background:
Fragile X syndrome is the most frequent form of inherited mental retardation and is the result of transcriptional silencing of the FMR1 gene on the X chromosome. The FMR1 gene contains a distinct CpG dinucleotide repeat located in the 5' untranslated region of the gene. In fragile X syndrome this tandem repeat is substantially amplified and subjected to extensive methylation and enhanced transcriptional silencing. The FMR1 protein (or FMRP) is an RNA-binding protein that associates with polyribosomes and is a likely component of a messenger ribonuclear protein (mRNP) particle. It contains several features that are characteristics of RNA-binding proteins, including two hnRNPK homology (KH) domains and an RGG amino acid motif (RGG box). FMR1 localizes to both the nucleus and the cytoplasm and can also interact with two fragile X syndrome related factors, FXR1 and FXR2, which form heterodimers through their N-terminal coiled-coil domains. Since FMR1 contains both a nuclear localization signal and a nuclear export signal it is also implicated in the nucleocytoplasmic transport of mRNAs.
Function:
Translation repressor. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates translation repression (By similarity). RNA-binding protein that plays a role in intracellular RNA transport and in the regulation of translation of target mRNAs. Associated with polysomes. May play a role in the transport of mRNA from the nucleus to the cytoplasm. Binds strongly to poly(G), binds moderately to poly(U) but shows very little binding to poly(A) or poly(C).
Subunit:
Component of the CYFIP1-EIF4E-FMR1 complex which is composed of CYFIP, EIF4E and FMR1. Interacts with CYFIP1 and CYFIP2. The interaction with brain cytoplasmic RNA 1 (BC1) increases binding affinity for the CYFIP1-EIF4E complex in the brain (By similarity). Homooligomer. Found in a RNP granule complex with IGF2BP1. Directly interacts with SMN and TDRD3. Interacts with the SMN core complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Interacts with FXR1, FXR2, IGF2BP1, NUFIP1, NUFIP2, MCRS1 and RANBP9.
Subcellular Location:
Cytoplasm. Nucleus, nucleolus.
Tissue Specificity:
Highest levels found in neurons, brain, testis, placenta and lymphocytes. Also expressed in epithelial tissues and at very low levels in glial cells.
Post-translational modifications:
Phosphorylated on several serine residues.
DISEASE:
Defects in FMR1 are the cause of fragile X syndrome (FRAX) [MIM:300624]. Fragile X syndrome is a common genetic disease (has a prevalence of one in every 2000 children) which is characterized by moderate to severe mental retardation, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most fragile X syndrome patients results from an amplification of a CGG repeat region which is directly in front of the coding region.
Defects in FMR1 are the cause of fragile X tremor/ataxia syndrome (FXTAS) [MIM:300623]. In FXTAS, the expanded repeats range in size from 55 to 200 repeats and are referred to as 'premutations'. Full repeat expansions with greater than 200 repeats results in fragile X mental retardation syndrome [MIM:300624]. Carriers of the premutation typically do not show the full fragile X syndrome phenotype, but comprise a subgroup that may have some physical features of fragile X syndrome or mild cognitive and emotional problems.
Defects in FMR1 are the cause of premature ovarian failure syndrome type 1 (POF1) [MIM:31172]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
Similarity:
Belongs to the FMR1 family.
Contains 2 Agenet-like domains.
Contains 2 KH domains.
Database links:
UniProtKB/Swiss-Prot: Q06787.1
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
脆性X综合症，又称马丁－贝尔综合症，是一种遗传疾病。该综合症可以导致一系列的特征性症状，包括生理、智力、情绪、以及行为上的异常。症状的轻重各有不同。该疾病伴随着X染色体上一个简单的三核苷酸基因序列（CGG）的扩增。这种扩增导致了一种称为FMR-1的蛋白质无法在病人体内表达，而该蛋白质是神经的正常发育必不可少的。
根据CGG重复序列的长度，目前普遍认可将脆性X综合症分为四种类型：正常人（含有19－31个CGG重复序列），前突变者（含有55－200个CGG重复序列），全突变者（含有200个以上的CGG重复序列），过渡型，又称“灰色区域型”（含有40－60个重复）。脆性X综合征这是一种导致智力低下的遗传疾病，是导致人群中智力低下的第二大病因——仅次于21三体综合症。
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