Disease relevance of FXR2

• Thus, a dominant negative effect of abnormal multimeric protein complexes lacking FMRP (e.g. by modification of FXR1 and FXR2 protein functions) may result in the fragile X syndrome phenotype [1].
• Cloning and characterization of the novel chimeric gene p53/FXR2 in the acute megakaryoblastic leukemia cell line CMK11-5 [2].
• The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins [3].

Psychiatry related information on FXR2

• Disruption of Fxr2 in mice produces learning and memory deficits, and Fmr1 and Fxr2 double-knockout mice have exaggerated impairments in certain neurobehavioral phenotypes relative to the single gene knockouts [4].

High impact information on FXR2

• The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2 [5].
• The FXR2 gene is located on human chromosome 17 at 17p13 [5].
• Two homologs of FMRP have been identified, FXR1P and FXR2P [6].
• Given the behavioral phenotype in fragile X patients and the phenotype previously reported for the Fmr1 knockout mouse, we performed a thorough evaluation of the Fxr2 knockout phenotype using a behavioral test battery [6].
• The findings implicate a role for Fxr2 in central nervous system function [6].

Biological context of FXR2

• All three genes are very well conserved from mouse to human, with identical exon sizes for all but two FXR2 exons [7].
• While the cDNA has two regions with similarity to the mouse double KH domain probe at the nucleotide level, there is no significant similarity of the amino acid sequence with human FMR1, FXR1 or FXR2, nor with KH amino acid motifs [8].
• The p53/FXR2 gene is the first reported p53 fusion gene [2].
• During routine BLAST sequence analysis it was discovered that this GC-rich region is highly related to the human fragile X-related protein 2 (FXR-2) 5'-untranslated RNA sequence [9].
• In support of this structure, the human ABP/SHBG and the FXR-2 genes map to the same site on chromosome 17 [9].

Anatomical context of FXR2

• To understand the regulation of the human FXR2 gene, we cloned the evolutionarily conserved region upstream of the FXR2 translation start site and showed that it also has bidirectional promoter activity in both neuronal and muscle cells as evidenced by luciferase reporter assay studies [4].
• Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis [10].
• FXR2 protein, which is closely related to FMRP, is also detected associated with mRNPs in translating polyribosomes [11].
• FXR1 and FXR2 mRNA had the same distribution and similar intensity in the brains of normal and pathologic fetuses (female and male carriers) [1].

Other interactions of FXR2

• Both FXR1 and FXR2 are autosomal gene homologues of FMR1 [12].

Analytical, diagnostic and therapeutic context of FXR2

• Western blot analyses have shown that the p53/FXR2 protein is indeed expressed in a Down syndrome-related acute megakaryoblastic leukemia cell line, CMK11-5 cells [2].
• By immunoblotting, we found that a marked reduction in FMRP levels is associated with a modest increase in FXR1P and no changes in FXR2P levels [13].

References