UniProtKB - P17157 (PHO85_YEAST)
Cyclin-dependent protein kinase PHO85
PHO85
Functioni
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. 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) (PubMed:10490639, PubMed:10692159, PubMed:11602261, PubMed:12006994, PubMed:12098764, PubMed:12101234, PubMed:12407105, PubMed:12857883, PubMed:15057567, PubMed:15082539, PubMed:15598647, PubMed:15721288, PubMed:16308562, PubMed:16455487, PubMed:3067079, PubMed:7973730, PubMed:8108735, PubMed:8539622, PubMed:9584169, PubMed:9593297, PubMed:9725902, PubMed:9843683, PubMed:12455686).
When associated with PHO80, negatively regulates the expression of phosphate-starvation-responsive genes under phosphate-rich conditions (PubMed:8108735, PubMed:3067079).
The PHO80-PHO85 cyclin-CDK holoenzyme phosphorylates and inactivates the transcription factor PHO4 by promoting its export to the cytoplasm (PubMed:8108735).
PHO80-PHO85 phosphorylates and inactivates protein kinase RIM15 by retaining it in the cytoplasm, antagonizing RIM15-induced entry into stationary phase (PubMed:16308562).
PHO80-PHO85 also phosphorylates and inactivates the calcineurin-responsive transcription factor CRZ1, linking cyclin-CDK activity to calcium signaling (PubMed:16455487).
PHO80-PHO85 phosphorylates MMR1 (PubMed:12006994).
Together with the cyclins PCL6/PCL7 and PCL8/PCL10, negatively controls glycogen accumulation (PubMed:10490639, PubMed:11602261, PubMed:15721288, PubMed:8539622, PubMed:9584169, PubMed:12407105).
When associated with cyclins PCL6 and PCL7, controls glycogen phosphorylase and glycogen synthase activities (PubMed:11602261, PubMed:15721288, PubMed:12407105).
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 (PubMed:12407105).
PCL7-PHO85 phosphorylate ALY2 (PubMed:12098764).
PCL10-PHO85 phosphorylates and negatively regulates glycogen synthase GSY2 (PubMed:9584169).
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 (PubMed:7973730, PubMed:7973731).
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 (PubMed:9725902).
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 (PubMed:15598647).
PCL1-PHO85 also phosphorylates HMS1, NCP1 and NPA3, which may all have a role in mitotic exit (PubMed:15082539).
PCL2-PHO85 also phosphorylates RVS167, linking cyclin-CDK activity with organization of the actin cytoskeleton (PubMed:9843683, PubMed:12857883).
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) (PubMed:12455686, PubMed:12101234).
When associated with PCL9, may have a role in bud site selection in G1 phase (PubMed:9593297).
PHO85 also phosphorylates the transcription factor SWI5 (PubMed:10692159).
24 PublicationsMiscellaneous
Catalytic activityi
Activity regulationi
Kineticsi
- KM=1.5 µM for substrate protein GSY2 (when associated with cyclin PCL10)1 Publication
- Vmax=11.5 µmol/min/mg enzyme1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 36 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 133 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 13 – 21 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cyclin-dependent protein serine/threonine kinase activity Source: SGD
- protein kinase activity Source: SGD
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cellular response to DNA damage stimulus Source: SGD
- fungal-type cell wall organization Source: SGD
- lipid homeostasis Source: SGD
- negative regulation of calcium-mediated signaling Source: SGD
- negative regulation of DNA-binding transcription factor activity Source: ComplexPortal
- negative regulation of glycogen biosynthetic process Source: SGD
- negative regulation of macroautophagy Source: SGD
- negative regulation of phosphate metabolic process Source: ComplexPortal
