D
IPR047495

RNA-binding protein FXR1, second type I K homology domain

InterPro entry
Short nameKH_I_FXR1_rpt2
Overlapping
homologous
superfamilies
 
domain relationships

Description

FXR1 contains three K-homology (KH) RNA-binding domains, the second one is represented in this entry.

FXR1 is one of the autosomal paralogues of fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), part of a family of RNA-binding proteins
[2]
. These proteins associate with polyribosomes, and play a central role in neuronal development and synaptic plasticity. They recognize methylated lysine and bind H4K20me1/2/3 through their Tudor-like Agenet domains and they are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS)
[4, 8, 2, 7, 6, 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
[4]
. The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association.

FXR1 interacts with FXR2 and FMR1. FXR1 is highly expressed in muscle cells and is required for proper development of this tissue. It may regulate intracellular transport and local translation of certain mRNAs
[1, 3, 5]
.

References

1.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

2.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

3.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

4.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

5.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

6.Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. Siomi MC, Zhang Y, Siomi H, Dreyfuss G. Mol Cell Biol 16, 3825-32, (1996). PMID: 8668200

7.Evidence that fragile X mental retardation protein is a negative regulator of translation. Laggerbauer B, Ostareck D, Keidel EM, Ostareck-Lederer A, Fischer U. Hum Mol Genet 10, 329-38, (2001). PMID: 11157796

8.New World and Old World Alphaviruses Have Evolved to Exploit Different Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral Replication Complexes. Kim DY, Reynaud JM, Rasalouskaya A, Akhrymuk I, Mobley JA, Frolov I, Frolova EI. PLoS Pathog 12, e1005810, (2016). PMID: 27509095

9.RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by reducing Noggin expression. Guo W, Zhang L, Christopher DM, Teng ZQ, Fausett SR, Liu C, George OL, Klingensmith J, Jin P, Zhao X. Neuron 70, 924-38, (2011). PMID: 21658585

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