Switches.ELM

Switch #:

SWTI000275

Switch type:
Cumulative

Switch subtype:
Rheostatic

Description:
While phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to SHC-transforming protein 1 (SHC1), additional phosphorylation of Y773 further increases the strength of the interaction.

Participants:
(1) Integrin beta-3 (ITGB3)
(2) SHC-transforming protein 1 (SHC1)

Interactions

Interaction #1 ITGB3 - SHC1

Interfaces
(1) LIG_PTB_Phospho_1 motif (₇₇₉TFTNITY₇₈₅) in Integrin beta-3 (ITGB3)
(2) Phosphotyrosine interaction domain (PTB/PID)_(162-318) in SHC-transforming protein 1 (SHC1)

Interaction Regulation
PTM-dependent Enhancement (Phosphorylation of Y₇₈₅ and Y₇₇₃ on Integrin beta-3 (ITGB3)) of the Integrin beta-3 (ITGB3) LIG_PTB_Phospho_1 motif - SHC-transforming protein 1 (SHC1) Phosphotyrosine interaction domain (PTB/PID) interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y₇₇₃ : Proto-oncogene tyrosine-protein kinase Src (SRC). Y₇₈₅ : Tyrosine-protein kinase SYK (SYK), Proto-oncogene tyrosine-protein kinase Src (SRC).

Additional Information
Structural information: 2L1C

Context

Switch localisation
ELM curated: integrin, cytoplasmic membrane-bounded vesicle, cytosol, internal side of plasma membrane, receptor complex

Switch pathways

Inferred: Focal adhesion

References

(1) Identification of shc as the primary protein binding to the tyrosine-phosphorylated beta 3 subunit of alpha IIbbeta 3 during outside-in integrin platelet signaling.
Cowan et al. J. Biol. Chem. (2000)

(2) Integrin {beta}3 phosphorylation dictates its complex with the Shc phosphotyrosine-binding (PTB) domain.
Deshmukh et al. J. Biol. Chem. (2010)