| Structural highlights
Function
[EST1A_HUMAN] Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the ability of TERT to elongate telomeres. Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization. Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER).[1] [2] [3] [4] [5] Plays a role in nonsense-mediated mRNA decay. Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA.[6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Saccharomyces cerevisiae Est1p is a telomerase-associated protein essential for telomere length homeostasis. hEST1A is one of the three human Est1p homologues and is considered to be involved not only in regulation of telomere elongation or capping but also in nonsense-mediated degradation of RNA. hEST1A is composed of two conserved regions, Est1p homology and PIN (PilT N-terminus) domains. The present study shows the crystal structure of the PIN domain at 1.8 A resolution. The overall structure is composed of an alpha/beta fold or a core structure similar to the counterpart of 5' nucleases and an extended structure absent from archaeal PIN-domain proteins and 5' nucleases. The structural properties of the PIN domain indicate its putative active center consisting of invariant acidic amino acid residues, which is geometrically similar to the active center of 5' nucleases and an archaeal PAE2754 PIN-domain protein associated with exonuclease activity.
Crystal structure of the PIN domain of human telomerase-associated protein EST1A.,Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M Proteins. 2007 Sep 1;68(4):980-9. PMID:17557331[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol. 2003 Apr 1;13(7):568-74. PMID:12676087
- ↑ Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L. Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003 Apr 15;13(8):698-704. PMID:12699629
- ↑ Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008 Dec;14(12):2609-17. doi: 10.1261/rna.1386208. Epub 2008 Oct 30. PMID:18974281 doi:http://dx.doi.org/10.1261/rna.1386208
- ↑ Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009 Jan;16(1):49-55. doi: 10.1038/nsmb.1530. Epub 2008 Dec , 7. PMID:19060897 doi:http://dx.doi.org/10.1038/nsmb.1530
- ↑ Glavan F, Behm-Ansmant I, Izaurralde E, Conti E. Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. PMID:17053788
- ↑ Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol. 2003 Apr 1;13(7):568-74. PMID:12676087
- ↑ Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L. Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003 Apr 15;13(8):698-704. PMID:12699629
- ↑ Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008 Dec;14(12):2609-17. doi: 10.1261/rna.1386208. Epub 2008 Oct 30. PMID:18974281 doi:http://dx.doi.org/10.1261/rna.1386208
- ↑ Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009 Jan;16(1):49-55. doi: 10.1038/nsmb.1530. Epub 2008 Dec , 7. PMID:19060897 doi:http://dx.doi.org/10.1038/nsmb.1530
- ↑ Glavan F, Behm-Ansmant I, Izaurralde E, Conti E. Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. PMID:17053788
- ↑ Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M. Crystal structure of the PIN domain of human telomerase-associated protein EST1A. Proteins. 2007 Sep 1;68(4):980-9. PMID:17557331 doi:10.1002/prot.21351
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