PTHR10603

FRAGILE X MENTAL RETARDATION SYNDROME-RELATED PROTEIN

PANTHER entry
Member databasePANTHER
PANTHER typefamily

Description
Imported from IPR040148

Fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), and its paralogues, FXR1 and FXR2 (RNA-binding protein FXR1 and 2, respectively), comprise a family of RNA-binding proteins
[9]
. They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box
[3]
.

FMR1 protein is a multifunctional polyribosome-associated protein that plays a central role in neuronal development and synaptic plasticity. It regulates alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs
[4, 6, 1]
. FMR1 is thought to bind target mRNA in the nucleus to form a ribonucleoprotein complex which is transported to dendrites and spines
[12]
. It is also required for ovary development and function
[5]
. FMR1 has also been shown to interact with components of the miRNA pathway
[10]
. A large expansion of the CGG trinucleotide repeat in the 5'-untranslated region of the FMR1 gene causes Fragile X syndrome (FXS), an inherited developmental disorder that causes a broad range of intellectual and physical challenges
[8]
.

FXR1 and FXR2 interact with FMR1 and seem to have a related role; therefore they are likely to play important roles in the function of FMR1 and in the pathogenesis of the FXS syndrome
[7, 11]
. FXR1 is highly expressed in vertebrates muscle cells and is required for proper development of this tissue
[13, 2]
.

References
Imported from IPR040148

1.MOV10 and FMRP regulate AGO2 association with microRNA recognition elements. Kenny PJ, Zhou H, Kim M, Skariah G, Khetani RS, Drnevich J, Arcila ML, Kosik KS, Ceman S. Cell Rep 9, 1729-1741, (2014). View articlePMID: 25464849

2.Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy. Estan MC, Fernandez-Nunez E, Zaki MS, Esteban MI, Donkervoort S, Hawkins C, Caparros-Martin JA, Saade D, Hu Y, Bolduc V, Chao KR, Nevado J, Lamuedra A, Largo R, Herrero-Beaumont G, Regadera J, Hernandez-Chico C, Tizzano EF, Martinez-Glez V, Carvajal JJ, Zong R, Nelson DL, Otaify GA, Temtamy S, Aglan M, Issa M, Bonnemann CG, Lapunzina P, Yoon G, Ruiz-Perez VL. Nat Commun 10, 797, (2019). PMID: 30770808

3.Human FMRP contains an integral tandem Agenet (Tudor) and KH motif in the amino terminal domain. Myrick LK, Hashimoto H, Cheng X, Warren ST. Hum. Mol. Genet. 24, 1733-40, (2015). View articlePMID: 25416280

4.Fragile X syndrome. Hagerman RJ, Berry-Kravis E, Hazlett HC, Bailey DB Jr, Moine H, Kooy RF, Tassone F, Gantois I, Sonenberg N, Mandel JL, Hagerman PJ. Nat Rev Dis Primers 3, 17065, (2017). View articlePMID: 28960184

5.Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins. Greenblatt EJ, Spradling AC. Science 361, 709-712, (2018). View articlePMID: 30115809

6.Modeling Fragile X Syndrome in Drosophila. Drozd M, Bardoni B, Capovilla M. Front Mol Neurosci 11, 124, (2018). View articlePMID: 29713264

7.The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. Zhang Y, O'Connor JP, Siomi MC, Srinivasan S, Dutra A, Nussbaum RL, Dreyfuss G. EMBO J. 14, 5358-66, (1995). PMID: 7489725

8.Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP. Cell 65, 905-14, (1991). View articlePMID: 1710175

9.Structural studies of the tandem Tudor domains of fragile X mental retardation related proteins FXR1 and FXR2. Adams-Cioaba MA, Guo Y, Bian C, Amaya MF, Lam R, Wasney GA, Vedadi M, Xu C, Min J. PLoS ONE 5, e13559, (2010). View articlePMID: 21072162

10.Macro role(s) of microRNAs in fragile X syndrome? Li X, Jin P. Neuromolecular Med. 11, 200-7, (2009). View articlePMID: 19669947

11.FXR1, an autosomal homolog of the fragile X mental retardation gene. Siomi MC, Siomi H, Sauer WH, Srinivasan S, Nussbaum RL, Dreyfuss G. EMBO J. 14, 2401-8, (1995). PMID: 7781595

12.Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Bassell GJ, Warren ST. Neuron 60, 201-14, (2008). View articlePMID: 18957214

13.Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo. Mientjes EJ, Willemsen R, Kirkpatrick LL, Nieuwenhuizen IM, Hoogeveen-Westerveld M, Verweij M, Reis S, Bardoni B, Hoogeveen AT, Oostra BA, Nelson DL. Hum. Mol. Genet. 13, 1291-302, (2004). View articlePMID: 15128702

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