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| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3ddp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDP FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3ddp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDP FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RC8:(2R)-2-({9-(1-METHYLETHYL)-6-[(4-PYRIDIN-2-YLBENZYL)AMINO]-9H-PURIN-2-YL}AMINO)BUTAN-1-OL'>RC8</scene></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]] 2.7Å</td></tr> |
| <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>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RC8:(2R)-2-({9-(1-METHYLETHYL)-6-[(4-PYRIDIN-2-YLBENZYL)AMINO]-9H-PURIN-2-YL}AMINO)BUTAN-1-OL'>RC8</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ddq|3ddq]]</div></td></tr>
| |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDK2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CCNA2, CCNA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>
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| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </span></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=3ddp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ddp OCA], [https://pdbe.org/3ddp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ddp RCSB], [https://www.ebi.ac.uk/pdbsum/3ddp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ddp 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=3ddp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ddp OCA], [https://pdbe.org/3ddp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ddp RCSB], [https://www.ebi.ac.uk/pdbsum/3ddp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ddp ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function ==
| |
| [[https://www.uniprot.org/uniprot/CDK2_HUMAN CDK2_HUMAN]] Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.<ref>PMID:10499802</ref> <ref>PMID:11051553</ref> <ref>PMID:10995386</ref> <ref>PMID:10995387</ref> <ref>PMID:10884347</ref> <ref>PMID:11113184</ref> <ref>PMID:15800615</ref> <ref>PMID:18372919</ref> <ref>PMID:20147522</ref> <ref>PMID:20079829</ref> <ref>PMID:20935635</ref> <ref>PMID:20195506</ref> <ref>PMID:19966300</ref> <ref>PMID:21262353</ref> <ref>PMID:21596315</ref> <ref>PMID:21319273</ref> <ref>PMID:17495531</ref> [[https://www.uniprot.org/uniprot/CCNA2_BOVIN CCNA2_BOVIN]] Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.
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| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| <jmolCheckbox> | | <jmolCheckbox> |
| <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dd/3ddp_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dd/3ddp_consurf.spt"</scriptWhenChecked> |
| <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <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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| </StructureSection> | | </StructureSection> |
| [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| [[Category: Cyclin-dependent kinase]]
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| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Echalier, A]] | | [[Category: Echalier A]] |
| [[Category: Endicott, J A]] | | [[Category: Endicott JA]] |
| [[Category: Atp-binding]]
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| [[Category: Cell cycle]]
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| [[Category: Cell division]]
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| [[Category: Cyclin]]
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| [[Category: Cytoplasm]]
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| [[Category: Mitosis]]
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| [[Category: Nucleotide-binding]]
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| [[Category: Nucleus]]
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| [[Category: Phosphoprotein]]
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| [[Category: Phosphorylation]]
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| [[Category: Polymorphism]]
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| [[Category: Ser/thr protein kinase]]
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| [[Category: Serine/threonine-protein kinase]]
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| [[Category: Transferase-cell cycle complex]]
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