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| | <StructureSection load='3bu8' size='340' side='right'caption='[[3bu8]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='3bu8' size='340' side='right'caption='[[3bu8]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3bu8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BU8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3bu8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BU8 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bua|3bua]], [[3bqo|3bqo]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TERF2, TRBF2, TRF2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TINF2, TIN2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bu8 OCA], [https://pdbe.org/3bu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bu8 RCSB], [https://www.ebi.ac.uk/pdbsum/3bu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bu8 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bu8 OCA], [https://pdbe.org/3bu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bu8 RCSB], [https://www.ebi.ac.uk/pdbsum/3bu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bu8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[https://www.uniprot.org/uniprot/TINF2_HUMAN TINF2_HUMAN]] Defects in TINF2 are a cause of dyskeratosis congenita autosomal dominant type 3 (DKCA3) [MIM:[https://omim.org/entry/613990 613990]]. A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.<ref>PMID:18252230</ref> Defects in TINF2 are a cause of retinopathy exudative with bone marrow failure (ERBMF) [MIM:[https://omim.org/entry/268130 268130]]; also known as Revesz syndrome. ERBMF is characterized by bilateral exudative retinopathy, bone marrow hypoplasia, nail dystrophy, fine hair, cerebellar hypoplasia, and growth retardation.<ref>PMID:18252230</ref> | |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TERF2_HUMAN TERF2_HUMAN]] Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.<ref>PMID:9476899</ref> <ref>PMID:16166375</ref> <ref>PMID:20655466</ref> [[https://www.uniprot.org/uniprot/TINF2_HUMAN TINF2_HUMAN]] Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Plays a role in shelterin complex assembly. Isoform 1 may have additional role in tethering telomeres to the nuclear matrix.<ref>PMID:16166375</ref> <ref>PMID:16880378</ref> <ref>PMID:19229133</ref>
| + | [https://www.uniprot.org/uniprot/TERF2_HUMAN TERF2_HUMAN] Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.<ref>PMID:9476899</ref> <ref>PMID:16166375</ref> <ref>PMID:20655466</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baciu, P]] | + | [[Category: Baciu P]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Donigian, J R]] | + | [[Category: Donigian JR]] |
| - | [[Category: Lange, T de]]
| + | [[Category: Lei M]] |
| - | [[Category: Lei, M]] | + | [[Category: Yang Y]] |
| - | [[Category: Overbeek, M van]]
| + | [[Category: De Lange T]] |
| - | [[Category: Yang, Y]] | + | [[Category: Van Overbeek M]] |
| - | [[Category: Alternative splicing]] | + | |
| - | [[Category: Cell cycle]] | + | |
| - | [[Category: Chromosomal protein]]
| + | |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Telomere]]
| + | |
| - | [[Category: Trf2 trfh domain trf2 dimerization domain tin2 peptide]]
| + | |
| Structural highlights
Function
TERF2_HUMAN Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.[1] [2] [3]
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
Mammalian telomeres are protected by a six-protein complex, shelterin. Shelterin contains two closely related proteins, TRF1 and TRF2, which recruit various proteins to telomeres. Here we dissect the interactions of TRF1 and TRF2 with their shared binding partner, TIN2, and other shelterin accessory factors. TRF1 recognizes TIN2 using a conserved molecular surface in its TRF homology (TRFH) domain. However, this same surface does not act as a TIN2 binding site in TRF2, and TIN2 binding to TRF2 is mediated by a region outside the TRFH domain. Instead, the TRFH docking site of TRF2 binds a shelterin accessory factor Apollo, which does not interact with the TRFH domain of TRF1. Conversely, the TRFH domain of TRF1, but not of TRF2, interacts with another shelterin associated factor PinX1.
A Shared Docking Motif in TRF1 and TRF2 Used for Differential Recruitment of Telomeric Proteins.,Chen Y, Yang Y, van Overbeek M, Donigian JR, Baciu P, de Lange T, Lei M Science. 2008 Jan 17;. PMID:18202258[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998 Feb 6;92(3):401-13. PMID:9476899
- ↑ de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005 Sep 15;19(18):2100-10. PMID:16166375 doi:10.1101/gad.1346005
- ↑ Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Leger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S, Verhoeyen E, Britton S, Calsou P, Salles B, Bizard A, Nadal M, Salvati E, Sabatier L, Wu Y, Biroccio A, Londono-Vallejo A, Giraud-Panis MJ, Gilson E. TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell. 2010 Jul 23;142(2):230-42. doi: 10.1016/j.cell.2010.05.032. PMID:20655466 doi:10.1016/j.cell.2010.05.032
- ↑ Chen Y, Yang Y, van Overbeek M, Donigian JR, Baciu P, de Lange T, Lei M. A Shared Docking Motif in TRF1 and TRF2 Used for Differential Recruitment of Telomeric Proteins. Science. 2008 Jan 17;. PMID:18202258
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