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Switch #:
SWTI000351
Switch type:
Avidity-sensing

Description:
Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK).

Participants:
(1) Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A)
(2) Tyrosine-protein kinase SYK (SYK)

Interactions
Interaction #1 FCGR2A - SYK

Interfaces
(1) LIG_TYR_ITAM motif (285DGGYMTLNPRAPTDDDKNIYLTL307) in Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A)
(2) SH2 domain (15-92) in Tyrosine-protein kinase SYK (SYK)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y288 and Y304 on Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A)) of the Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) LIG_TYR_ITAM motif - Tyrosine-protein kinase SYK (SYK) SH2 domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y288 : Tyrosine-protein kinase Lyn (LYN), Tyrosine-protein kinase SYK (SYK), Tyrosine-protein kinase Blk (BLK), Tyrosine-protein kinase Fyn (FYN). Y304 : Tyrosine-protein kinase Fyn (FYN), Tyrosine-protein kinase Fyn (Fyn), Tyrosine-protein kinase Lyn (Lyn), Tyrosine-protein kinase Blk (BLK), Tyrosine-protein kinase Lyn (LYN), Tyrosine-protein kinase SYK (SYK).

Interaction #2 FCGR2A - SYK

Interfaces
(3) LIG_TYR_ITAM motif (285DGGYMTLNPRAPTDDDKNIYLTL307) in Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A)
(4) SH2 domain (168-244) in Tyrosine-protein kinase SYK (SYK)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y288 and Y304 on Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A)) of the Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) LIG_TYR_ITAM motif - Tyrosine-protein kinase SYK (SYK) SH2 domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: Y288 : Tyrosine-protein kinase Lyn (LYN), Tyrosine-protein kinase SYK (SYK), Tyrosine-protein kinase Blk (BLK), Tyrosine-protein kinase Fyn (FYN). Y304 : Tyrosine-protein kinase Fyn (FYN), Tyrosine-protein kinase Fyn (Fyn), Tyrosine-protein kinase Lyn (Lyn), Tyrosine-protein kinase Blk (BLK), Tyrosine-protein kinase Lyn (LYN), Tyrosine-protein kinase SYK (SYK).

Context
Switch localisation
Curated: cytoplasmic side of plasma membrane
ELM curated: cytosol


Switch pathways
Curated: Osteoclast differentiation, Fc gamma R-mediated phagocytosis
References

(1) Molecular mechanism of the Syk activation switch.
Tsang et al. J. Biol. Chem. (2008)

See also

Other switches involving participants
Tyrosine-protein kinase SYK (SYK) - 4 more (view)

Other switches involving interfaces
SH2 domain - 140 more (view)
LIG_TYR_ITAM - 8 more (view)


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