2jrz

Structural highlights

Disease

[JAD1C_HUMAN] Defects in KDM5C are the cause of mental retardation, X-linked, syndromic, Claes-Jensen type (MRXSCJ) [MIM:300534]. A disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. MRXSCJ patients manifest mental retardation associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism.^{[1] [2] [3] [4] [5]}

Function

[JAD1C_HUMAN] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements.^{[6] [7] [8]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 2007 Mar 23;128(6):1077-88. Epub 2007 Feb 22. PMID:17320160 doi:10.1016/j.cell.2007.02.017
2. ↑ Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A, Shi Y. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature. 2007 May 31;447(7144):601-5. Epub 2007 Apr 29. PMID:17468742 doi:nature05823
3. ↑ Jensen LR, Amende M, Gurok U, Moser B, Gimmel V, Tzschach A, Janecke AR, Tariverdian G, Chelly J, Fryns JP, Van Esch H, Kleefstra T, Hamel B, Moraine C, Gecz J, Turner G, Reinhardt R, Kalscheuer VM, Ropers HH, Lenzner S. Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. Am J Hum Genet. 2005 Feb;76(2):227-36. Epub 2004 Dec 7. PMID:15586325 doi:10.1086/427563
4. ↑ Santos C, Rodriguez-Revenga L, Madrigal I, Badenas C, Pineda M, Mila M. A novel mutation in JARID1C gene associated with mental retardation. Eur J Hum Genet. 2006 May;14(5):583-6. PMID:16538222 doi:5201608
5. ↑ Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR. Novel JARID1C/SMCX mutations in patients with X-linked mental retardation. Hum Mutat. 2006 Apr;27(4):389. PMID:16541399 doi:10.1002/humu.9420
6. ↑ Christensen J, Agger K, Cloos PA, Pasini D, Rose S, Sennels L, Rappsilber J, Hansen KH, Salcini AE, Helin K. RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell. 2007 Mar 23;128(6):1063-76. Epub 2007 Feb 22. PMID:17320161 doi:S0092-8674(07)00182-1
7. ↑ Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 2007 Mar 23;128(6):1077-88. Epub 2007 Feb 22. PMID:17320160 doi:10.1016/j.cell.2007.02.017
8. ↑ Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A, Shi Y. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature. 2007 May 31;447(7144):601-5. Epub 2007 Apr 29. PMID:17468742 doi:nature05823
9. ↑ Koehler C, Bishop S, Dowler EF, Schmieder P, Diehl A, Oschkinat H, Ball LJ. Backbone and sidechain 1H, 13C and 15N resonance assignments of the Bright/ARID domain from the human JARID1C (SMCX) protein. Biomol NMR Assign. 2008 Jun;2(1):9-11. Epub 2007 Dec 8. PMID:19636912 doi:10.1007/s12104-007-9071-7