2w1h: Difference between revisions
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<StructureSection load='2w1h' size='340' side='right'caption='[[2w1h]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='2w1h' size='340' side='right'caption='[[2w1h]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2w1h]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2w1h]] is a 1 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=2W1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W1H FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L0F:N-[3-(1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL]BENZAMIDE'>L0F</scene></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=2w1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w1h OCA], [https://pdbe.org/2w1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w1h RCSB], [https://www.ebi.ac.uk/pdbsum/2w1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w1h ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Berdini V]] | |||
[[Category: Berdini | [[Category: Boulstridge JA]] | ||
[[Category: Boulstridge | [[Category: Carr MG]] | ||
[[Category: Cross DM]] | |||
[[Category: Carr | [[Category: Curry J]] | ||
[[Category: Cross | [[Category: Devine LA]] | ||
[[Category: Curry | [[Category: Early TR]] | ||
[[Category: Devine | [[Category: Fazal L]] | ||
[[Category: Early | [[Category: Gill AL]] | ||
[[Category: Fazal | [[Category: Heathcote M]] | ||
[[Category: Gill | [[Category: Howard S]] | ||
[[Category: Heathcote | [[Category: Maman S]] | ||
[[Category: Howard | [[Category: Matthews JE]] | ||
[[Category: Maman | [[Category: McMenamin RL]] | ||
[[Category: Matthews | [[Category: Navarro EF]] | ||
[[Category: McMenamin | [[Category: O'Brien MA]] | ||
[[Category: Navarro | [[Category: O'Reilly M]] | ||
[[Category: | [[Category: Rees DC]] | ||
[[Category: Reilly | [[Category: Reule M]] | ||
[[Category: Reule | [[Category: Tisi D]] | ||
[[Category: Tisi | [[Category: Vinkovic M]] | ||
[[Category: Vinkovic | [[Category: Williams G]] | ||
[[Category: Williams | [[Category: Wyatt PG]] | ||
[[Category: Wyatt | |||