use of KDM1A inhibitors to treat neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. In addition, some research teams are exploring the use of KDM1A inhibitors to treat tumors in order to achieve complete control of tumor cells.

In addition to its application in drug development, KDM1A is also used as a biomarker. Due to KDM1A's critical role in cellular metabolic processes, it plays an important role in many biological processes. For example, KDM1A regulates S-phase DNA synthesis during the cell cycle and is a key factor in cell cycle progression and mitosis. In addition, KDM1A is also involved in the regulation of apoptosis and is a key player in the apoptosis signaling pathway. Therefore, by detecting the activity or expression level of KDM1A, quantitative analysis of cellular metabolic status and biological processes can be performed, providing valuable information for biological research.

In short, KDM1A, as an important enzyme, has multiple biological functions in organisms. At the same time, KDM1A has broad application prospects in drug development and biomarker research. With the continuous development of science and technology, more research teams are expected to explore the potential of KDM1A in the fields of biology and medicine in the future and realize its widespread application in clinical treatment.

Protein Name: Lysine Demethylase 1A

Functions: Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16140033, PubMed:16079794, PubMed:16079795, PubMed:16223729). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16140033, PubMed:16079794, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281)

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