2pk9

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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=2pk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pk9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pk9 RCSB], [http://www.ebi.ac.uk/pdbsum/2pk9 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=2pk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pk9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pk9 RCSB], [http://www.ebi.ac.uk/pdbsum/2pk9 PDBsum]</span></td></tr>
</table>
</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/PHO85_YEAST PHO85_YEAST]] Cyclin-dependent protein kinase (CDK) catalytic subunit that regulates multiple cell cycle and metabolic processes in response to nutrient availability. Associates with different cyclins, that control kinase activity, substrate-specificity and subcellular location of the kinase. Favorable growth conditions always result in activated cyclin-CDK complexes. Regulates metabolic processes when associated with PHO80 cyclin family members (PH080, PCL6, PCL7, PCL8 and PCL10), and cell cycle and morphogenesis processes when associated with PCL1,2 cyclin family members (PCL1, PCL2, CLG1, PCL5 and PCL9). When associated with PHO80, negatively regulates the expression of phosphate-starvation-responsive genes under phosphate-rich conditions. The PHO80-PHO85 cyclin-CDK holoenzyme phosphorylates and inactivates the transcription factor PHO4 by promoting its export to the cytoplasm. PHO80-PHO85 phosphorylates and inactivates protein kinase RIM15 by retaining it in the cytoplasm, antagonizing RIM15-induced entry into stationary phase. PHO80-PHO85 also phosphorylates and inactivates the calcineurin-responsive transcription factor CRZ1, linking cyclin-CDK activity to calcium signaling. Together with the cyclins PCL6/PCL7 and PCL8/PCL10, negatively controls glycogen accumulation. When associated with cyclins PCL6 and PCL7, controls glycogen phosphorylase and glycogen synthase activities. PCL6-PHO85 and PCL7-PHO85 phosphorylate and inactivate the phosphatase PP1-2 inhibitor GLC8, causing activation of PP1-2, which then dephosphorylates and activates glycogen phosphorylase. When associated with cyclins PCL8 and PCL10, has glycogen synthase kinase activity. PCL10-PHO85 phosphorylates and negatively regulates glycogen synthase GSY2. Association with PCL1 and PCL2 is required for cell cycle progression at start in the absence of the CDC28-dependent G1 cyclins CLN1 and CLN2. PCL1-PHO85 is involved in phosphorylation of the CDK inhibitor (CKI) SIC1, which is required for its ubiquitination and degradation, releasing repression of b-type cyclins and promoting exit from mitosis. When associated with cyclins PCL1 and PCL2, positively controls degradation of sphingoid long chain base kinase LCB4 via phosphorylation of LCB4, which is required for its ubiquitination and degradation. PCL1-PHO85 also phosphorylates HMS1, NCP1 and NPA3, which may all have a role in mitotic exit. PCL2-PHO85 also phosphorylates RVS167, linking cyclin-CDK activity with organization of the actin cytoskeleton. When associated with PCL5, positively controls degradation of transcription factor GCN4 via phosphorylation of GCN4, which is required for its degradation by the E3 ubiquitin ligase complex SCF(Cdc4). When associated with PCL9, may have a role in bud site selection in G1 phase. PHO85 also phosphorylates the transcription factor SWI5.<ref>PMID:3067079</ref> <ref>PMID:8108735</ref> <ref>PMID:7973730</ref> <ref>PMID:8539622</ref> <ref>PMID:9843683</ref> <ref>PMID:9725902</ref> <ref>PMID:9584169</ref> <ref>PMID:9593297</ref> <ref>PMID:10490639</ref> <ref>PMID:10692159</ref> <ref>PMID:11602261</ref> <ref>PMID:12006994</ref> <ref>PMID:12098764</ref> <ref>PMID:12101234</ref> <ref>PMID:12407105</ref> <ref>PMID:12857883</ref> <ref>PMID:15057567</ref> <ref>PMID:15082539</ref> <ref>PMID:15721288</ref> <ref>PMID:16308562</ref> <ref>PMID:15598647</ref> <ref>PMID:16455487</ref> [[http://www.uniprot.org/uniprot/PHO80_YEAST PHO80_YEAST]] Cyclin partner of the cyclin-dependent kinase (CDK) PHO85. Negatively regulates the expression of phosphate-starvation-responsive genes under phosphate-rich conditions. The PHO80-PHO85 cyclin-CDK holoenzyme phosphorylates and inactivates the transcription factor PHO4, by preventing its association with the transcription factor PHO2 and the nuclear import receptor PSE1, and by promoting association with the nuclear export receptor MSN5, excluding PHO4 from the nucleus. PHO80-PHO85 phosphorylates and inactivates protein kinase RIM15 by retaining it in the cytoplasm, antagonizing RIM15-induced entry into stationary phase. PHO80-PHO85 also phosphorylates and inactivates the calcineurin-responsive transcription factor CRZ1, linking PHO85 to calcium signaling.<ref>PMID:16308562</ref> <ref>PMID:7957107</ref> <ref>PMID:8108735</ref> <ref>PMID:8539622</ref> <ref>PMID:9732266</ref> <ref>PMID:9853758</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Cyclin-dependent kinase]]
[[Category: Cyclin-dependent kinase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
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[[Category: Connell, I Ferrin-O.]]
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[[Category: Connell, I Ferrin-O]]
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[[Category: Huang, K.]]
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[[Category: Huang, K]]
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[[Category: Leonard, G A.]]
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[[Category: Leonard, G A]]
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[[Category: Quiocho, F A.]]
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[[Category: Quiocho, F A]]
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[[Category: Shea, E K.O.]]
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[[Category: Shea, E K.O]]
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[[Category: Zhang, W.]]
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[[Category: Zhang, W]]
[[Category: Cyclin]]
[[Category: Cyclin]]
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[[Category: Cyclin-dependent kinase]]
 
[[Category: Signaling protein]]
[[Category: Signaling protein]]
[[Category: Transferase- cell cycle complex]]
[[Category: Transferase- cell cycle complex]]
[[Category: Transferase-cell cycle complex]]
[[Category: Transferase-cell cycle complex]]

Revision as of 09:42, 25 December 2014

Structure of the Pho85-Pho80 CDK-cyclin Complex of the Phosphate-responsive Signal Transduction Pathway

2pk9, resolution 2.91Å

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