KDM5A (Jumonji, AT rich interactive domain 1A (RBBP2-like))

2006-04-01   Laura J.C.M. van Zutven , Anne R.M. von Bergh 

Afdeling Klinische Genetica, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

Identity

HGNC
LOCATION
12p13.33
LOCUSID
ALIAS
RBBP-2,RBBP2,RBP2
FUSION GENES

DNA/RNA

Description

31 exons over 105 kb

Transcription

from centromere to telomere, yielding mRNA of 6,5 kb

Proteins

Atlas Image

Description

JARID1A (Jumonji, AT-rich interactive domain 1A) encodes the 196 kDa retinoblastoma binding protein 2 (1722 amino acids). It contains several motifs, including a leucine-X-cysteine-X-glutamic acid (LXCXE) motif, which is important for association with the T/E1A pocket domain of the retinoblastoma protein. Additionally, the protein contains ARID, Jumonji, and 3 PHD (LAP) domains, which are frequent in proteins regulating transcription through changes in chromatin structure.

Expression

Widely expressed

Localisation

Nuclear

Function

Probably in regulating transcription through changes in chromatin structure

Homology

RBP2 homologue 1 (RBP2-H1)

Implicated in

Note
Only one case to date, a 1- year-old boy
Prognosis
Patient reached complete remission and remains in complete remission (CR) for at least 5 years
Cytogenetics
complex/variant t(11;12)(p15;p13); i.e. t(11;21;12)(p15;p13;p13), but misdiagnosed as add(11)(p15) and der(21)t(11;21)(p15;p13). Chromosome 12 was cytogenetically normal by conventional banding techniques and only identified as a partner in this translocation after FISH.
Hybrid gene
5 NUP98 - 3 JARID1A, including the first 13 exons of NUP98 and exons 28-31 of JARID1A
Atlas Image
Fusion protein
The NUP98-JARID1A fusion protein contains the Phe-Gly (FG) repeats of the N-terminal part of NUP98. The JARID1A sequence starting with exon 28 still contains the sequence encoding the C-terminal PHD domain.

Bibliography

Pubmed IDLast YearTitleAuthors
159494382005Binding of pRB to the PHD protein RBP2 promotes cellular differentiation.Benevolenskaya EV et al
79354401994Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein.Kim YW et al
164190552006Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene.van Zutven LJ et al

Other Information

Locus ID:

NCBI: 5927
MIM: 180202
HGNC: 9886
Ensembl: ENSG00000073614

Variants:

dbSNP: 5927
ClinVar: 5927
TCGA: ENSG00000073614
COSMIC: KDM5A

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000073614ENST00000399788P29375
ENSG00000073614ENST00000535014F5GZ99
ENSG00000073614ENST00000536014F5H322
ENSG00000073614ENST00000543507F5GZR8
ENSG00000073614ENST00000544760E7EV89

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
HDMs demethylate histonesREACTOMER-HSA-3214842

References

Pubmed IDYearTitleCitations
173201612007RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3.207
194304642009Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.160
187221782008Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation.70
226153822012H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.61
198500452010The histone demethylase RBP2 Is overexpressed in gastric cancer and its inhibition triggers senescence of cancer cells.59
175737802007RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation.50
237225412013Histone demethylase RBP2 promotes lung tumorigenesis and cancer metastasis.45
245829652014Histone demethylase RBP2 is critical for breast cancer progression and metastasis.39
182705112008The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC motif.35
256867482015Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism.34

Citation

Laura J.C.M. van Zutven ; Anne R.M. von Bergh

KDM5A (Jumonji, AT rich interactive domain 1A (RBBP2-like))

Atlas Genet Cytogenet Oncol Haematol. 2006-04-01

Online version: http://atlasgeneticsoncology.org/gene/41033/kdm5a