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Switch #:
SWTI000281
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN).

Participants:
(1) Dystroglycan (DAG1)
(2) Dystrophin (DMD)
(3) Tyrosine-protein kinase Fyn (FYN)

Interactions
Interaction #1 DAG1 - DMD

Is mutually exclusive with Interaction #2 DAG1 - FYN

Interfaces
(1) LIG_WW_1 motif (889PPPY892) in Dystroglycan (DAG1)
(2) WW domain (3057-3086) in Dystrophin (DMD)

Interaction Regulation
PTM-dependent Abrogation (Phosphorylation of Y892 on Dystroglycan (DAG1)) of the Dystroglycan (DAG1) LIG_WW_1 motif - Dystrophin (DMD) WW domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y892 : Proto-oncogene tyrosine-protein kinase Src (SRC).

Additional Information
Structural information: 1EG4
Interaction #2 DAG1 - FYN

Is mutually exclusive with Interaction #1 DAG1 - DMD

Interfaces
(3) LIG_SH2_SRC motif (892YVPP895) in Dystroglycan (DAG1)
(4) SH2 domain (149-231) in Tyrosine-protein kinase Fyn (FYN)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y892 on Dystroglycan (DAG1)) of the Dystroglycan (DAG1) LIG_SH2_SRC motif - Tyrosine-protein kinase Fyn (FYN) SH2 domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y892 : Proto-oncogene tyrosine-protein kinase Src (SRC).

Context
Switch localisation
ELM curated: cytosol, integral membrane protein, integral plasma membrane protein
Inferred: cytoskeleton, sarcolemma, cytosol, dystrophin-associated glycoprotein complex, costamere
References

(1) Dystroglycan versatility in cell adhesion: a tale of multiple motifs.
Moore et al. Cell Commun. Signal (2010)

(2) Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins.
Sotgia et al. Biochemistry (2001)

See also

Other switches involving participants
Dystroglycan (DAG1) - 3 more (view)
Tyrosine-protein kinase Fyn (FYN) - 1 more (view)
Dystrophin (DMD) - 2 more (view)

Other switches involving interfaces
SH2 domain - 140 more (view)
WW domain - 105 more (view)
LIG_SH2_SRC - 8 more (view)
LIG_WW_1 - 17 more (view)


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