KDM4C

KDM4C
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2XDP, 2XML, 4XDO, 4XDP, 5FJK, 5FJH
Identifiers
Aliases	KDM4C, GASC1, JHDM3C, JMJD2C, TDRD14C, bA146B14.1, lysine demethylase 4C
External IDs	OMIM: 605469 MGI: 1924054 HomoloGene: 41004 GeneCards: KDM4C
Gene location (Human)
Chr.	Chromosome 9 (human)
End	7,175,648 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	74,405,860 bp
RNA expression pattern
	Top expressed in
	cerebellar hemisphere; ; stomach; ; corpus callosum; ; colon; ; lung; ; cerebellum; ; sural nerve;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	oxidoreductase activity; histone H3-methyl-lysine-9 demethylase activity; dioxygenase activity; metal ion binding; chromatin binding; enzyme binding; histone demethylase activity; androgen receptor binding; zinc ion binding; histone H3-methyl-lysine-36 demethylase activity; GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; methylated histone binding;
Cellular component	nucleus; nucleoplasm; pericentric heterochromatin; histone methyltransferase complex;
Biological process	regulation of transcription by RNA polymerase II; regulation of transcription, DNA-templated; transcription, DNA-templated; positive regulation of cell population proliferation; blastocyst formation; regulation of gene expression; positive regulation of gene expression; histone H3-K9 demethylation; positive regulation of neuron differentiation; negative regulation of histone H3-K9 trimethylation; regulation of stem cell population maintenance; regulation of stem cell differentiation; histone H3-K36 demethylation; chromatin organization; negative regulation of transcription by RNA polymerase II; chromatin remodeling; stem cell population maintenance;
	Sources:Amigo / QuickGO
Orthologs
	23081
	76804
	ENSG00000107077
	ENSMUSG00000028397
	Q9H3R0
	Q8VCD7
NM_001146694; NM_001146695; NM_001146696; NM_001304339; NM_001304340;
	NM_001304341; NM_015061; NM_001353997; NM_001353998; NM_001353999; NM_001354000; NM_001354001
	NM_001172095; NM_144787; NM_001356561
NP_001140167; NP_001140168; NP_001291268; NP_001291269; NP_001291270;
	NP_055876; NP_001340926; NP_001340927; NP_001340928; NP_001340929; NP_001340930
	NP_001165566; NP_659036; NP_001343490
	Wikidata
View/Edit Human	View/Edit Mouse

Lysine-specific demethylase 4C is an enzyme that in humans is encoded by the KDM4C gene.^[5]^[6]^[7]

Function[]

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with one JmjC domain, one JmjN domain, two PHD-type zinc fingers, and two Tudor domains. This nuclear protein belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily. It functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form. Chromosomal aberrations and increased transcriptional expression of this gene are associated with esophageal squamous cell carcinoma.^[7] A expressional decrease of KDM4C was found during cardiac differentation of murine embryonic stem cells.^[8]

Model organisms[]

*Kdm4c* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Abnormal^[9]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Normal^[10]
Citrobacter infection	Normal^[11]
All tests and analysis from^[12]^[13]

Model organisms have been used in the study of KDM4C function. A conditional knockout mouse line, called Kdm4c^{tm1a(KOMP)Wtsi}^[14]^[15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[16]^[17]^[18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[12]^[19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.^[12] Homozygous mutant males had decreased haematocrit and haemoglobin levels, while animals of both sex displayed an increase in sebaceous gland size.^[12]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000107077 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028397 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Oct 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
^ Katoh M, Katoh M (Jun 2004). "Identification and characterization of JMJD2 family genes in silico". International Journal of Oncology. 24 (6): 1623–8. doi:10.3892/ijo.25.3.759. PMID 15138608.
^ ^a ^b "Entrez Gene: JMJD2C jumonji domain containing 2C".
^ Boeckel, Jes-Niels; Derlet, Anja; Glaser, Simone F.; Luczak, Annika; Lucas, Tina; Heumüller, Andreas W.; Krüger, Marcus; Zehendner, Christoph M.; Kaluza, David (July 2016). "JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 36 (7): 1425–1433. doi:10.1161/ATVBAHA.116.307695. ISSN 1524-4636. PMID 27199445.
^ "Haematology data for Kdm4c". Wellcome Trust Sanger Institute.
^ "Salmonella infection data for Kdm4c". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Kdm4c". Wellcome Trust Sanger Institute.
^ ^a ^b ^c ^d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ "International Knockout Mouse Consortium".
^ "Mouse Genome Informatics".
^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading[]

