JARID1A

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Lysine (K)-specific demethylase 5A
Protein KDM5A PDB 2JXJ.png
Rendering based on PDB 2JXJ.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KDM5A ; RBBP-2; RBBP2; RBP2
External IDs OMIM180202 MGI2136980 HomoloGene3419 GeneCards: KDM5A Gene
RNA expression pattern
PBB GE JARID1A 215698 at tn.png
PBB GE JARID1A 202040 s at tn.png
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:
0.39 – 0.5 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.[1][2]

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.[2]

The Drosophila homolog, LID, was found to be an H3K4 histone demethylase that binds to c-Myc.[3] It was recently renamed to Lysine Demethylase 5A (KDM5A).

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

Interactions[edit]

JARID1A has been shown to interact with Estrogen receptor alpha,[4] LMO2[5] and Retinoblastoma protein.[4][6]

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]

References[edit]

  1. ^ Defeo-Jones D, Huang PS, Jones RE, Haskell KM, Vuocolo GA, Hanobik MG, Huber HE, Oliff A (August 1991). "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product". Nature 352 (6332): 251–4. doi:10.1038/352251a0. PMID 1857421. 
  2. ^ a b "Entrez Gene: JARID1A jumonji, AT rich interactive domain 1A". 
  3. ^ Secombe J, Li L, Carlos L, Eisenman RN (2007). "The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth". Genes Dev. 21 (5): 537–51. doi:10.1101/gad.1523007. PMC 1820896. PMID 17311883. 
  4. ^ a b Chan, S W; Hong W (July 2001). "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription". J. Biol. Chem. (United States) 276 (30): 28402–12. doi:10.1074/jbc.M100313200. ISSN 0021-9258. PMID 11358960. 
  5. ^ Mao, S; Neale G A; Goorha R M (April 1997). "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2". Oncogene (ENGLAND) 14 (13): 1531–9. doi:10.1038/sj.onc.1200988. ISSN 0950-9232. PMID 9129143. 
  6. ^ Kim, Y W; Otterson G A; Kratzke R A; Coxon A B; Kaye F J (November 1994). "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein". Mol. Cell. Biol. (UNITED STATES) 14 (11): 7256–64. ISSN 0270-7306. PMC 359260. PMID 7935440. 

Further reading[edit]

External links[edit]

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