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Home > Curated Information Page > PubMed Id: 31340145
Nielsen CP, et al. (2019) USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification. Cell Rep 28, 1074-1089.e5 31340145
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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S142-p - DVL2 (human)
Modsite: sFHPNVSssHENLEP SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S142‑p, DVL2 (mouse): S142‑p, DVL2 (rat): S142‑p

S155-p - DVL2 (human)
Modsite: EPEtEtEsVVsLRRE SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S155‑p, DVL2 (mouse): S155‑p, DVL2 (rat): S155‑p

S169-p - DVL2 (human)
Modsite: ERPRRRDssEHGAGG SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S169‑p, DVL2 (mouse): S169‑p, DVL2 (rat): S169‑p

S170-p - DVL2 (human)
Modsite: RPRRRDssEHGAGGH SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S170‑p, DVL2 (mouse): S170‑p, DVL2 (rat): S170‑p

S211-p - DVL2 (human)
Modsite: EStSLGDsDEEDTMS SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S211‑p, DVL2 (mouse): S211‑p, DVL2 (rat): S211‑p

K343-ub - DVL2 (human)
Modsite: VLRDIVHkPGPIVLT SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): K343‑ub, DVL2 (mouse): K343‑ub, DVL2 (rat): K343‑ub
Characterization
Methods used to characterize site in vivo immunoprecipitation, mass spectrometry, microscopy-colocalization with upstream kinase, modification-specific antibody, mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MDA-MB-231 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
UBIQUITIN LIGASE WWP1 (human) co-immunoprecipitation
DEUBIQUITINASE USP9X (human) genetic knockout/knockin of upstream enzyme, co-immunoprecipitation catalytic activity of USP9X is required for canonical WNT activation
Downstream Regulation
Effect of modification (function):  intracellular localization, molecular association, regulation
Effect of modification (process):  cell motility, induced, signaling pathway regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
Cofilin-1 (human) Induces co-immunoprecipitation, microscopy-colocalization
VANGL1 (human) Induces co-immunoprecipitation
Comments:  DVL2 variant with all encoded lysine residues mutated to arginine is sufficient to restore WNT activation

K428-ub - DVL2 (human)
Modsite: TDMASVTkAMAAPEs SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): K428‑ub, DVL2 (mouse): K428‑ub, DVL2 (rat): K428‑ub
Characterization
Methods used to characterize site in vivo immunoprecipitation, mass spectrometry, microscopy-colocalization with upstream kinase, modification-specific antibody, mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MDA-MB-231 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
DEUBIQUITINASE USP9X (human) genetic knockout/knockin of upstream enzyme, co-immunoprecipitation catalytic activity of USP9X is required for canonical WNT activation
UBIQUITIN LIGASE WWP1 (human) co-immunoprecipitation
Downstream Regulation
Effect of modification (function):  intracellular localization, molecular association, regulation
Effect of modification (process):  cell motility, induced, signaling pathway regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
VANGL1 (human) Induces co-immunoprecipitation
Cofilin-1 (human) Induces co-immunoprecipitation, microscopy-colocalization
Comments:  DVL2 variant with all encoded lysine residues mutated to arginine is sufficient to restore WNT activation

K477-ub - DVL2 (human)
Modsite: PERREARkyASGLLk SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): K477‑ub, DVL2 (mouse): K477‑ub, DVL2 (rat): K477‑ub
Characterization
Methods used to characterize site in vivo immunoprecipitation, mass spectrometry, microscopy-colocalization with upstream kinase, modification-specific antibody, mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MDA-MB-231 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
UBIQUITIN LIGASE WWP1 (human) co-immunoprecipitation
DEUBIQUITINASE USP9X (human) genetic knockout/knockin of upstream enzyme, co-immunoprecipitation catalytic activity of USP9X is required for canonical WNT activation
Downstream Regulation
Effect of modification (function):  intracellular localization, molecular association, regulation
Effect of modification (process):  cell motility, induced, signaling pathway regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
VANGL1 (human) Induces co-immunoprecipitation
Cofilin-1 (human) Induces co-immunoprecipitation, microscopy-colocalization
Comments:  DVL2 variant with all encoded lysine residues mutated to arginine is sufficient to restore WNT activation

K484-ub - DVL2 (human)
Modsite: kyASGLLkAGLIRHT SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): K484‑ub, DVL2 (mouse): K484‑ub, DVL2 (rat): K484‑ub
Characterization
Methods used to characterize site in vivo immunoprecipitation, mass spectrometry, microscopy-colocalization with upstream kinase, modification-specific antibody, mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MDA-MB-231 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Downstream Regulation
Effect of modification (function):  intracellular localization, molecular association, regulation
Effect of modification (process):  cell motility, induced, signaling pathway regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
VANGL1 (human) Induces co-immunoprecipitation
Cofilin-1 (human) Induces co-immunoprecipitation, microscopy-colocalization
Comments:  DVL2 variant with all encoded lysine residues mutated to arginine is sufficient to restore WNT activation

S597-p - DVL2 (human)
Modsite: RssGstRsDGGAGRT SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S597‑p, DVL2 (mouse): S597‑p, DVL2 (rat): S597‑p

K615-ub - DVL2 (human)
Modsite: EERAPEskSGsGSES SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): K615‑ub, DVL2 (mouse): K615‑ub, DVL2 (rat): K615‑ub
Characterization
Methods used to characterize site in vivo immunoprecipitation, mass spectrometry, microscopy-colocalization with upstream kinase, modification-specific antibody, mutation of modification site, western blotting
Disease tissue studied:  breast cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), MDA-MB-231 (breast cell)
Cellular systems studied:  cell lines
Species studied:  human
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
DEUBIQUITINASE USP9X (human) genetic knockout/knockin of upstream enzyme, co-immunoprecipitation catalytic activity of USP9X is required for canonical WNT activation
UBIQUITIN LIGASE WWP1 (human) co-immunoprecipitation
Downstream Regulation
Effect of modification (function):  intracellular localization, molecular association, regulation
Effect of modification (process):  cell motility, induced, signaling pathway regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
VANGL1 (human) Induces co-immunoprecipitation
Cofilin-1 (human) Induces co-immunoprecipitation, microscopy-colocalization
Comments:  DVL2 variant with all encoded lysine residues mutated to arginine is sufficient to restore WNT activation

S618-p - DVL2 (human)
Modsite: APEskSGsGSESEPS SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): S618‑p, DVL2 (mouse): S618‑p, DVL2 (rat): S618‑p

T715-p - DVL2 (human)
Modsite: GSVPPELtASRQsFH SwissProt Entrez-Gene
Orthologous residues
DVL2 (human): T715‑p, DVL2 (mouse): T715‑p, DVL2 (rat): T715‑p