KDM4A

Lysine (K)-specific demethylase 4A

PDB rendering based on 2gf7.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2GF7, 2GFA, 2GP3, 2GP5, 2OQ6, 2OQ7, 2OS2, 2OT7, 2OX0, 2P5B, 2PXJ, 2Q8C, 2Q8D, 2Q8E, 2QQR, 2QQS, 2VD7, 2WWJ, 2YBK, 2YBP, 2YBS, 3NJY, 3PDQ, 3RVH, 3U4S, 4AI9, 4BIS, 4GD4, 4V2V, 4V2W

Identifiers

Symbols

KDM4A ; JHDM3A; JMJD2; JMJD2A; TDRD14A

External IDs

OMIM: 609764 MGI: 2446210 HomoloGene: 27780 IUPHAR: 2675 ChEMBL: 5896 GeneCards: KDM4A Gene

EC number

1.14.11.-

Gene ontology
Molecular function	• protein binding • zinc ion binding • ubiquitin protein ligase binding • methylated histone binding • histone demethylase activity (H3-K36 specific)
Cellular component	• nucleus • nucleoplasm • nucleolus • cytoplasm
Biological process	• chromatin organization • transcription, DNA-templated • cardiac muscle hypertrophy in response to stress • viral process • histone demethylation • negative regulation of transcription, DNA-templated • oxidation-reduction process • histone H3-K36 demethylation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
43.65 – 43.71 Mb

Chr 4:
118.14 – 118.18 Mb

PubMed search

Lysine-specific demethylase 4A is an enzyme that in humans is encoded by the KDM4A gene.^[1]^[2]^[3]

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor.^[3]

Alterations in this gene have been found associated with chromosomal instability that leads to cancer.(PMID 23871696)

References

↑ Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Dec 1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res 5 (3): 169–176. doi:10.1093/dnares/5.3.169. PMID 9734811.
↑ Katoh M, Katoh M (May 2004). "Identification and characterization of JMJD2 family genes in silico". Int J Oncol 24 (6): 1623–8. doi:10.3892/ijo.25.3.759. PMID 15138608.
1 2 "Entrez Gene: JMJD2A jumonji domain containing 2A".

Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Yoon HG, Chan DW, Reynolds AB, et al. (2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Mol. Cell 12 (3): 723–734. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–716. doi:10.1038/nbt971. PMID 15146197.
Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Res. 14 (9): 1711–1718. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Gray SG, Iglesias AH, Lizcano F, et al. (2005). "Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein". J. Biol. Chem. 280 (31): 28507–28518. doi:10.1074/jbc.M413687200. PMID 15927959.
Zhang D, Yoon HG, Wong J (2005). "JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2)". Mol. Cell. Biol. 25 (15): 6404–6414. doi:10.1128/MCB.25.15.6404-6414.2005. PMC 1190321. PMID 16024779.
Tao WA, Wollscheid B, O'Brien R, et al. (2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry". Nat. Methods 2 (8): 591–598. doi:10.1038/nmeth776. PMID 16094384.
Kim J, Daniel J, Espejo A, et al. (2006). "Tudor, MBT and chromo domains gauge the degree of lysine methylation". EMBO Rep. 7 (4): 397–403. doi:10.1038/sj.embor.7400625. PMC 1456902. PMID 16415788.
Huang Y, Fang J, Bedford MT, et al. (2006). "Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A". Science 312 (5774): 748–751. doi:10.1126/science.1125162. PMID 16601153.
Whetstine JR, Nottke A, Lan F, et al. (2006). "Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell 125 (3): 467–481. doi:10.1016/j.cell.2006.03.028. PMID 16603238.
Chen Z, Zang J, Whetstine J, et al. (2006). "Structural insights into histone demethylation by JMJD2 family members". Cell 125 (4): 691–702. doi:10.1016/j.cell.2006.04.024. PMID 16677698.
Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature 441 (7091): 315–321. doi:10.1038/nature04727. PMID 16710414.
Klose RJ, Yamane K, Bae Y, et al. (2006). "The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36". Nature 442 (7100): 312–316. doi:10.1038/nature04853. PMID 16732292.
Shin S, Janknecht R (2007). "Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D". Biochem. Biophys. Res. Commun. 359 (3): 742–746. doi:10.1016/j.bbrc.2007.05.179. PMID 17555712.
Chen Z, Zang J, Kappler J, et al. (2007). "Structural basis of the recognition of a methylated histone tail by JMJD2A". Proc. Natl. Acad. Sci. U.S.A. 104 (26): 10818–10823. doi:10.1073/pnas.0704525104. PMC 1891149. PMID 17567753.
Ng SS, Kavanagh KL, McDonough MA, et al. (2007). "Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity". Nature 448 (7149): 87–91. doi:10.1038/nature05971. PMID 17589501.
Lee J, Thompson JR, Botuyan MV, et al. (2008). "Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor". Nat. Struct. Mol. Biol. 15 (q): 109–111. doi:10.1038/nsmb1326. PMC 2211384. PMID 18084306.

PDB gallery

2gf7: Double tudor domain structure

2gfa: double tudor domain complex structure

2gp3: Crystal structure of the catalytic core comain of jmjd2a

2gp5: Crystal structure of catalytic core domain of jmjd2A complexed with alpha-Ketoglutarate

2oq6: Crystal structure of JMJD2A complexed with histone H3 peptide trimethylated at Lys9

2oq7: The crystal structure of JMJD2A complexed with Ni and N-oxalylglycine

2os2: Crystal structure of JMJD2A complexed with histone H3 peptide trimethylated at Lys36

2ot7: Crystal structure of JMJD2A complexed with histone H3 peptide monomethylated at Lys9

2ox0: Crystal structure of JMJD2A complexed with histone H3 peptide dimethylated at Lys9

Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)

1.14.11: 2-oxoglutarate	Prolyl hydroxylase Lysyl hydroxylase

1.14.13: NADH or NADPH	Flavin-containing monooxygenase FMO1 FMO2 FMO3 FMO4 FMO5 Nitric oxide synthase NOS1 NOS2 NOS3 Cholesterol 7 alpha-hydroxylase Methane monooxygenase 3A4 Lanosterol 14 alpha-demethylase 24-hydroxycholesterol 7α-hydroxylase

1.14.14: reduced flavin or flavoprotein	19A1 2D6 2E1

1.14.15: reduced iron-sulfur protein	11B1 11B2 11A1

1.14.16: reduced pteridine (BH4 dependent)	Phenylalanine hydroxylase Tyrosine hydroxylase Tryptophan hydroxylase

1.14.17: reduced ascorbate	Dopamine beta-hydroxylase

1.14.18-19: other	Tyrosinase Stearoyl-CoA desaturase-1

1.14.99 - miscellaneous	Cyclooxygenase Heme oxygenase (HMOX1) Squalene monooxygenase 17A1 21A2

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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KDM4A

References

Further reading