1wf0

From Proteopedia

(Difference between revisions)

Revision as of 06:52, 2 March 2022

Solution structure of RRM domain in TAR DNA-binding protein-43

Structural highlights

1wf0 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	HEP00195 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Disease

[TADBP_HUMAN] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:612069]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13]

Function

[TADBP_HUMAN] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.^[14] ^[15]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rub U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010 Aug 26;466(7310):1069-75. doi: 10.1038/nature09320. PMID:20740007 doi:10.1038/nature09320
↑ Gitcho MA, Baloh RH, Chakraverty S, Mayo K, Norton JB, Levitch D, Hatanpaa KJ, White CL 3rd, Bigio EH, Caselli R, Baker M, Al-Lozi MT, Morris JC, Pestronk A, Rademakers R, Goate AM, Cairns NJ. TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol. 2008 Apr;63(4):535-8. doi: 10.1002/ana.21344. PMID:18288693 doi:10.1002/ana.21344
↑ Yokoseki A, Shiga A, Tan CF, Tagawa A, Kaneko H, Koyama A, Eguchi H, Tsujino A, Ikeuchi T, Kakita A, Okamoto K, Nishizawa M, Takahashi H, Onodera O. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol. 2008 Apr;63(4):538-42. doi: 10.1002/ana.21392. PMID:18438952 doi:10.1002/ana.21392
↑ Van Deerlin VM, Leverenz JB, Bekris LM, Bird TD, Yuan W, Elman LB, Clay D, Wood EM, Chen-Plotkin AS, Martinez-Lage M, Steinbart E, McCluskey L, Grossman M, Neumann M, Wu IL, Yang WS, Kalb R, Galasko DR, Montine TJ, Trojanowski JQ, Lee VM, Schellenberg GD, Yu CE. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 2008 May;7(5):409-16. doi: 10.1016/S1474-4422(08)70071-1. Epub, 2008 Apr 7. PMID:18396105 doi:10.1016/S1474-4422(08)70071-1
↑ Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet. 2008 May;40(5):572-4. doi: 10.1038/ng.132. Epub 2008 Mar 30. PMID:18372902 doi:10.1038/ng.132
↑ Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008 Mar 21;319(5870):1668-72. doi: 10.1126/science.1154584. Epub 2008, Feb 28. PMID:18309045 doi:10.1126/science.1154584
↑ Benajiba L, Le Ber I, Camuzat A, Lacoste M, Thomas-Anterion C, Couratier P, Legallic S, Salachas F, Hannequin D, Decousus M, Lacomblez L, Guedj E, Golfier V, Camu W, Dubois B, Campion D, Meininger V, Brice A. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol. 2009 Apr;65(4):470-3. doi: 10.1002/ana.21612. PMID:19350673 doi:10.1002/ana.21612
↑ Corrado L, Ratti A, Gellera C, Buratti E, Castellotti B, Carlomagno Y, Ticozzi N, Mazzini L, Testa L, Taroni F, Baralle FE, Silani V, D'Alfonso S. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum Mutat. 2009 Apr;30(4):688-94. doi: 10.1002/humu.20950. PMID:19224587 doi:10.1002/humu.20950
↑ Borroni B, Bonvicini C, Alberici A, Buratti E, Agosti C, Archetti S, Papetti A, Stuani C, Di Luca M, Gennarelli M, Padovani A. Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum Mutat. 2009 Nov;30(11):E974-83. doi: 10.1002/humu.21100. PMID:19655382 doi:10.1002/humu.21100
↑ Luquin N, Yu B, Saunderson RB, Trent RJ, Pamphlett R. Genetic variants in the promoter of TARDBP in sporadic amyotrophic lateral sclerosis. Neuromuscul Disord. 2009 Oct;19(10):696-700. doi: 10.1016/j.nmd.2009.07.005. Epub, 2009 Aug 19. PMID:19695877 doi:10.1016/j.nmd.2009.07.005
↑ Chio A, Borghero G, Pugliatti M, Ticca A, Calvo A, Moglia C, Mutani R, Brunetti M, Ossola I, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Cossu P, Abramzon Y, Johnson JO, Nalls MA, Arepalli S, Chong S, Hernandez DG, Traynor BJ, Restagno G. Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Arch Neurol. 2011 May;68(5):594-8. doi: 10.1001/archneurol.2010.352. Epub 2011, Jan 10. PMID:21220647 doi:10.1001/archneurol.2010.352
↑ Orru S, Manolakos E, Orru N, Kokotas H, Mascia V, Carcassi C, Petersen MB. High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis. Clin Genet. 2012 Feb;81(2):172-8. doi: 10.1111/j.1399-0004.2011.01668.x. Epub, 2011 Apr 18. PMID:21418058 doi:10.1111/j.1399-0004.2011.01668.x
↑ Chiang HH, Andersen PM, Tysnes OB, Gredal O, Christensen PB, Graff C. Novel TARDBP mutations in Nordic ALS patients. J Hum Genet. 2012 May;57(5):316-9. doi: 10.1038/jhg.2012.24. Epub 2012 Mar 29. PMID:22456481 doi:10.1038/jhg.2012.24
↑ Strong MJ, Volkening K, Hammond R, Yang W, Strong W, Leystra-Lantz C, Shoesmith C. TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci. 2007 Jun;35(2):320-7. Epub 2007 Mar 20. PMID:17481916 doi:10.1016/j.mcn.2007.03.007
↑ Buratti E, Dork T, Zuccato E, Pagani F, Romano M, Baralle FE. Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J. 2001 Apr 2;20(7):1774-84. PMID:11285240 doi:10.1093/emboj/20.7.1774

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wf0"

@@ Line 3: / Line 3: @@
 <StructureSection load='1wf0' size='340' side='right'caption='[[1wf0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1wf0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WF0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1WF0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1wf0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WF0 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HEP00195 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HEP00195 ([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'>[http://proteopedia.org/fgij/fg.htm?mol=1wf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wf0 OCA], [http://pdbe.org/1wf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wf0 RCSB], [http://www.ebi.ac.uk/pdbsum/1wf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wf0 ProSAT], [http://www.topsan.org/Proteins/RSGI/1wf0 TOPSAN]</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=1wf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wf0 OCA], [https://pdbe.org/1wf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wf0 RCSB], [https://www.ebi.ac.uk/pdbsum/1wf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wf0 ProSAT], [https://www.topsan.org/Proteins/RSGI/1wf0 TOPSAN]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[http://omim.org/entry/612069 612069]]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>
+[[https://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[https://omim.org/entry/612069 612069]]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>
+[[https://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 21: / Line 21: @@
 </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wf0 ConSurf].
 <div style="clear:both"></div>
-==See Also==
-*[[Tdp-43|Tdp-43]]
 == References ==
 <references/>

1wf0

From Proteopedia

Revision as of 06:52, 2 March 2022

Solution structure of RRM domain in TAR DNA-binding protein-43

Structural highlights

Disease

Function

Evolutionary Conservation

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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