Yang ZQ, Imoto I, Fukuda Y, Pimkhaokham A, Shimada Y, Imamura M, Sugano S, Nakamura Y, Inazawa J (Sep 2000). "Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines". Cancer Research. 60 (17): 4735–9. PMID 10987278.
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y (May 2006). "Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell. 125 (3): 467–81. doi:10.1016/j.cell.2006.03.028. PMID 16603238. S2CID 14461740.
Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T, Hansen KH, Helin K (Jul 2006). "The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3". Nature. 442 (7100): 307–11. Bibcode:2006Natur.442..307C. doi:10.1038/nature04837. PMID 16732293. S2CID 2874903.
Wissmann M, Yin N, Müller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R, Günther T, Buettner R, Metzger E, Schüle R (Mar 2007). "Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression". Nature Cell Biology. 9 (3): 347–53. doi:10.1038/ncb1546. PMID 17277772. S2CID 26006234.
Katoh Y, Katoh M (Aug 2007). "Comparative integromics on JMJD2A, JMJD2B and JMJD2C: preferential expression of JMJD2C in undifferentiated ES cells". International Journal of Molecular Medicine. 20 (2): 269–73. doi:10.3892/ijmm.20.2.269. PMID 17611647.
Erhu Zhao, Jane Ding,.....Hongjuan Cui, Han-Fei Ding (2016). "KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism". Cell Reports. 14 (3): 506–519. doi:10.1016/j.celrep.2015.12.053. PMC 4731315. PMID 26774480.CS1 maint: uses authors parameter (link)

This article on a gene on human chromosome 9 is a stub. You can help Wikipedia by .

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000107077 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028397 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9872452-5] Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Oct 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.

[pmid15138608-6] Katoh M, Katoh M (Jun 2004). "Identification and characterization of JMJD2 family genes in silico". International Journal of Oncology. 24 (6): 1623–8. doi:10.3892/ijo.25.3.759. PMID 15138608.

[entrez-7] "Entrez Gene: JMJD2C jumonji domain containing 2C".

[8] Boeckel, Jes-Niels; Derlet, Anja; Glaser, Simone F.; Luczak, Annika; Lucas, Tina; Heumüller, Andreas W.; Krüger, Marcus; Zehendner, Christoph M.; Kaluza, David (July 2016). "JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 36 (7): 1425–1433. doi:10.1161/ATVBAHA.116.307695. ISSN 1524-4636. PMID 27199445.

[Haematology-9] "Haematology data for Kdm4c". Wellcome Trust Sanger Institute.

[''Salmonella''_infection-10] "Salmonella infection data for Kdm4c". Wellcome Trust Sanger Institute.

[''Citrobacter''_infection-11] "Citrobacter infection data for Kdm4c". Wellcome Trust Sanger Institute.

[mgp_reference-12] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.

[13] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-14] "International Knockout Mouse Consortium".

[mgi_allele_ref-15] "Mouse Genome Informatics".

[pmid21677750-16] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-17] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-18] Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.

[pmid21722353-19] van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

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v t Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
1.14.11: 2-oxoglutarate	Prolyl hydroxylase HIF prolyl-hydroxylase EGLN1 EGLN2 EGLN3 P4HTM 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 14α-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 Ecdysone 20-monooxygenase Deoxyhypusine monooxygenase

v t Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)