2ast

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==Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide==
==Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide==
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<StructureSection load='2ast' size='340' side='right' caption='[[2ast]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='2ast' size='340' side='right'caption='[[2ast]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2ast]] is a 4 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=2AST OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AST FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2ast]] 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=2AST OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AST FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ass|2ass]], [[1fqv|1fqv]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ast FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ast OCA], [https://pdbe.org/2ast PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ast RCSB], [https://www.ebi.ac.uk/pdbsum/2ast PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ast ProSAT]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SKP1A, EMC19, OCP2, SKP1, TCEB1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SKP2, FBXL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CKS1, CKS1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=2ast FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ast OCA], [http://pdbe.org/2ast PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ast RCSB], [http://www.ebi.ac.uk/pdbsum/2ast PDBsum]</span></td></tr>
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</table>
</table>
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== Disease ==
 
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[[http://www.uniprot.org/uniprot/CDN1B_HUMAN CDN1B_HUMAN]] Defects in CDKN1B are the cause of multiple endocrine neoplasia type 4 (MEN4) [MIM:[http://omim.org/entry/610755 610755]]. Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.<ref>PMID:17030811</ref>
 
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/CDN1B_HUMAN CDN1B_HUMAN]] Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.<ref>PMID:10831586</ref> <ref>PMID:12244301</ref> <ref>PMID:16782892</ref> <ref>PMID:19075005</ref> <ref>PMID:17254966</ref> [[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref> [[http://www.uniprot.org/uniprot/CKS1_HUMAN CKS1_HUMAN]] Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. [[http://www.uniprot.org/uniprot/SKP2_HUMAN SKP2_HUMAN]] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.<ref>PMID:12435635</ref> <ref>PMID:11931757</ref> <ref>PMID:12840033</ref> <ref>PMID:12769844</ref> <ref>PMID:15342634</ref> <ref>PMID:16262255</ref> <ref>PMID:15949444</ref> <ref>PMID:16103164</ref> <ref>PMID:15668399</ref> <ref>PMID:16951159</ref> <ref>PMID:16581786</ref> <ref>PMID:17908926</ref> <ref>PMID:17962192</ref> <ref>PMID:22770219</ref>
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[https://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/as/2ast_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/as/2ast_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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</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=2ast ConSurf].
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<div style="clear:both"></div>
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<div class="pdbe-citations 2ast" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 2ast" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Cyclin-dependent kinase regulatory subunit 3D structures|Cyclin-dependent kinase regulatory subunit 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Hao, B]]
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[[Category: Large Structures]]
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[[Category: Pagano, M]]
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[[Category: Hao B]]
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[[Category: Pavletich, N P]]
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[[Category: Pagano M]]
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[[Category: Schulman, B A]]
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[[Category: Pavletich NP]]
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[[Category: Wu, G]]
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[[Category: Schulman BA]]
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[[Category: Zhang, N]]
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[[Category: Wu G]]
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[[Category: Cell cycle]]
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[[Category: Zhang N]]
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[[Category: Ligase-ligase inhibitor complex]]
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[[Category: Lrr]]
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[[Category: Protein turnover complex]]
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[[Category: Scf-substrate complex]]
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Current revision

Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide

PDB ID 2ast

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