Table 1.
The 38 SH2 families. All 111 human SH2 domain proteins were cataloged into 38 distinct SH2 families by means of sequence alignments, domain organization, and intron/exon splicing. For each family we determined whether an individual approach would be sufficient to categorize a family (Yes or No). If a method failed to classify a family, we noted the reason(s) in the comments column.
| Family | Human gene names | Sequence alignment |
Domain organization |
Splice sites | Comments |
|---|---|---|---|---|---|
| ABL | ABL1, ABL2 | Yes | Yes | Yes | |
| CBL | CBL, CBLB, CBLC | Yes | No | Yes | CBLC lacks a UBA domain |
| CHN | CHN1, CHN2 | Yes | Yes | Yes | |
| CRK | CRK, CRKL | Yes | Yes | No | Different splice sites |
| CSK | CSK, MATK | Yes | No | Yes | Same domain organization as SRC and FRK |
| DAPP1 | DAPP1 | Yes | Yes | Yes | |
| FPS | FES, FER | Yes | Yes | Yes | |
| FRK | FRK, BRK, SRMS | No | No | Yes | FRK aligns with SRC, similar domain organization to Src, Csk, Txk |
| GRB | GRB2, GADS, GRAP | Yes | Yes | No | Shares same splice patterns as SHB |
| GRB7 | GRB7, GRB10, GRB14 | Yes | Yes | Yes | |
| JAK | TYK2, JAK1, JAK2, JAK3 | Yes | Yes | Yes | |
| NCK | NCK1, NCK2 | Yes | Yes | Yes | |
| PI3KR | PIK3R1, PIK3R2, PIK3R3 | Yes | No | Yes | PIK3R3 lacks an SH3 and a RhoGAP domain |
| PLCγ | PLCG1, PLCG2 | Yes | Yes | Yes | |
| PTPN | PTPN6, PTPN11 | Yes | Yes | Yes | |
| RASA1 | RASA1 | Yes | Yes | Yes | |
| RIN | RIN1, RIN2, RIN3 | Yes | Yes | Yes | |
| SH2B | APS, LNK, SH2B | Yes | No | Yes | Same domain organization as SH3BP2 and STAP |
| SH2D1 | SH2D1A, SH2D1B | Yes | Yes | No | Shares same splice patterns as SHIP |
| SH2D2 | SH2D2A, HSH2, SH2D7 | Yes | Yes | Yes | |
| SH2D3 | SH2D3A, SH2D3C, BCAR3 | Yes | Yes | Yes | |
| SH2D4 | SH2D4A, SH2D4B | Yes | Yes | Yes | |
| SH2D5 | SH2D5 | Yes | No | Yes | Same domain organization as SHC |
| SH3BP2 | SH3BP2 | Yes | No | Yes | Same domain organization as STAP and SH2B |
| SHB | SHB, SHD, SHE, SHF | Yes | Yes | No | Shares same splice patterns as GRB2 |
| SHC | SHC1, SHC2, SHC3, SHC4 | Yes | No | Yes | Shares the same domain organization as SH2D5 |
| SHIP | SHIP1, SHIP2 | Yes | No | No | SHIP2 contains a SAM domain, shares the same splice pattern as SH2D1 |
| SLAP | SLAP, SLAP2 | No | Yes | No | SLAP and SLAP2 share sequence similarity to SRC and share intron/exon boundaries |
| SLP76 | SLNK, BLNK, SLP76, MIST | Yes | No | Yes | SLP76 contains a SAM domain |
| SOCS |
SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS6, SOCS7, CISH |
Yes | Yes | No | Different splice patterns |
| SRC |
SRC, FYN, LCK, FGR, YES, LYN, HCK, BLK |
No | No | Yes | Shares sequence similarity and similar domain organization to FRK |
| STAP | BKS, BRDG1 | Yes | Yes | Yes | Same domain organization as SH3BP2 and SH2B |
| STAT |
STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6 |
Yes | Yes | Yes | |
| SPT6 | SUPT6H | Yes | Yes | Yes | |
| SYK | ZAP70, SYK | Yes | Yes | Yes | |
| TEC | BMX, TEC, BTK, ITK, TXK | Yes | No | Yes | TXK lacks a PH and BTK domain |
| TNS | TNS1, TNS3, TENC1, TNS4 | Yes | No | Yes | TenC1 has a C1 and TNS1 has a PTPc domain |
| VAV | VAV1, VAV2, VAV3 | Yes | Yes | Yes |