- negative regulation of transcription by RNA polymerase II Source: SGD
- positive regulation of macroautophagy Source: SGD
- positive regulation of phospholipid biosynthetic process Source: SGD
- protein phosphorylation Source: SGD
- regulation of cell cycle phase transition Source: SGD
- regulation of cell division Source: ComplexPortal
- regulation of establishment or maintenance of cell polarity Source: SGD
- regulation of lipid metabolic process Source: SGD
- regulation of nucleocytoplasmic transport Source: SGD
- regulation of protein localization Source: SGD
- regulation of protein stability Source: SGD
- regulation of transcription involved in G1/S transition of mitotic cell cycle Source: ComplexPortal
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.22, 984 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclin-dependent protein kinase PHO85 (EC:2.7.11.225 Publications)Alternative name(s): Negative regulator of the PHO system Serine/threonine-protein kinase PHO85 |
Gene namesi | Name:PHO85 Synonyms:SSG3 Ordered Locus Names:YPL031C ORF Names:P7102.18A |
Organismi | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
Taxonomic identifieri | 559292 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › |
Proteomesi |
|
Organism-specific databases
SGDi | S000005952, PHO85 |
VEuPathDBi | FungiDB:YPL031C |
Subcellular locationi
Nucleus
- nucleus Source: SGD
Other locations
- cellular bud neck Source: ComplexPortal
- cyclin-dependent protein kinase holoenzyme complex Source: SGD
- cytoplasm Source: GO_Central
- Pho85-Pho80 CDK-cyclin complex Source: SGD
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 18 | Y → F: Reduces kinase activity. Abolishes interaction to PHO80 cyclin, but not to PCL1. | 1 | |
Mutagenesisi | 36 | K → R: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 53 | E → A: Loss of kinase activity. Abolishes interaction to PHO80 and PCL1 cyclins. 1 Publication | 1 | |
Mutagenesisi | 82 | F → G: Functional kinase, that can be rapidly inhibited by small, cell-permeable drugs like 1-Na PP1 (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine). 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL5589 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086521 | 1 – 305 | Cyclin-dependent protein kinase PHO85Add BLAST | 305 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 18 | Phosphotyrosine1 Publication | 1 | |
Cross-linki | 289 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 166 | Not phosphorylated1 Publication | 1 | |
Sitei | 167 | Not phosphorylated1 Publication | 1 |
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | P17157 |
PaxDbi | P17157 |
PRIDEi | P17157 |
PTM databases
iPTMneti | P17157 |
Interactioni
Subunit structurei
Monomer.
Forms a cyclin-CDK complex with at least 10 different cyclin partners: PCL1, PCL2, PHO80, CLG1, PCL5, PCL6, PCL7, PCL8, PCL9 and PCL10.
Interacts with GLC8 and RIM15.
9 PublicationsBinary interactionsi
P17157
Protein-protein interaction databases
BioGRIDi | 36147, 661 interactors |
ComplexPortali | CPX-1688, PHO80-PHO85 kinase complex CPX-1689, PCL6-PHO85 kinase complex CPX-1690, PCL7-PHO85 kinase complex CPX-1691, PCL8-PHO85 kinase complex CPX-1692, PCL10-PHO85 kinase complex CPX-1693, CLG1-PHO85 kinase complex CPX-1694, PCL2-PHO85 kinase complex CPX-1695, PCL1-PHO85 kinase complex CPX-1696, PCL5-PHO85 kinase complex CPX-1697, PCL9-PHO85 kinase complex |
DIPi | DIP-1493N |
IntActi | P17157, 58 interactors |
MINTi | P17157 |
STRINGi | 4932.YPL031C |
Chemistry databases
BindingDBi | P17157 |
Miscellaneous databases
RNActi | P17157, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P17157 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P17157 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 7 – 297 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 291 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0594, Eukaryota |
