Switch #:
SWTI000293
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1).

Participants:
(1) Integrin beta-3 (ITGB3)
(2) Fermitin family homolog 2 (FERMT2)
(3) SHC-transforming protein 1 (SHC1)

Interactions
Interaction #1 ITGB3 - FERMT2

Is mutually exclusive with Interaction #2 ITGB3 - SHC1

Interfaces
(1) LIG_PTB_Apo_2 motif (779TFTNITYR786) in Integrin beta-3 (ITGB3)
(2) FERM central domain (281-573) in Fermitin family homolog 2 (FERMT2)

Interaction Regulation
PTM-dependent Abrogation (Phosphorylation of Y785 on Integrin beta-3 (ITGB3)) of the Integrin beta-3 (ITGB3) LIG_PTB_Apo_2 motif - Fermitin family homolog 2 (FERMT2) FERM central domain interaction

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

Interaction #2 ITGB3 - SHC1

Is mutually exclusive with Interaction #1 ITGB3 - FERMT2

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

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y785 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: 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
Inferred: cytosol, nucleus


Switch pathways
Inferred: Focal adhesion
References

(1) Tyrosine phosphorylation of integrin beta3 regulates kindlin-2 binding and integrin activation.
Bledzka et al. J. Biol. Chem. (2010)

(2) Kindlin-2 (Mig-2): a co-activator of beta3 integrins.
Ma et al. J. Cell Biol. (2008)

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




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