2l4z

From Proteopedia

(Difference between revisions)

Revision as of 08:33, 1 January 2020

NMR structure of fusion of CtIP (641-685) to LMO4-LIM1 (18-82)

Structural highlights

2l4z 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.
Ligands:
Related:	1m3v, 1rut
Gene:	LMO4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CTIP_HUMAN] Seckel syndrome;Jawad syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk (PubMed:21799032). Associated with sensitivity to tamoxifen in certain breast cancer cell lines (PubMed:18171986).^[1] ^[2]

Function

[CTIP_HUMAN] Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:10764811, PubMed:10910365, PubMed:15485915, PubMed:16581787, PubMed:16818604, PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:20829486). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).[UniProtKB:Q80YR6]^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

Publication Abstract from PubMed

LIM-only protein 4 (LMO4) is strongly linked to the progression of breast cancer. Although the mechanisms underlying this phenomenon are not well understood, a role is emerging for LMO4 in regulation of the cell cycle. We determined the solution structure of LMO4 in complex with CtIP (C-terminal binding protein interacting protein)/RBBP8, a tumour suppressor protein that is involved in cell cycle progression, DNA repair and transcriptional regulation. Our data reveal that CtIP and the essential LMO cofactor LDB1 (LIM-domain binding protein 1) bind to the same face on LMO4 and cannot simultaneously bind to LMO4. We hypothesise that overexpression of LMO4 may disrupt some of the normal tumour suppressor activities of CtIP, thereby contributing to breast cancer progression.

Structural Basis of the Interaction of the Breast Cancer Oncogene LMO4 with the Tumour Suppressor CtIP/RBBP8.,Stokes PH, Liew CW, Kwan AH, Foo P, Barker HE, Djamirze A, O'Reilly V, Visvader JE, Mackay JP, Matthews JM J Mol Biol. 2013 Apr 12;425(7):1101-10. doi: 10.1016/j.jmb.2013.01.017. Epub 2013, Jan 23. PMID:23353824^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu M, Soler DR, Abba MC, Nunez MI, Baer R, Hatzis C, Llombart-Cussac A, Llombart-Bosch A, Aldaz CM. CtIP silencing as a novel mechanism of tamoxifen resistance in breast cancer. Mol Cancer Res. 2007 Dec;5(12):1285-95. doi: 10.1158/1541-7786.MCR-07-0126. PMID:18171986 doi:http://dx.doi.org/10.1158/1541-7786.MCR-07-0126
↑ Rebbeck TR, Mitra N, Domchek SM, Wan F, Friebel TM, Tran TV, Singer CF, Tea MK, Blum JL, Tung N, Olopade OI, Weitzel JN, Lynch HT, Snyder CL, Garber JE, Antoniou AC, Peock S, Evans DG, Paterson J, Kennedy MJ, Donaldson A, Dorkins H, Easton DF, Rubinstein WS, Daly MB, Isaacs C, Nevanlinna H, Couch FJ, Andrulis IL, Freidman E, Laitman Y, Ganz PA, Tomlinson GE, Neuhausen SL, Narod SA, Phelan CM, Greenberg R, Nathanson KL. Modification of BRCA1-Associated Breast and Ovarian Cancer Risk by BRCA1-Interacting Genes. Cancer Res. 2011 Sep 1;71(17):5792-805. doi: 10.1158/0008-5472.CAN-11-0773. Epub , 2011 Jul 28. PMID:21799032 doi:http://dx.doi.org/10.1158/0008-5472.CAN-11-0773
↑ Yu X, Baer R. Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor. J Biol Chem. 2000 Jun 16;275(24):18541-9. PMID:10764811 doi:10.1074/jbc.M909494199
↑ Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH. Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature. 2000 Jul 13;406(6792):210-5. PMID:10910365 doi:10.1038/35018134
↑ Yu X, Chen J. DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol Cell Biol. 2004 Nov;24(21):9478-86. PMID:15485915 doi:10.1128/MCB.24.21.9478-9486.2004
↑ Liu F, Lee WH. CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway during G1/S progression. Mol Cell Biol. 2006 Apr;26(8):3124-34. PMID:16581787 doi:10.1128/MCB.26.8.3124-3134.2006
↑ Yu X, Fu S, Lai M, Baer R, Chen J. BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP. Genes Dev. 2006 Jul 1;20(13):1721-6. PMID:16818604 doi:10.1101/gad.1431006
↑ Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP. Human CtIP promotes DNA end resection. Nature. 2007 Nov 22;450(7169):509-14. Epub 2007 Oct 28. PMID:17965729 doi:10.1038/nature06337
↑ Huertas P, Jackson SP. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J Biol Chem. 2009 Apr 3;284(14):9558-65. doi: 10.1074/jbc.M808906200. Epub 2009, Feb 7. PMID:19202191 doi:10.1074/jbc.M808906200
↑ Yuan J, Chen J. N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair. J Biol Chem. 2009 Nov 13;284(46):31746-52. doi: 10.1074/jbc.M109.023424. Epub, 2009 Sep 16. PMID:19759395 doi:10.1074/jbc.M109.023424
↑ You Z, Shi LZ, Zhu Q, Wu P, Zhang YW, Basilio A, Tonnu N, Verma IM, Berns MW, Hunter T. CtIP links DNA double-strand break sensing to resection. Mol Cell. 2009 Dec 25;36(6):954-69. doi: 10.1016/j.molcel.2009.12.002. PMID:20064462 doi:10.1016/j.molcel.2009.12.002
↑ Kaidi A, Weinert BT, Choudhary C, Jackson SP. Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science. 2010 Sep 10;329(5997):1348-53. doi: 10.1126/science.1192049. PMID:20829486 doi:10.1126/science.1192049
↑ Stokes PH, Liew CW, Kwan AH, Foo P, Barker HE, Djamirze A, O'Reilly V, Visvader JE, Mackay JP, Matthews JM. Structural Basis of the Interaction of the Breast Cancer Oncogene LMO4 with the Tumour Suppressor CtIP/RBBP8. J Mol Biol. 2013 Apr 12;425(7):1101-10. doi: 10.1016/j.jmb.2013.01.017. Epub 2013, Jan 23. PMID:23353824 doi:http://dx.doi.org/10.1016/j.jmb.2013.01.017

