| Structural highlights
Disease
GGYF2_HUMAN Young adult-onset Parkinsonism. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Its association with Parkinson disease is however unclear. According to a number of studies, variations affecting this gene are not a frequent cause of Parkinson disease, suggesting that GIGYF2 does not play a major role in Parkinson disease etiology (PubMed:19279319, PubMed:19429085, PubMed:19638301, PubMed:19482505, PubMed:20004041, PubMed:19321232, PubMed:20060621).[1] [2] [3] [4] [5] [6] [7]
Function
GGYF2_HUMAN Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931). In 4EHP-GYF2 the complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (By similarity). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153).[UniProtKB:Q6Y7W8][8] [9]
Publication Abstract from PubMed
The GIGYF proteins interact with 4EHP and RNA-associated proteins to elicit transcript-specific translational repression. However, the mechanism by which the GIGYF1/2-4EHP complex is recruited to its target transcripts remain unclear. Here, we report the crystal structures of the GYF domains from GIGYF1 and GIGYF2 in complex with proline-rich sequences from the miRISC-binding proteins TNRC6C and TNRC6A, respectively. The TNRC6 proline-rich motifs bind to a conserved array of aromatic residues on the surface of the GIGYF1/2 GYF domains, thereby bridging 4EHP to Argonaute-miRNA complexes. Our structures also reveal a phenylalanine residue conserved from yeast to human GYF domains that contributes to GIGYF2 thermostability. The molecular details we outline here are likely to be conserved between GIGYF1/2 and other RNA-binding proteins to elicit 4EHP-mediated repression in different biological contexts.
Molecular basis for GIGYF-TNRC6 complex assembly.,Sobti M, Mead BJ, Stewart AG, Igreja C, Christie M RNA. 2023 Jun;29(6):724-734. doi: 10.1261/rna.079596.123. Epub 2023 Feb 28. PMID:36854607[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nichols WC, Kissell DK, Pankratz N, Pauciulo MW, Elsaesser VE, Clark KA, Halter CA, Rudolph A, Wojcieszek J, Pfeiffer RF, Foroud T. Variation in GIGYF2 is not associated with Parkinson disease. Neurology. 2009 Jun 2;72(22):1886-92. doi: 10.1212/01.wnl.0000346517.98982.1b., Epub 2009 Mar 11. PMID:19279319 doi:http://dx.doi.org/10.1212/01.wnl.0000346517.98982.1b
- ↑ Meeus B, Nuytemans K, Crosiers D, Engelborghs S, Pals P, Pickut B, Peeters K, Mattheijssens M, Corsmit E, Cras P, De Deyn PP, Theuns J, Van Broeckhoven C. GIGYF2 has no major role in Parkinson genetic etiology in a Belgian population. Neurobiol Aging. 2011 Feb;32(2):308-12. doi:, 10.1016/j.neurobiolaging.2009.02.016. Epub 2009 Mar 24. PMID:19321232 doi:http://dx.doi.org/10.1016/j.neurobiolaging.2009.02.016
- ↑ Guo Y, Jankovic J, Zhu S, Le W, Song Z, Xie W, Liao D, Yang H, Deng H. GIGYF2 Asn56Ser and Asn457Thr mutations in Parkinson disease patients. Neurosci Lett. 2009 May 1;454(3):209-11. doi: 10.1016/j.neulet.2009.03.039. Epub , 2009 Mar 16. PMID:19429085 doi:http://dx.doi.org/10.1016/j.neulet.2009.03.039
- ↑ Di Fonzo A, Fabrizio E, Thomas A, Fincati E, Marconi R, Tinazzi M, Breedveld GJ, Simons EJ, Chien HF, Ferreira JJ, Horstink MW, Abbruzzese G, Borroni B, Cossu G, Dalla Libera A, Fabbrini G, Guidi M, De Mari M, Lopiano L, Martignoni E, Marini P, Onofrj M, Padovani A, Stocchi F, Toni V, Sampaio C, Barbosa ER, Meco G, Oostra BA, Bonifati V. GIGYF2 mutations are not a frequent cause of familial Parkinson's disease. Parkinsonism Relat Disord. 2009 Nov;15(9):703-5. doi:, 10.1016/j.parkreldis.2009.05.001. Epub 2009 May 31. PMID:19482505 doi:http://dx.doi.org/10.1016/j.parkreldis.2009.05.001
- ↑ Zhang Y, Zheng L, Zhang T, Wang Y, Xiao Q, Fei QZ, Cui PJ, Cao L, Chen SD. GIGYF2 Asn56Ser mutation is rare in Chinese Parkinson's disease patients. Neurosci Lett. 2009 Oct 9;463(3):172-5. doi: 10.1016/j.neulet.2009.07.067. Epub, 2009 Jul 26. PMID:19638301 doi:http://dx.doi.org/10.1016/j.neulet.2009.07.067
- ↑ Lesage S, Condroyer C, Lohman E, Troiano A, Tison F, Viallet F, Damier P, Tranchant C, Vidhaillet M, Ouvrard-Hernandez AM, Durr A, Brice A. Follow-up study of the GIGYF2 gene in French families with Parkinson's disease. Neurobiol Aging. 2010 Jun;31(6):1069-71; discussion 1072-4. doi:, 10.1016/j.neurobiolaging.2009.06.008. Epub 2009 Dec 8. PMID:20004041 doi:http://dx.doi.org/10.1016/j.neurobiolaging.2009.06.008
- ↑ Guella I, Pistocchi A, Asselta R, Rimoldi V, Ghilardi A, Sironi F, Trotta L, Primignani P, Zini M, Zecchinelli A, Coviello D, Pezzoli G, Del Giacco L, Duga S, Goldwurm S. Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene. Neurobiol Aging. 2011 Nov;32(11):1994-2005. doi:, 10.1016/j.neurobiolaging.2009.12.016. Epub 2010 Jan 8. PMID:20060621 doi:http://dx.doi.org/10.1016/j.neurobiolaging.2009.12.016
- ↑ Giovannone B, Lee E, Laviola L, Giorgino F, Cleveland KA, Smith RJ. Two novel proteins that are linked to insulin-like growth factor (IGF-I) receptors by the Grb10 adapter and modulate IGF-I signaling. J Biol Chem. 2003 Aug 22;278(34):31564-73. Epub 2003 May 27. PMID:12771153 doi:http://dx.doi.org/10.1074/jbc.M211572200
- ↑ Morita M, Ler LW, Fabian MR, Siddiqui N, Mullin M, Henderson VC, Alain T, Fonseca BD, Karashchuk G, Bennett CF, Kabuta T, Higashi S, Larsson O, Topisirovic I, Smith RJ, Gingras AC, Sonenberg N. A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol Cell Biol. 2012 Sep;32(17):3585-93. doi: 10.1128/MCB.00455-12. Epub 2012 Jul , 2. PMID:22751931 doi:http://dx.doi.org/10.1128/MCB.00455-12
- ↑ Sobti M, Mead BJ, Stewart AG, Igreja C, Christie M. Molecular basis for GIGYF-TNRC6 complex assembly. RNA. 2023 Feb 28:rna.079596.123. PMID:36854607 doi:10.1261/rna.079596.123
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