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Gene Review:

CRB2 - crumbs family member 2

Homo sapiens

Synonyms: Crumbs-like protein 2, FLJ16786, FLJ38464, Protein crumbs homolog 2

van den Hurk, J.A. et al., Saka, Y. et al., Botuyan, M.V. et al., Richard, M. et al., Katoh, M. et al., et al.

Richard, Roepman, Aartsen, van Rossum, den Hollander, Knust, Wijnholds, Cremers,

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High impact information on CRB2

Using X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, we show that, despite low amino acid sequence conservation, both 53BP1 and Crb2 contain tandem tudor domains that interact with histone H4 specifically dimethylated at Lys20 (H4-K20me2) [1].
Upon UV damage, Crb2 is transiently modified, probably phosphorylated, with a similar timing of phosphorylation in Chk1 kinase, which is reported to restrain Cdc2 activation [2].
Cut5, Crb2, and Chk1 thus may form a checkpoint sensor-transmitter pathway to arrest the cell cycle [2].
Moreover, moderate overexpression of Chk1 suppresses the phenotypes of cut5 and crb2 mutants [2].
Here we report that Cut5 interacts with a novel checkpoint protein Crb2 and that this interaction is needed for normal genome maintenance [2].

Biological context of CRB2

CRB2 gene was found to encode transmembrane protein as well as secreted protein due to alternative splicing [3].
Here, we identified and characterized a novel Crumbs family gene, Crumbs homolog 2 (CRB2), by using bioinformatics [3].
It is possible that a more complex clinical phenotype is associated with the loss or altered function of CRB2 in humans due to its expression in tissues other than the retina [4].
RESULTS: The CRB2 gene consists of 13 exons and encodes a 1285 amino acid transmembrane protein [4].
Mutation analysis of the CRB2 gene revealed 11 sequence variants leading to an amino acid substitution [4].

Associations of CRB2 with chemical compounds

Moreover, spset1 allows recovery specifically of the crb2 checkpoint mutant upon treatment with the replication inhibitor hydroxyurea but not upon UV irradiation [5].

Other interactions of CRB2

Human CRB1 and its two paralogues, CRB2 and CRB3, are highly conserved throughout the animal kingdom [6].
The open reading frame and splice junctions of CRB2 were analyzed for mutations by single-strand conformation analysis and direct nucleotide sequencing in 85 RP patients and 79 LCA patients [4].

Analytical, diagnostic and therapeutic context of CRB2

METHODS: The CRB2 mRNA and its expression pattern in human tissues were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) [4].

References

Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair. Botuyan, M.V., Lee, J., Ward, I.M., Kim, J.E., Thompson, J.R., Chen, J., Mer, G. Cell (2006) [Pubmed]
Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1. Saka, Y., Esashi, F., Matsusaka, T., Mochida, S., Yanagida, M. Genes Dev. (1997) [Pubmed]
Identification and characterization of Crumbs homolog 2 gene at human chromosome 9q33.3. Katoh, M., Katoh, M. Int. J. Oncol. (2004) [Pubmed]
Characterization of the Crumbs homolog 2 (CRB2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis. van den Hurk, J.A., Rashbass, P., Roepman, R., Davis, J., Voesenek, K.E., Arends, M.L., Zonneveld, M.N., van Roekel, M.H., Cameron, K., Rohrschneider, K., Heckenlively, J.R., Koenekoop, R.K., Hoyng, C.B., Cremers, F.P., den Hollander, A.I. Mol. Vis. (2005) [Pubmed]
The fission yeast spSet1p is a histone H3-K4 methyltransferase that functions in telomere maintenance and DNA repair in an ATM kinase Rad3-dependent pathway. Kanoh, J., Francesconi, S., Collura, A., Schramke, V., Ishikawa, F., Baldacci, G., Géli, V. J. Mol. Biol. (2003) [Pubmed]
Towards understanding CRUMBS function in retinal dystrophies. Richard, M., Roepman, R., Aartsen, W.M., van Rossum, A.G., den Hollander, A.I., Knust, E., Wijnholds, J., Cremers, F.P. Hum. Mol. Genet. (2006) [Pubmed]

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