KDM5A

Last updated
KDM5A
Protein KDM5A PDB 2JXJ.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases KDM5A , RBBP-2, RBBP2, RBP2, JARID1A, lysine demethylase 5A
External IDs OMIM: 180202 MGI: 2136980 HomoloGene: 3419 GeneCards: KDM5A
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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
View/Edit Human View/Edit Mouse

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]

Related Research Articles

Protein c-Fos Mammalian protein found in Homo sapiens

Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.

RUNX2 Protein-coding gene in the species Homo sapiens

Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the RUNX2 gene. RUNX2 is a key transcription factor associated with osteoblast differentiation.

Demethylases are enzymes that remove methyl (CH3-) groups from nucleic acids, proteins (in particular histones), and other molecules. Demethylase enzymes are important in epigenetic modification mechanisms. The demethylase proteins alter transcriptional regulation of the genome by controlling the methylation levels that occur on DNA and histones and, in turn, regulate the chromatin state at specific gene loci within organisms.

PHD finger

The PHD finger was discovered in 1993 as a Cys4-His-Cys3 motif in the plant homeodomain proteins HAT3.1 in Arabidopsis and maize ZmHox1a. The PHD finger motif resembles the metal binding RING domain (Cys3-His-Cys4) and FYVE domain. It occurs as a single finger, but often in clusters of two or three, and it also occurs together with other domains, such as the chromodomain and the bromodomain.

HDAC1

Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.

RUNX1 Protein-coding gene in the species Homo sapiens

Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the RUNX1 gene.

HDAC3

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.

Retinoblastoma-like protein 2 Protein-coding gene in the species Homo sapiens

Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene.

RBBP4

Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.

LMO2

LIM domain only 2, also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2 gene.

Retinoblastoma-like protein 1 Mammalian protein found in Homo sapiens

Retinoblastoma-like 1 (p107), also known as RBL1, is a protein that in humans is encoded by the RBL1 gene.

PRDM2 Protein-coding gene in the species Homo sapiens

PR domain zinc finger protein 2 is a protein that in humans is encoded by the PRDM2 gene.

KDM4A Lysine-specific demethylase 4A is an enzyme that in humans is encoded by the Kdm4a gene

Lysine-specific demethylase 4A is an enzyme that in humans is encoded by the KDM4A gene.

ARID4A Protein-coding gene in the species Homo sapiens

AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.

KDM5C Protein-coding gene in the species Homo sapiens

Lysine-specific demethylase 5C is an enzyme that in humans is encoded by the KDM5C gene. KDM5C belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.

JARID1B Protein-coding gene in the species Homo sapiens

Lysine-specific demethylase 5B also known as histone demethylase JARID1B is a demethylase enzyme that in humans is encoded by the KDM5B gene. JARID1B belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.

JARID2 Protein-coding gene in the species Homo sapiens

Protein Jumonji is a protein that in humans is encoded by the JARID2 gene. JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.

miR-137

In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.

SHOX2 Protein-coding gene in the species Homo sapiens

Short-stature homeobox 2, also known as homeobox protein Og12X or paired-related homeobox protein SHOT, is a protein that in humans is encoded by the SHOX2 gene.

Retinoblastoma protein Mammalian protein found in Homo sapiens

The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000073614 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030180 - 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.
  5. Defeo-Jones D, Huang PS, Jones RE, Haskell KM, Vuocolo GA, Hanobik MG, Huber HE, Oliff A (Jul 1991). "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product". Nature. 352 (6332): 251–4. Bibcode:1991Natur.352..251D. doi:10.1038/352251a0. PMID   1857421. S2CID   4357523.
  6. 1 2 "Entrez Gene: JARID1A jumonji, AT rich interactive domain 1A".
  7. Secombe J, Li L, Carlos L, Eisenman RN (Mar 2007). "The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth". Genes & Development. 21 (5): 537–51. doi:10.1101/gad.1523007. PMC   1820896 . PMID   17311883.
  8. 1 2 Chan SW, Hong W (Jul 2001). "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription". The Journal of Biological Chemistry. 276 (30): 28402–12. doi: 10.1074/jbc.M100313200 . PMID   11358960.
  9. Mao S, Neale GA, Goorha RM (Apr 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.
  10. Kim YW, Otterson GA, Kratzke RA, Coxon AB, Kaye FJ (Nov 1994). "Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein". Molecular and Cellular Biology. 14 (11): 7256–64. doi:10.1128/mcb.14.11.7256. PMC   359260 . PMID   7935440.
  11. DiTacchio L, Le HD, Vollmers C, Hatori M, Witcher M, Secombe J, Panda S (2011). "Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock". Science. 333 (6051): 1881–5. Bibcode:2011Sci...333.1881D. doi:10.1126/science.1206022. PMC   3204309 . PMID   21960634.
  12. Duong HA, Robles MS, Knutti D, Weitz CJ (2011). "A molecular mechanism for circadian clock negative feedback". Science. 332 (6036): 1436–9. Bibcode:2011Sci...332.1436D. doi:10.1126/science.1196766. PMC   3859310 . PMID   21680841.
  13. Ge W, Shi L, Zhou Y, Liu Y, Ma GE, Jiang Y, Xu Y, Zhang X, Feng H (2011). "Inhibition of osteogenic differentiation of human adipose-derived stromal cells by retinoblastoma binding protein 2 repression of RUNX2-activated transcription". Stem Cells. 29 (7): 1112–25. doi: 10.1002/stem.663 . PMID   21604327. S2CID   41977627.

Further reading

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