1wcc: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1wcc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WCC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WCC FirstGlance]. <br> | <table><tr><td colspan='2'>[[1wcc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WCC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WCC FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIG:2-AMINO-6-CHLOROPYRAZINE'>CIG</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIG:2-AMINO-6-CHLOROPYRAZINE'>CIG</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aq1|1aq1]], [[1b38|1b38]], [[1b39|1b39]], [[1buh|1buh]], [[1ckp|1ckp]], [[1di8|1di8]], [[1dm2|1dm2]], [[1e1v|1e1v]], [[1e1x|1e1x]], [[1e9h|1e9h]], [[1f5q|1f5q]], [[1fin|1fin]], [[1fq1|1fq1]], [[1fvt|1fvt]], [[1fvv|1fvv]], [[1g5s|1g5s]], [[1gih|1gih]], [[1gii|1gii]], [[1gij|1gij]], [[1gy3|1gy3]], [[1gz8|1gz8]], [[1h00|1h00]], [[1h01|1h01]], [[1h07|1h07]], [[1h08|1h08]], [[1h0v|1h0v]], [[1h0w|1h0w]], [[1h1p|1h1p]], [[1h1q|1h1q]], [[1h1r|1h1r]], [[1h1s|1h1s]], [[1h24|1h24]], [[1h25|1h25]], [[1h26|1h26]], [[1h27|1h27]], [[1h28|1h28]], [[1hck|1hck]], [[1hcl|1hcl]], [[1jst|1jst]], [[1jsu|1jsu]], [[1jsv|1jsv]], [[1jvp|1jvp]], [[1ke5|1ke5]], [[1ke6|1ke6]], [[1ke7|1ke7]], [[1ke8|1ke8]], [[1ke9|1ke9]], [[1ogu|1ogu]], [[1oi9|1oi9]], [[1oiq|1oiq]], [[1oir|1oir]], [[1oit|1oit]], [[1oiu|1oiu]], [[1oiy|1oiy]], [[1oku|1oku]], [[1okv|1okv]], [[1okw|1okw]], [[1ol1|1ol1]], [[1ol2|1ol2]], [[1p2a|1p2a]], [[1p5e|1p5e]], [[1pf8|1pf8]], [[1pkd|1pkd]], [[1pw2|1pw2]], [[1pxi|1pxi]], [[1pxj|1pxj]], [[1pxk|1pxk]], [[1pxl|1pxl]], [[1pxm|1pxm]], [[1pxn|1pxn]], [[1pxo|1pxo]], [[1pxp|1pxp]], [[1pye|1pye]], [[1qmz|1qmz]], [[1r78|1r78]], [[1urc|1urc]], [[1urw|1urw]], [[1v1k|1v1k]], [[1vyw|1vyw]], [[1vyz|1vyz]], [[1w0x|1w0x]], [[1w8c|1w8c]], [[1w98|1w98]], [[2bhe|2bhe]], [[2bhh|2bhh]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aq1|1aq1]], [[1b38|1b38]], [[1b39|1b39]], [[1buh|1buh]], [[1ckp|1ckp]], [[1di8|1di8]], [[1dm2|1dm2]], [[1e1v|1e1v]], [[1e1x|1e1x]], [[1e9h|1e9h]], [[1f5q|1f5q]], [[1fin|1fin]], [[1fq1|1fq1]], [[1fvt|1fvt]], [[1fvv|1fvv]], [[1g5s|1g5s]], [[1gih|1gih]], [[1gii|1gii]], [[1gij|1gij]], [[1gy3|1gy3]], [[1gz8|1gz8]], [[1h00|1h00]], [[1h01|1h01]], [[1h07|1h07]], [[1h08|1h08]], [[1h0v|1h0v]], [[1h0w|1h0w]], [[1h1p|1h1p]], [[1h1q|1h1q]], [[1h1r|1h1r]], [[1h1s|1h1s]], [[1h24|1h24]], [[1h25|1h25]], [[1h26|1h26]], [[1h27|1h27]], [[1h28|1h28]], [[1hck|1hck]], [[1hcl|1hcl]], [[1jst|1jst]], [[1jsu|1jsu]], [[1jsv|1jsv]], [[1jvp|1jvp]], [[1ke5|1ke5]], [[1ke6|1ke6]], [[1ke7|1ke7]], [[1ke8|1ke8]], [[1ke9|1ke9]], [[1ogu|1ogu]], [[1oi9|1oi9]], [[1oiq|1oiq]], [[1oir|1oir]], [[1oit|1oit]], [[1oiu|1oiu]], [[1oiy|1oiy]], [[1oku|1oku]], [[1okv|1okv]], [[1okw|1okw]], [[1ol1|1ol1]], [[1ol2|1ol2]], [[1p2a|1p2a]], [[1p5e|1p5e]], [[1pf8|1pf8]], [[1pkd|1pkd]], [[1pw2|1pw2]], [[1pxi|1pxi]], [[1pxj|1pxj]], [[1pxk|1pxk]], [[1pxl|1pxl]], [[1pxm|1pxm]], [[1pxn|1pxn]], [[1pxo|1pxo]], [[1pxp|1pxp]], [[1pye|1pye]], [[1qmz|1qmz]], [[1r78|1r78]], [[1urc|1urc]], [[1urw|1urw]], [[1v1k|1v1k]], [[1vyw|1vyw]], [[1vyz|1vyz]], [[1w0x|1w0x]], [[1w8c|1w8c]], [[1w98|1w98]], [[2bhe|2bhe]], [[2bhh|2bhh]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wcc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wcc RCSB], [http://www.ebi.ac.uk/pdbsum/1wcc PDBsum]</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=1wcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wcc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wcc RCSB], [http://www.ebi.ac.uk/pdbsum/1wcc PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[[http://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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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Cleasby, A | [[Category: Cleasby, A]] | ||
[[Category: Frederickson, M | [[Category: Frederickson, M]] | ||
[[Category: Hartshorn, M J | [[Category: Hartshorn, M J]] | ||
[[Category: Jhoti, H | [[Category: Jhoti, H]] | ||
[[Category: Murray, C W | [[Category: Murray, C W]] | ||
[[Category: Reilly, M O | [[Category: Reilly, M O]] | ||
[[Category: Tickle, I J | [[Category: Tickle, I J]] | ||
[[Category: Cdk2]] | [[Category: Cdk2]] | ||
[[Category: Cell cycle]] | [[Category: Cell cycle]] | ||