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Protein

Cyclin-dependent protein kinase PHO85

Gene

PHO85

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. 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 SWI5.22 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Inhibited by the CDK inhibitor (CKI) PHO81 in response to phosphate starvation.2 Publications

Kineticsi

  1. KM=1.5 µM for substrate protein GSY2 (when associated with cyclin PCL10)1 Publication
  1. Vmax=11.5 µmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei36ATPPROSITE-ProRule annotation1
Active sitei133Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi13 – 21ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: SGD
  • negative regulation of calcium-mediated signaling Source: SGD
  • negative regulation of glycogen biosynthetic process Source: SGD
  • negative regulation of macroautophagy Source: SGD
  • negative regulation of phosphate metabolic process Source: SGD
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: SGD
  • negative regulation of transcription from RNA polymerase II promoter Source: SGD
  • positive regulation of macroautophagy Source: SGD
  • protein phosphorylation Source: SGD
  • regulation of establishment or maintenance of cell polarity 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: SGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-33946-MONOMER.
BRENDAi2.7.11.22. 984.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent protein kinase PHO85 (EC:2.7.11.22)
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
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XVI

Organism-specific databases

EuPathDBiFungiDB:YPL031C.
SGDiS000005952. PHO85.

Subcellular locationi

GO - Cellular componenti

  • cyclin-dependent protein kinase holoenzyme complex Source: SGD
  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: SGD
  • Pho85-Pho80 CDK-cyclin complex Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18Y → F: Reduces kinase activity. Abolishes interaction to PHO80 cyclin, but not to PCL1. 1
Mutagenesisi36K → R: Loss of kinase activity. 1 Publication1
Mutagenesisi53E → A: Loss of kinase activity. Abolishes interaction to PHO80 and PCL1 cyclins. 1 Publication1
Mutagenesisi82F → 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 Publication1

Chemistry databases

ChEMBLiCHEMBL5589.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000865211 – 305Cyclin-dependent protein kinase PHO85Add BLAST305

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei18Phosphotyrosine1 Publication1
Cross-linki289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Combined sources

Post-translational modificationi

Phosphorylation of Tyr-18 seems to be important to discriminate between the different cyclin partners for binding.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei166Not phosphorylated1
Sitei167Not phosphorylated1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP17157.
PRIDEiP17157.

PTM databases

iPTMnetiP17157.

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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCL1P373662EBI-13327,EBI-4385
CLG1P351903EBI-13327,EBI-4762
CLN1P204372EBI-13327,EBI-4479
PCL1P248674EBI-13327,EBI-4495
PCL10P531247EBI-13327,EBI-23973
PCL2P256938EBI-13327,EBI-4499
PCL5P387942EBI-13327,EBI-4504
PCL6P400387EBI-13327,EBI-22555
PCL7P401869EBI-13327,EBI-25021
PCL8Q089669EBI-13327,EBI-37056
PCL9Q124774EBI-13327,EBI-38090
PHO80P200524EBI-13327,EBI-13310
PHO81P174425EBI-13327,EBI-13314
SSA1P105912EBI-13327,EBI-8591

Protein-protein interaction databases

BioGridi36147. 592 interactors.
DIPiDIP-1493N.
IntActiP17157. 30 interactors.
MINTiMINT-384508.

Chemistry databases

BindingDBiP17157.

Structurei

Secondary structure

1305
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 6Combined sources3
Beta strandi7 – 16Combined sources10
Beta strandi19 – 26Combined sources8
Turni27 – 29Combined sources3
Beta strandi32 – 39Combined sources8
Turni42 – 44Combined sources3
Helixi48 – 55Combined sources8
Turni56 – 59Combined sources4
Beta strandi68 – 74Combined sources7
Beta strandi77 – 83Combined sources7
Beta strandi86 – 88Combined sources3
Helixi89 – 94Combined sources6
Beta strandi98 – 100Combined sources3
Helixi107 – 126Combined sources20
Helixi136 – 138Combined sources3
Beta strandi139 – 141Combined sources3
Beta strandi147 – 149Combined sources3
Helixi152 – 154Combined sources3
Beta strandi156 – 160Combined sources5
Helixi172 – 174Combined sources3
Helixi177 – 180Combined sources4
Helixi189 – 204Combined sources16
Helixi214 – 225Combined sources12
Turni230 – 232Combined sources3
Helixi234 – 238Combined sources5
Beta strandi244 – 246Combined sources3
Helixi254 – 258Combined sources5
Helixi259 – 261Combined sources3
Helixi268 – 277Combined sources10
Helixi282 – 284Combined sources3
Helixi288 – 292Combined sources5
Helixi295 – 300Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PK9X-ray2.91A/C1-305[»]
2PMIX-ray2.90A/C1-305[»]
4KRCX-ray2.60A1-305[»]
4KRDX-ray1.95A1-305[»]
ProteinModelPortaliP17157.
SMRiP17157.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17157.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 297Protein kinasePROSITE-ProRule annotationAdd BLAST291

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00790000122986.
HOGENOMiHOG000233024.
InParanoidiP17157.
KOiK06655.
OMAiQVPQNAY.
OrthoDBiEOG092C2FL8.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17157-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:305
Mass (Da):34,906
Last modified:November 1, 1997 - v2
Checksum:i246A4358870B00EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99G → A in CAA68773 (PubMed:3320965).Curated1
Sequence conflicti99G → A in CAA68774 (PubMed:3320965).Curated1

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.
PIRiS62043. OKBY85.
RefSeqiNP_015294.1. NM_001183845.1.

Genome annotation databases

EnsemblFungiiYPL031C; YPL031C; YPL031C.
GeneIDi856076.
KEGGisce:YPL031C.

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.
PIRiS62043. OKBY85.
RefSeqiNP_015294.1. NM_001183845.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PK9X-ray2.91A/C1-305[»]
2PMIX-ray2.90A/C1-305[»]
4KRCX-ray2.60A1-305[»]
4KRDX-ray1.95A1-305[»]
ProteinModelPortaliP17157.
SMRiP17157.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi36147. 592 interactors.
DIPiDIP-1493N.
IntActiP17157. 30 interactors.
MINTiMINT-384508.

Chemistry databases

BindingDBiP17157.
ChEMBLiCHEMBL5589.

PTM databases

iPTMnetiP17157.

Proteomic databases

MaxQBiP17157.
PRIDEiP17157.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYPL031C; YPL031C; YPL031C.
GeneIDi856076.
KEGGisce:YPL031C.

Organism-specific databases

EuPathDBiFungiDB:YPL031C.
SGDiS000005952. PHO85.

Phylogenomic databases

GeneTreeiENSGT00790000122986.
HOGENOMiHOG000233024.
InParanoidiP17157.
KOiK06655.
OMAiQVPQNAY.
OrthoDBiEOG092C2FL8.

Enzyme and pathway databases

BioCyciYEAST:G3O-33946-MONOMER.
BRENDAi2.7.11.22. 984.

Miscellaneous databases

EvolutionaryTraceiP17157.
PROiP17157.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPHO85_YEAST
AccessioniPrimary (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: November 2, 2016
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 6160 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XVI
    Yeast (Saccharomyces cerevisiae) chromosome XVI: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.