Disease relevance of FXR1

• The X-linked FMR1 gene, which is involved in the fragile X syndrome, forms a small gene family with its two autosomal homologs, FXR1 and FXR2 [1].
• Expression of the hamster cDNA clone in Escherichia coli and antibody production indicates unequivocally the location of the FXR1 protein in the cytoplasm of hamster cells [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 FXR1

• Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P [4].

High impact information on FXR1

• AGO2 and FXR1 bind to the AU-rich element in the 3'-UTR of TNFalpha mRNA, unexpectedly activating its translation in a cell growth-dependent manner [5].
• 1. In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1 [6].
• We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13 [7].
• Colocalization studies further showed that the FMRP-GFP labeled granules also contained RNA, ribosomal subunits, kinesin heavy chain, and FXR1P molecules [8].
• The failure of FMRP I304N to suppress translation is not due to its reduced affinity for mRNA or its interacting proteins FXR1 and FXR2 [9].

Biological context of FXR1

• The association of the FMR1, FXR1, and FXR2 proteins with ribosomes suggests they have functions in translation or mRNA stability [10].
• Alternative splicing in the murine and human FXR1 genes [11].
• Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis [12].
• Fmrp is expressed ubiquitously throughout the embryo during embryonic development, whereas Fxr1p shows a more tissue-specific expression particularly during late embryonic development [13].
• An intronless form of the FXR1 gene, either processed functional homologue or pseudogene was localized to 12q12 [14].

Anatomical context of FXR1

• In muscle tissues as well as in murine myoblastic cell lines induced to differentiate into myotubes, FXR1P78and P70isoforms are replaced by novel unpredicted isoforms of 81-84 kDa and a novel FXR1 exon splice variant was detected in muscle RNA [12].
• Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis [15].
• At 24 hpf, fxr1 and fxr2 transcripts show complex distribution patterns in somites [16].
• In addition, Fxr1p is also highly expressed in striated muscle tissue [13].
• FXR1 and FXR2 mRNA had the same distribution and similar intensity in the brains of normal and pathologic fetuses (female and male carriers) [17].

Associations of FXR1 with chemical compounds

• We investigated the intracellular distribution of various FXR1P isoforms with (iso-e and iso-f) and without (iso-d) the potential NoS in transfected COS cells treated with the nuclear export inhibitor leptomycin-B [3].

Physical interactions of FXR1

• FMRP is the archetype of a novel family of cytoplasmic RNA-binding proteins that includes FXR1P and FXR2P [18].

Other interactions of FXR1

• Mapping of the ATP11B gene and refined localization of the SOX2 and FXR1 genes to BTA1q33 [19].
• The fragile-X-related gene FXR1 is a human autoantigen processed during apoptosis [2].

Analytical, diagnostic and therapeutic context of FXR1

• An appropriate animal model to study in vivo gene function is essential to unravel the cellular function of the gene products FMRP, FXR1P and FXR2P, respectively [13].
• Northern blot analysis of the human FXR1 gene revealed an expression pattern of a housekeeping gene with stronger expression in muscle [14].
• RNA in situ hybridization to sections of mouse embryo and adult tissues has shown that during embryonic development the mouse FXR1 mRNA is expressed in different tissues, most prominent in skeletal muscle, the gonads and distinct regions of the central nervous system, and that the expression is restricted to proliferating cells [14].
• Affinity chromatography followed by immunofluorescence microscopy analysis and immunoblots demonstrated the presence of autoimmune IgGs to FXR1 in the scleroderma patient [2].
• Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes [4].

References