Table 1

A selected list of mammalian SH2 domains and their binding motifs. Listed here are mammalian SH2 domains, except for SPT6 from yeast, whose structures are currently available. Consensus motifs are based on results from (18), where pY denotes phosphotyrosine, x an undefined residue, ψ a hydrophobic residue, [-] an acidic residue, n/a not available.

GroupSH2 domainβD5OPAL motifPeptide specificity
residues
IIASRC, FYN, FRK, LCK, HCK, BLK,
ABL1, ABL2, ITK, BTK, TXK, ZAP70_N & C,
SYK_N & C, NCK1, NCK2, BRK
Y/FpY[-][-]ψP+3
IBSAP, EAT2, SHIP1, CRK, CRKL,
RasGAP_C, CHK (MATK)
Y/FpYxxψP+3
ICGRB2, GADS, GRB7, GRB10, GRB14,
ALX (HSH2D), FES, BMX, CSK, SH3BP2
Y/FpYxNP+2
IEα-Chimaerin, β-ChimaerinY/Fn/a?
IIIIAVAV, VAV2, PI3K-p85α_N & C, PLC-γ1_C,
PLC-γ2_N & C, SHP-1_N & C (PTPN6),
SHP-2_N & C (PTPN11), SOCS2, SOCS3, SOCS4, SOCS6
I/C/L/V/A/TpYψxψP+3
IIBAPS, SH2B, SHC1, BLNKL/IpY[E/D/x]xψP+3
IICBRDG1 (STAP-1), BKS (STAP-2), CBLY/TpYxxxψP+4
IIDSPT6VpY[P/I]P[K/R]M?
IIIIIISTAT1, STAT3, STAT5AV/LpYxxQ?*

*Because a STAT SH2 domain lacks an EF loop and has an open BG loop, it does not feature a conventional P+3 or P+4 binding pocket. A consensus motif listed here for the STAT3 SH2 domain is taken from (85). See (86) for a list of binding motifs of other STAT family SH2 domains.