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l4z"

@@ Line 1: / Line 1: @@
 ==NMR structure of fusion of CtIP (641-685) to LMO4-LIM1 (18-82)==
-<StructureSection load='2l4z' size='340' side='right' caption='[[2l4z]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2l4z' size='340' side='right'caption='[[2l4z]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2l4z]] 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=2L4Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L4Z FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1m3v|1m3v]], [[1rut|1rut]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTIP, LMO4, RBBP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LMO4 ([http://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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l4z OCA], [http://pdbe.org/2l4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l4z RCSB], [http://www.ebi.ac.uk/pdbsum/2l4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l4z ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/COM1_HUMAN COM1_HUMAN]] Seckel syndrome. Defects in RBBP8 are a cause of Seckel syndrome type 2 (SCKL2) [MIM:[http://omim.org/entry/606744 606744]]. SCKL2 is a rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.<ref>PMID:21998596</ref>   Defects in RBBP8 are a cause of Jawad disease (JWDS) [MIM:[http://omim.org/entry/251255 251255]]. JWDS is a syndrome characterized by congenital microcephaly, moderately severe mental retardation, and symmetrical digital anomalies. Digital malformations of variable degree inclued hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly.<ref>PMID:21998596</ref>   Note=Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk. Exhibits sensitivity to tamoxifen in certain breast cancer cell lines.
+[[http://www.uniprot.org/uniprot/CTIP_HUMAN CTIP_HUMAN]] Seckel syndrome;Jawad syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  Genetic variability in RBBP8 is noted as a factor in BRCA1-associated breast cancer risk (PubMed:21799032). Associated with sensitivity to tamoxifen in certain breast cancer cell lines (PubMed:18171986).<ref>PMID:18171986</ref> <ref>PMID:21799032</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/COM1_HUMAN COM1_HUMAN]] Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in processing meiotic and mitotic double-strand breaks (DSBs) by ensuring both resection and intrachromosomal association of the broken ends. Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage. Promotes microhomology-mediated alternative end joining (A-NHEJ) during class-switch recombination and plays an essential role in chromosomal translocations.<ref>PMID:10764811</ref> <ref>PMID:10910365</ref> <ref>PMID:15485915</ref> <ref>PMID:16818604</ref> <ref>PMID:16581787</ref> <ref>PMID:17965729</ref> <ref>PMID:19202191</ref> <ref>PMID:19759395</ref> <ref>PMID:20064462</ref> <ref>PMID:20829486</ref>
+[[http://www.uniprot.org/uniprot/CTIP_HUMAN CTIP_HUMAN]] Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:10764811, PubMed:10910365, PubMed:15485915, PubMed:16581787, PubMed:16818604, PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:20829486). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).[UniProtKB:Q80YR6]<ref>PMID:10764811</ref> <ref>PMID:10910365</ref> <ref>PMID:15485915</ref> <ref>PMID:16581787</ref> <ref>PMID:16818604</ref> <ref>PMID:17965729</ref> <ref>PMID:19202191</ref> <ref>PMID:19759395</ref> <ref>PMID:20064462</ref> <ref>PMID:20829486</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Kwan, A H]]
 [[Category: Liew, C]]

2l4z

From Proteopedia

Revision as of 08:33, 1 January 2020

NMR structure of fusion of CtIP (641-685) to LMO4-LIM1 (18-82)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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