Curated Information
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Home > Curated Information Page > PubMed Id: 17574025
Wu RC, Feng Q, Lonard DM, O'Malley BW (2007) SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock. Cell 129, 1125-40 17574025
This page summarizes selected information from the record referenced above and curated into PhosphoSitePlus®, a comprehensive online resource for the study of protein post-translational modifications (NAR, 2015, 43:D512-20). To learn more about the scope of PhosphoSitePlus®, click here.
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S505-p - SRC-3 (human)
Modsite: SPVAGVHsPMAsSGN SwissProt Entrez-Gene
Orthologous residues
SRC‑3 (human): S505‑p, SRC‑3 iso2 (human): S505‑p, SRC‑3 (mouse): S498‑p, SRC‑3 (rat): S205‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), HeLa (cervical), MCF-7 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE GSK3A (human) transfection of wild-type enzyme, pharmacological inhibitor of upstream enzyme, siRNA inhibition of enzyme, transfection of inactive enzyme
Comments:  S509 is a priming site for phosphorylation of S505
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
Akt1 (human) decrease
lithium decrease
estradiol increase
EGF decrease
PD98059 EGF inhibit treatment-induced decrease
insulin decrease
LY294002 insulin inhibit treatment-induced decrease
Downstream Regulation
Effect of modification (function):  activity, induced, molecular association, regulation, protein degradation, ubiquitination
Effect of modification (process):  signaling pathway regulation, transcription, induced
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
ER-alpha (human) Induces activity, induced co-immunoprecipitation
Comments:  induces ubiquitination, degradation of SRC-3, and its interaction with ER.

S509-p - SRC-3 (human)
Modsite: GVHsPMAsSGNTGNH SwissProt Entrez-Gene
Orthologous residues
SRC‑3 (human): S509‑p, SRC‑3 iso2 (human): S509‑p, SRC‑3 (mouse): P502‑p, SRC‑3 (rat): S209‑p
Characterization
Methods used to characterize site in vivo mutation of modification site
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MCF-7 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE GSK3A (human) transfection of wild-type enzyme, pharmacological inhibitor of upstream enzyme, siRNA inhibition of enzyme, transfection of inactive enzyme
Comments:  S509 is a priming site for phosphorylation of S505
Downstream Regulation
Effect of modification (function):  activity, induced, molecular association, regulation, phosphorylation, protein degradation, ubiquitination
Effect of modification (process):  signaling pathway regulation, transcription, induced
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
ER-alpha (human) Induces activity, induced co-immunoprecipitation
Comments:  induces ubiquitination, degradation of SRC-3, and its interaction with ER., S509 is a priming site for phosphorylation of S505

K723-ub - SRC-3 (human)
Modsite: CGDGNVVkQEQLsPK SwissProt Entrez-Gene
Orthologous residues
SRC‑3 (human): K723‑ub, SRC‑3 iso2 (human): K723‑ub, SRC‑3 (mouse): R715‑ub, SRC‑3 (rat): X422‑ub
Characterization
Methods used to characterize site in vivo mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MCF-7 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Enzymes shown to modify site in vitro
Type Enzyme
UBIQUITIN LIGASE FBXW7 (human)
Downstream Regulation
Effect of modification (function):  activity, induced, molecular association, regulation, protein degradation, ubiquitination
Effect of modification (process):  signaling pathway regulation, transcription, induced
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
ER-alpha (human) Induces activity, induced co-immunoprecipitation
Comments:  induces ubiquitination, degradation of SRC-3, and its interaction with ER.

K786-ub - SRC-3 (human)
Modsite: QEKDPKIkTETSEEG SwissProt Entrez-Gene
Orthologous residues
SRC‑3 (human): K786‑ub, SRC‑3 iso2 (human): K786‑ub, SRC‑3 (mouse): K778‑ub, SRC‑3 (rat): K485‑ub
Characterization
Methods used to characterize site in vivo mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MCF-7 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Enzymes shown to modify site in vitro
Type Enzyme
UBIQUITIN LIGASE FBXW7 (human)
Downstream Regulation
Effect of modification (function):  activity, induced, molecular association, regulation, protein degradation, ubiquitination
Effect of modification (process):  signaling pathway regulation, transcription, induced
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
ER-alpha (human) Induces activity, induced co-immunoprecipitation
Comments:  induces ubiquitination, degradation of SRC-3, and its interaction with ER.