Table 3.

Overlap between SMALI-predicted SH2-ligand interactions and those listed in PPI databases

SH2 domain classificationa	SH2-containing proteins	SH2-interacting proteins predicted by SMALIb	SH2-interacting proteins included in PPI databasesc	Intersection between SMALI and PPI spaced	Overlap of SMALI network with PPI databases (%)e	Statistical significance of overlapf (P-value)
IA	SRC	298	104	63	15 (23.8)	<0.0004
IA	LYN	204	69	50	13 (26.0)	<0.00001
IA	ABL1	253	63	46	11 (23.9)	<0.0006
IA	FYN	313	99	69	14 (20.3)	<0.006
IB	CRK	395	44	35	14 (40.0)	<0.00005
IB	CRKL	274	40	30	9 (30)	<0.0006
IC	GRB2	420	383	250	68 (27.2)	<0.00001
IC	GRAP2	308	27	18	7 (38.9)	<0.0009
IIA	PIK3R1	317	98	73	35 (49.3)	<0.00001
IIA	PTPN11	288	67	59	20 (33.9)	<0.00001
IIA	VAV1	170	54	45	13 (28.9)	<0.00001
IIB	SHC1	275	98	77	22 (28.6)	<0.00001

^aThe SH2 domain classification is based on (13). Group IA has a common motif poY−−φ, IB has poYxxφ, IC has poYxNx, IIA has poYφxφ and IIB has the motif poY[E/D/x]xφ, where ‘−’ denotes a negatively charged residue, φ denotes a hydrophobic residue and x is any type of residues.

^bNumber of proteins predicted to bind to a specific SH2 domain-containing protein in the table by SMALI with a relative score >1.0. The Phosphorylation filter is applied with the prediction.

^cNumber of binding proteins for a specific SH2-containing protein according to PPI databases I2D (24) and IntAct (22).

^dSMALI space is the number of proteins (3253) used in the prediction. These include all proteins listed in the PhosphoSite and Phospho.ELM databases that contain a pTyr. Intersection is defined as the protein space covered by both SMALI and the PPI databases.

^eNumber of common interactions shared between the PPI databases and SMALI prediction for a given SH2-containing protein. The percentage of overlap (in parenthesis) is calculated by dividing this number by the intersected space between PPI and SMALI.

^fObserved overlap over that expected by chance.