D
IPR047482

Lysine-specific demethylase 4A, extended PHD finger

InterPro entry
Short nameJMJD2A_ePHD
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents the extended PHD (ePHD) finger of KDM4A.

Lysine-specific demethylase 4A (KDM4A), also known as JMJD2A or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyses the demethylation of di- and trimethylated histone H3, specifically at 'Lys-9' and 'Lys-36' positions (H3K9 and H3K36)
[12, 1, 5, 3, 7, 2]
. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor corepressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER), and plays an essential role in growth of both ER-positive and -negative breast tumours
[11, 6, 8, 10, 4]
. It is also involved in prostate, colon, and lung cancer progression
[9, 13]
. JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains
[12]
.

References

1.Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A. Huang Y, Fang J, Bedford MT, Zhang Y, Xu RM. Science 312, 748-51, (2006). View articlePMID: 16601153

2.A comparative molecular dynamics study of methylation state specificity of JMJD2A. Ulucan O, Keskin O, Erman B, Gursoy A. PLoS One 6, e24664, (2011). PMID: 21931800

3.The histone trimethyllysine demethylase JMJD2A promotes cardiac hypertrophy in response to hypertrophic stimuli in mice. Zhang QJ, Chen HZ, Wang L, Liu DP, Hill JA, Liu ZP. J Clin Invest 121, 2447-56, (2011). PMID: 21555854

4.Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G(1)/S transition. Kogure M, Takawa M, Cho HS, Toyokawa G, Hayashi K, Tsunoda T, Kobayashi T, Daigo Y, Sugiyama M, Atomi Y, Nakamura Y, Hamamoto R. Cancer Lett 336, 76-84, (2013). PMID: 23603248

5.Histone demethylase JMJD2A regulates Kaposi's sarcoma-associated herpesvirus replication and is targeted by a viral transcriptional factor. Chang PC, Fitzgerald LD, Hsia DA, Izumiya Y, Wu CY, Hsieh WP, Lin SF, Campbell M, Lam KS, Luciw PA, Tepper CG, Kung HJ. J Virol 85, 3283-93, (2011). PMID: 21228229

6.Oncogenic features of the JMJD2A histone demethylase in breast cancer. Berry WL, Shin S, Lightfoot SA, Janknecht R. Int J Oncol 41, 1701-6, (2012). PMID: 22948256

7.The SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein. Van Rechem C, Black JC, Abbas T, Allen A, Rinehart CA, Yuan GC, Dutta A, Whetstine JR. J Biol Chem 286, 30462-30470, (2011). PMID: 21757720

8.JMJD2A promotes cellular transformation by blocking cellular senescence through transcriptional repression of the tumor suppressor CHD5. Mallette FA, Richard S. Cell Rep 2, 1233-43, (2012). PMID: 23168260

9.The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer cells. Kim TD, Shin S, Berry WL, Oh S, Janknecht R. J Cell Biochem 113, 1368-76, (2012). PMID: 22134899

10.Effects of siRNA-mediated knockdown of jumonji domain containing 2A on proliferation, migration and invasion of the human breast cancer cell line MCF-7. Li BX, Luo CL, Li H, Yang P, Zhang MC, Xu HM, Xu HF, Shen YW, Xue AM, Zhao ZQ. Exp Ther Med 4, 755-761, (2012). PMID: 23170139

11.Effects of RNA interference-mediated gene silencing of JMJD2A on human breast cancer cell line MDA-MB-231 in vitro. Li BX, Zhang MC, Luo CL, Yang P, Li H, Xu HM, Xu HF, Shen YW, Xue AM, Zhao ZQ. J Exp Clin Cancer Res 30, 90, (2011). PMID: 21962223

12.Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer. Liu JS, Fang WK, Yang SM, Wu MC, Chen TJ, Chen CM, Lin TY, Liu KL, Wu CM, Chen YC, Chuu CP, Wang LY, Hsieh HP, Kung HJ, Wang WC. J Biomed Sci 29, 29, (2022). PMID: 35534851

13.C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays. Le Bihan YV, Lanigan RM, Atrash B, McLaughlin MG, Velupillai S, Malcolm AG, England KS, Ruda GF, Mok NY, Tumber A, Tomlin K, Saville H, Shehu E, McAndrew C, Carmichael L, Bennett JM, Jeganathan F, Eve P, Donovan A, Hayes A, Wood F, Raynaud FI, Fedorov O, Brennan PE, Burke R, van Montfort RLM, Rossanese OW, Blagg J, Bavetsias V. Eur J Med Chem 177, 316-337, (2019). PMID: 31158747

Cross References

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