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KDM3A


Official Full Name
lysine demethylase 3A
Organism
Homo sapiens
Gene ID
55818
Background
Enables histone H3K9me/H3K9me2 demethylase activity; iron ion binding activity; and nuclear androgen receptor binding activity. Involved in androgen receptor signaling pathway; formaldehyde biosynthetic process; and positive regulation of DNA-templated transcription. Located in nucleoplasm. Implicated in cervical cancer and colon cancer. Biomarker of Ewing sarcoma; hepatocellular carcinoma; nasopharynx carcinoma; and prostate cancer. [provided by Alliance of Genome Resources, Feb 2025]
Synonyms
TSGA; JMJD1; JHDM2A; JHMD2A; JMJD1A

Cat.No. Product Name Price
SHW001048 shRNA set against Chicken KDM3A (NM_001012891) Inquiry
SHH324171 shRNA set against Human KDM3A (NM_018433.5) Inquiry
SHH324175 shRNA set against Mouse KDM3A (NM_001038695.2) Inquiry
SHH324179 shRNA set against Rat KDM3A (NM_175764.2) Inquiry
Cat.No. Product Name Price
CDFH009729 Human KDM3A cDNA Clone(NM_001146688.1) Inquiry
CDFR014872 Rat Kdm3a cDNA Clone(NM_175764.2) Inquiry
MiUTR1R-02735 KDM3A miRNA 3'UTR clone Inquiry
MiUTR3H-11944 KDM3A miRNA 3'UTR clone Inquiry
MiUTR3H-11945 KDM3A miRNA 3'UTR clone Inquiry
CDCB162523 Chicken KDM3A ORF Clone (NM_001012891) Inquiry
CDCB182907 Rabbit KDM3A ORF clone (XM_008254152.1) Inquiry
CDCR233032 Mouse Kdm3a ORF Clone(NM_001038695.2) Inquiry
CDCR271974 Mouse Kdm3a ORF Clone(NM_173001.2) Inquiry
CDCR353489 Human KDM3A ORF Clone(NM_001146688.1) Inquiry
CDCR381919 Rat Kdm3a ORF Clone(NM_175764.2) Inquiry
CDCS418816 Human KDM3A ORF Clone (BC038297) Inquiry

Detailed Information

Recent Research

Lysine demethylase KDM3A (also known as JHDM2A or JMJD1A) is required for male fertility, sex determination and metabolic homeostasis through its nuclear role in chromatin remodeling. Many histone modifying enzymes have additional non-histone substrates and non-enzymatic functions that contribute to all of their biological effects. Therefore, KDM3A is a multifunctional Hsp90 client protein that is directly involved in the regulation of cytoskeletal components.

KDM3A was overexpressed in ewing's sarcoma, and its deletion inhibited the clonal and unanchored growth of multiple patient-derived cell lines, and inhibited tumorigenesis in xenograft models. The absence of KDM3A further increased the level of inhibitive H3K9me2 histone markers in Ewing sarcoma and down-regulated oncogenic factors.

KDM3A played a dual role in breast cancer cell invasion and apoptosis by demethylating histone and the non-histone protein p53, respectively. Through the removal of inhibiting histone H3 lysine methylation of 9 induced genes promotes the attack at the same time, p53 KDM3A through demethylation promote chemical resistance. KDM3A inhibits the pro-apoptotic function of p53 by removing p53-k372me1. Consumption of KDM3A can reactivate mutated p53 to induce the expression of apoptosis-promoting genes in breast cancer with mutant p53. In addition, down-regulation of KDM3A can also effectively inhibit the tumorigenic potential of breast cancer stem-like cells, making them sensitive to apoptosis induced by chemotherapy herapeutic drugs.

Histone lysine demethylase KDM3A plays an important role in homeostasis. Lack of KDM3A promotes cilia development, but these cilia are rich in axonal length, delayed breakdown, and accumulation of intra-flagellate (IFT) protein. KDM3A plays a dual role by regulating actin gene expression and binding to the actin cytoskeleton, producing a responsive "actin gate" involving ARP2/3 activity and IFT. The formation of actin filaments was promoted to rescue ciliary defects caused by KDM3A mutation. In contrast, simultaneous depolymerization of the actin network and IFT overexpression mimic the abnormal cilia trait of the KDM3A mutant. Thus, KDM3A is a negative regulator of cilia production required to regulate IFT protein control by modulating actin dynamics.

KDM3A is involved in TLR4 (Toll-like receptor 4) regulation of Foxp3 (forkhead box P3) transcription. During nuclear transfer of Foxp3, KDM3A binds directly to the Foxp3 promoter and activates its transcription. This will lead to increased foxp3-downstream inhibition of cytokines secretion, including transformation growth factor- 1 (TGF- 1), interleukin 35 (il-35) and heme oxygenase 1 (ho-1), which act as immunosuppressive agents and ultimately promote the immune escape of lung cancer cells. TLR4 activation promotes the expression of H3K9me1/2 demethylase KDM3A. KDM3A directly binds to the Foxp3 promoter and promotes Foxp3 transcription, thereby inducing the secretion of Foxp3-related downstream inhibitory cytokines (TGF-β1, IL-35 and HO-1), and ultimately promoting the immune system escape of lung adenocarcinoma.

References:

  1. Parrish J K, et al. The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing Sarcoma. Oncogene, 2015, 34(2):257-62.
  2. Kasioulis I, et al. KDM3A lysine demethylase is an Hsp90 client required for cytoskeletal rearrangements during spermatogenesis. Molecular Biology of the Cell, 2014, 25(8):1216.
  3. Ramadoss S ,et al. Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53. Oncogene, 2016.
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