GeneTreei | ENSGT00940000173166 |
HOGENOMi | CLU_000288_181_1_1 |
InParanoidi | P17157 |
OMAi | QHPWFND |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSSSSQFKQL EKLGNGTYAT VYKGLNKTTG VYVALKEVKL DSEEGTPSTA
60 70 80 90 100
IREISLMKEL KHENIVRLYD VIHTENKLTL VFEFMDNDLK KYMDSRTVGN
110 120 130 140 150
TPRGLELNLV KYFQWQLLQG LAFCHENKIL HRDLKPQNLL INKRGQLKLG
160 170 180 190 200
DFGLARAFGI PVNTFSSEVV TLWYRAPDVL MGSRTYSTSI DIWSCGCILA
210 220 230 240 250
EMITGKPLFP GTNDEEQLKL IFDIMGTPNE SLWPSVTKLP KYNPNIQQRP
260 270 280 290 300
PRDLRQVLQP HTKEPLDGNL MDFLHGLLQL NPDMRLSAKQ ALHHPWFAEY
YHHAS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 99 | G → A in CAA68773 (PubMed:3320965).Curated | 1 | |
Sequence conflicti | 99 | G → A in CAA68774 (PubMed:3320965).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y00867 Genomic DNA Translation: CAA68773.1 Y00867 Genomic DNA Translation: CAA68774.1 Sequence problems. U44030 Genomic DNA Translation: AAB68188.1 BK006949 Genomic DNA Translation: DAA11398.1 |
PIRi | S62043, OKBY85 |
RefSeqi | NP_015294.1, NM_001183845.1 |
Genome annotation databases
EnsemblFungii | YPL031C_mRNA; YPL031C; YPL031C |
GeneIDi | 856076 |
KEGGi | sce:YPL031C |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y00867 Genomic DNA Translation: CAA68773.1 Y00867 Genomic DNA Translation: CAA68774.1 Sequence problems. U44030 Genomic DNA Translation: AAB68188.1 BK006949 Genomic DNA Translation: DAA11398.1 |
PIRi | S62043, OKBY85 |
RefSeqi | NP_015294.1, NM_001183845.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2PK9 | X-ray | 2.91 | A/C | 1-305 | [»] | |
2PMI | X-ray | 2.90 | A/C | 1-305 | [»] | |
4KRC | X-ray | 2.60 | A | 1-305 | [»] | |
4KRD | X-ray | 1.95 | A | 1-305 | [»] | |
SMRi | P17157 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 36147, 661 interactors |
ComplexPortali | CPX-1688, PHO80-PHO85 kinase complex CPX-1689, PCL6-PHO85 kinase complex CPX-1690, PCL7-PHO85 kinase complex CPX-1691, PCL8-PHO85 kinase complex CPX-1692, PCL10-PHO85 kinase complex CPX-1693, CLG1-PHO85 kinase complex CPX-1694, PCL2-PHO85 kinase complex CPX-1695, PCL1-PHO85 kinase complex CPX-1696, PCL5-PHO85 kinase complex CPX-1697, PCL9-PHO85 kinase complex |
DIPi | DIP-1493N |
IntActi | P17157, 58 interactors |
MINTi | P17157 |
STRINGi | 4932.YPL031C |
Chemistry databases
BindingDBi | P17157 |
ChEMBLi | CHEMBL5589 |
PTM databases
iPTMneti | P17157 |
Proteomic databases
MaxQBi | P17157 |
PaxDbi | P17157 |
PRIDEi | P17157 |
Genome annotation databases
EnsemblFungii | YPL031C_mRNA; YPL031C; YPL031C |
GeneIDi | 856076 |
KEGGi | sce:YPL031C |
Organism-specific databases
SGDi | S000005952, PHO85 |
VEuPathDBi | FungiDB:YPL031C |
Phylogenomic databases
eggNOGi | KOG0594, Eukaryota |
GeneTreei | ENSGT00940000173166 |
HOGENOMi | CLU_000288_181_1_1 |
InParanoidi | P17157 |
OMAi | QHPWFND |
Enzyme and pathway databases
BRENDAi | 2.7.11.22, 984 |
Miscellaneous databases
EvolutionaryTracei | P17157 |
PROi | PR:P17157 |
RNActi | P17157, protein |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PHO85_YEAST | |
Accessioni | P17157Primary (citable) accession number: P17157 Secondary accession number(s): D6W3Y2, Q03089, Q06888 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | November 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 206 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Yeast
Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD - Yeast chromosome XVI
Yeast (Saccharomyces cerevisiae) chromosome XVI: entries and gene names - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families