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5yco

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Revision as of 07:58, 6 December 2017

Complex structure of PCNA with UHRF2

Structural highlights

5yco is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PCNA (HUMAN)
Activity:	RING-type E3 ubiquitin transferase, with EC number 2.3.2.27
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[UHRF2_HUMAN] Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.

Function

[PCNA_HUMAN] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.^[1] ^[2] [UHRF2_HUMAN] E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131.^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

UHRF2 (Ubiquitin-like with PHD and ring finger domains 2) is an E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications and cell cycle regulation by interacting with multiple epigenetic or cell-cycle related proteins. Previous studied have identified PCNA (Proliferating cell nuclear antigen) as an interacting partner of UHRF2 by using the antibody microarray. However, the molecular mechanism and the function of UHRF2-PCNA interaction remains unclear. Here, we report the complex structure of PCNA and the peptide (784NEILQTLLDLFFPGYSK800) derived from UHRF2 that contains a PIP box. Structural analysis combined with mutagenesis experiments provide the molecular basis for the recognition of UHRF2 by PCNA via PIP-box.

Structure insights into the molecular mechanism of the interaction between UHRF2 and PCNA.,Chen W, Wu M, Hang T, Wang C, Zhang X, Zang J Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):575-580. doi:, 10.1016/j.bbrc.2017.09.102. Epub 2017 Sep 23. PMID:28951215^[9]

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

References

↑ Burkovics P, Hajdu I, Szukacsov V, Unk I, Haracska L. Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage. Nucleic Acids Res. 2009 Jul;37(13):4247-55. doi: 10.1093/nar/gkp357. Epub 2009, May 13. PMID:19443450 doi:10.1093/nar/gkp357
↑ Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105
↑ Mori T, Li Y, Hata H, Ono K, Kochi H. NIRF, a novel RING finger protein, is involved in cell-cycle regulation. Biochem Biophys Res Commun. 2002 Aug 23;296(3):530-6. PMID:12176013
↑ Li Y, Mori T, Hata H, Homma Y, Kochi H. NIRF induces G1 arrest and associates with Cdk2. Biochem Biophys Res Commun. 2004 Jun 25;319(2):464-8. PMID:15178429 doi:http://dx.doi.org/10.1016/j.bbrc.2004.04.190
↑ Mori T, Li Y, Hata H, Kochi H. NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-containing nuclear protein. FEBS Lett. 2004 Jan 16;557(1-3):209-14. PMID:14741369
↑ Unoki M, Nishidate T, Nakamura Y. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 2004 Oct 7;23(46):7601-10. PMID:15361834 doi:10.1038/sj.onc.1208053
↑ Mori T, Ikeda DD, Fukushima T, Takenoshita S, Kochi H. NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor. Cell Cycle. 2011 Oct 1;10(19):3284-99. doi: 10.4161/cc.10.19.17176. Epub 2011 Oct, 1. PMID:21952639 doi:http://dx.doi.org/10.4161/cc.10.19.17176
↑ Oh Y, Chung KC. UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131. J Biol Chem. 2013 Mar 29;288(13):9102-11. doi: 10.1074/jbc.M112.438234. Epub 2013, Feb 12. PMID:23404503 doi:http://dx.doi.org/10.1074/jbc.M112.438234
↑ Chen W, Wu M, Hang T, Wang C, Zhang X, Zang J. Structure insights into the molecular mechanism of the interaction between UHRF2 and PCNA. Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):575-580. doi:, 10.1016/j.bbrc.2017.09.102. Epub 2017 Sep 23. PMID:28951215 doi:http://dx.doi.org/10.1016/j.bbrc.2017.09.102

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/5yco"

@@ Line 3: / Line 3: @@
 <StructureSection load='5yco' size='340' side='right' caption='[[5yco]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5yco]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YCO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5yco]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YCO FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PCNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></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=5yco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yco OCA], [http://pdbe.org/5yco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yco RCSB], [http://www.ebi.ac.uk/pdbsum/5yco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yco ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: RING-type E3 ubiquitin transferase]]
 [[Category: Chen, W]]

5yco

From Proteopedia

Revision as of 07:58, 6 December 2017

Complex structure of PCNA with UHRF2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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