KDM5A

Lysine (K)-specific demethylase 5A
Rendering based on PDB 2JXJ.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2JXJ, 2KGG, 2KGI, 3GL6
Identifiers
Symbols	KDM5A ; RBBP-2; RBBP2; RBP2
External IDs	OMIM: 180202 MGI: 2136980 HomoloGene: 3419 GeneCards: KDM5A Gene
Gene ontology Molecular function • DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • transcription coactivator activity • protein binding • zinc ion binding • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors Cellular component • nucleus • nucleoplasm • nucleolus • cytoplasm • cyclin-dependent protein kinase activating kinase holoenzyme complex Biological process • chromatin organization • transcription from RNA polymerase II promoter • multicellular organismal development • chromatin modification • circadian regulation of gene expression • positive regulation of transcription, DNA-templated • oxidation-reduction process • negative regulation of histone deacetylase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5927	214899
Ensembl	ENSG00000073614	ENSMUSG00000030180
UniProt	P29375	Q3UXZ9
RefSeq (mRNA)	NM_001042603	NM_145997
RefSeq (protein)	NP_001036068	NP_666109
Location (UCSC)	Chr 12: 0.28 – 0.39 Mb	Chr 6: 120.36 – 120.44 Mb
PubMed search	[1]	[2]

Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.

The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein which regulates cell proliferation. It was formally known as Retinoblastoma Binding Protein 2 (RBP2). This protein also interacts with rhombotin-2 which functions distinctly in erythropoiesis and in T-cell leukemogenesis. Rhombotin-2 is thought to either directly affect the activity of the encoded protein or may indirectly modulate the functions of the retinoblastoma protein by binding to this protein. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

The Drosophila homolog, LID, was found to be an H3K4 histone demethylase that binds to c-Myc. It was recently renamed to Lysine Demethylase 5A (KDM5A).

Enzymatically can be designated as a trimethyllysine dioxygenase. (EC 1.14.11.8)

Interactions

JARID1A has been shown to interact with Estrogen receptor alpha, LMO2 and Retinoblastoma protein.

JARID1A is a major component of the circadian clock, the upregulation of which at the end of the sleep phase blocks HDAC1 activity. Blocking HDAC1 activity results in an upregulation of CLOCK and BMAL1 and consequent upregulation of PER proteins. The PSF (polypyrimidine tract-binding protein-associated splicing factor) within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription.[PMID 21960634] [PMID 21680841]

Knockdown of JARID1A promoted osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo and resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the H3K4me3 mark by chromatin immunoprecipitation assays. RBP2 was also physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of human adipose-derived stromal cells. [PMID 21604327]

Further reading

• Kim YW, Otterson GA, Kratzke RA, et al. (1994). "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein.". Mol. Cell. Biol. 14 (11): 7256–64. PMC 359260. PMID 7935440. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Fattaey AR, Helin K, Dembski MS, et al. (1993). "Characterization of the retinoblastoma binding proteins RBP1 and RBP2". Oncogene 8 (11): 3149–56. PMID 8414517. 
• Baens M, Aerssens J, van Zand K, et al. (1996). "Isolation and regional assignment of human chromosome 12p cDNAs". Genomics 29 (1): 44–52. doi:10.1006/geno.1995.1213. PMID 8530100. 
• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
• Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549. 
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. 
• Mao S, Neale GA, Goorha RM (1997). "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2". Oncogene 14 (13): 1531–9. doi:10.1038/sj.onc.1200988. PMID 9129143. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• Chan SW, Hong W (2001). "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription". J. Biol. Chem. 276 (30): 28402–12. doi:10.1074/jbc.M100313200. PMID 11358960. 
• Sandrock B, Egly JM (2001). "A yeast four-hybrid system identifies Cdk-activating kinase as a regulator of the XPD helicase, a subunit of transcription factor IIH". J. Biol. Chem. 276 (38): 35328–33. doi:10.1074/jbc.M105570200. PMID 11445587. 
• 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): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. 
• Benevolenskaya EV, Murray HL, Branton P, et al. (2005). "Binding of pRB to the PHD protein RBP2 promotes cellular differentiation". Mol. Cell 18 (6): 623–35. doi:10.1016/j.molcel.2005.05.012. PMID 15949438. 
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560. 
• Tzschach A, Lenzner S, Moser B, et al. (2006). "Novel JARID1C/SMCX mutations in patients with X-linked mental retardation". Hum. Mutat. 27 (4): 389. doi:10.1002/humu.9420. PMID 16541399. 
• Roesch A, Becker B, Schneider-Brachert W, et al. (2006). "Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells". J. Invest. Dermatol. 126 (8): 1850–9. doi:10.1038/sj.jid.5700324. PMID 16645588. 
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. 

External links

• JARID1A protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.