About Help Definitions Submit Search Analyse Browse Home


Switch #:
SWTI000277
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation.

Participants:
(1) Integrin beta-3 (ITGB3)
(2) Talin-1 (TLN1)
(3) Docking protein 1 (DOK1)

Interactions
Interaction #1 ITGB3 - TLN1

Is mutually exclusive with Interaction #2 ITGB3 - DOK1

Interfaces
(1) LIG_PTB_Apo_2 motif (767TANNPLYK774) in Integrin beta-3 (ITGB3)
(2) PTB domain (IRS-1 type) (310-401) in Talin-1 (TLN1)

Interaction Regulation
PTM-dependent Inhibition (Phosphorylation of Y773 on Integrin beta-3 (ITGB3)) of the Integrin beta-3 (ITGB3) LIG_PTB_Apo_2 motif - Talin-1 (TLN1) PTB domain (IRS-1 type) interaction

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

Additional Information
Affinity : Y773: 3490 µM, pY773: 6530 µM
Interaction #2 ITGB3 - DOK1

Is mutually exclusive with Interaction #1 ITGB3 - TLN1

Interfaces
(3) LIG_PTB_Phospho_1 motif (767TANNPLY773) in Integrin beta-3 (ITGB3)
(4) PTB domain (IRS-1 type) (151-254) in Docking protein 1 (DOK1)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y773 on Integrin beta-3 (ITGB3)) of the Integrin beta-3 (ITGB3) LIG_PTB_Phospho_1 motif - Docking protein 1 (DOK1) PTB domain (IRS-1 type) interaction

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

Additional Information
Affinity : Y773: 14300 µM, pY773: 37 µM
Context
Switch localisation
ELM curated: integrin, cytoplasmic membrane-bounded vesicle, cytosol, internal side of plasma membrane, receptor complex
Inferred: cytosol


Switch pathways
Inferred: Focal adhesion
References

(1) An integrin phosphorylation switch: the effect of beta3 integrin tail phosphorylation on Dok1 and talin binding.
Oxley et al. J. Biol. Chem. (2008)

See also

Other switches involving participants
Docking protein 1 (DOK1) - 4 more (view)
Integrin beta-3 (ITGB3) - 15 more (view)
Talin-1 (TLN1) - 3 more (view)

Other switches involving interfaces
PTB domain (IRS-1 type) - 12 more (view)
LIG_PTB_Phospho_1 - 18 more (view)
LIG_PTB_Apo_2 - 3 more (view)


Loading visualisation

           
Please send any suggestions/comments to: switches@elm.eu.org