2bpm: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='2bpm' size='340' side='right'caption='[[2bpm]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='2bpm' size='340' side='right'caption='[[2bpm]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2bpm]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2bpm]] 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=2BPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BPM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=529:(2S)-N-[(3Z)-5-CYCLOPROPYL-3H-PYRAZOL-3-YLIDENE]-2-[4-(2-OXOIMIDAZOLIDIN-1-YL)PHENYL]PROPANAMIDE'>529</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=529:(2S)-N-[(3Z)-5-CYCLOPROPYL-3H-PYRAZOL-3-YLIDENE]-2-[4-(2-OXOIMIDAZOLIDIN-1-YL)PHENYL]PROPANAMIDE'>529</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2bpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bpm OCA], [https://pdbe.org/2bpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bpm RCSB], [https://www.ebi.ac.uk/pdbsum/2bpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bpm ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 36: | Line 37: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Albanese C]] | |||
[[Category: Albanese | [[Category: Alzani R]] | ||
[[Category: Alzani | [[Category: Bischoff JR]] | ||
[[Category: Bischoff | [[Category: Brasca MG]] | ||
[[Category: Brasca | [[Category: Cameron A]] | ||
[[Category: Cameron | [[Category: Ciomei M]] | ||
[[Category: Ciomei | [[Category: Fiorentini F]] | ||
[[Category: Fiorentini | [[Category: Fogliatto G]] | ||
[[Category: Fogliatto | [[Category: Longo A]] | ||
[[Category: Longo | [[Category: Marsiglio A]] | ||
[[Category: Marsiglio | [[Category: Mercurio C]] | ||
[[Category: Mercurio | [[Category: Nesi M]] | ||
[[Category: Nesi | [[Category: Orsini P]] | ||
[[Category: Orsini | [[Category: Orzi F]] | ||
[[Category: Orzi | [[Category: Pastori W]] | ||
[[Category: Pastori | [[Category: Pesenti E]] | ||
[[Category: Pesenti | [[Category: Pevarello P]] | ||
[[Category: Pevarello | [[Category: Piutti C]] | ||
[[Category: Piutti | [[Category: Roletto F]] | ||
[[Category: Roletto | [[Category: Sansonna P]] | ||
[[Category: Sansonna | [[Category: Traquandi G]] | ||
[[Category: Traquandi | [[Category: Varasi M]] | ||
[[Category: Varasi | [[Category: Vulpetti A]] | ||
[[Category: Vulpetti | |||