KDM5A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JXJ, 2KGG, 2KGI, 3GL6, 5C11, 5E6H, 5IWF, 5IVV, 5ISL, 5CEH, 5IVB
Identifiers
Aliases	KDM5A, RBBP-2, RBBP2, RBP2, JARID1A, lysine demethylase 5A
External IDs	OMIM: 180202 MGI: 2136980 HomoloGene: 3419 GeneCards: KDM5A
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.33 Start 280,057 bp[1] End 389,320 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 F1|6 56.95 cM Start 120,341,085 bp[2] End 120,421,535 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in caput epididymis optic nerve nipple corpus epididymis saphenous vein spongy bone pericardium superior surface of tongue trigeminal ganglion pylorus Top expressed in medullary collecting duct pineal gland left lung lobe internal carotid artery atrioventricular valve external carotid artery seminal vesicula dermis median eminence atrium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding transcription coactivator activity chromatin binding dioxygenase activity metal ion binding protein binding oxidoreductase activity chromatin DNA binding histone demethylase activity core promoter sequence-specific DNA binding DNA-binding transcription factor activity histone H3-methyl-lysine-9 demethylase activity histone H3-tri/di/monomethyl-lysine-4 demethylase activity zinc ion binding methylated histone binding histone binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription repressor activity, RNA polymerase II-specific Cellular component cyclin-dependent protein kinase activating kinase holoenzyme complex nucleoplasm protein-DNA complex nucleolus nucleus histone methyltransferase complex Biological process male gonad development regulation of transcription, DNA-templated rhythmic process negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II circadian regulation of gene expression transcription, DNA-templated positive regulation of transcription, DNA-templated multicellular organism development spermatogenesis negative regulation of histone deacetylase activity histone H3-K9 demethylation histone H3-K4 demethylation histone H3-K4 demethylation, trimethyl-H3-K4-specific regulation of DNA-binding transcription factor activity chromatin organization chromatin remodeling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5927 214899 Ensembl ENSG00000073614 ENSMUSG00000030180 UniProt P29375 Q3UXZ9 RefSeq (mRNA) NM_005056 NM_001042603 NM_145997 RefSeq (protein) NP_001036068 NP_666109 Location (UCSC) Chr 12: 0.28 – 0.39 Mb Chr 6: 120.34 – 120.42 Mb PubMed search [3] [4]
Wikidata
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Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.^[5][6]

Function

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 formerly 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.^[6]

The Drosophila homolog, LID, was found to be an H3K4 histone demethylase that binds to c-Myc.^[7] It was recently renamed to Lysine Demethylase 5 (KDM5).

Enzymatically can be designated as a trimethyllysine dioxygenase, which is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily (EC 1.14.11.8).

Interactions

JARID1A has been shown to interact with Estrogen receptor alpha,^[8] LMO2^[9] and Retinoblastoma protein.^[8][10]

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.^[11][12]

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.^[13]