Table 1. Summary of nucleotide, divalent cation and inhibitor binding by pseudokinases.
The G-loop was defined as degraded if two of three positions do not conform to the sequence [GSA]xGxx[GSA] where x is any amino acid.
| (a) Class 1 (devoid of nucleotide- or cation-binding) | ||||||
|---|---|---|---|---|---|---|
|
| ||||||
| Pseudokinase | Degraded G-loop | VAIK motif lysine residue present | HRD motif aspartic acid residue present | DFG motif aspartic acid residue present | DAP or VI16832 binding | |
| Ror1 | No | + | + | + | − | |
| BubR1 | Yes | + (TFVK)* | + | + (DNA)* | − | |
| RYK | No | + | + | + (DNA)* | − (DAP) | |
| RYK TFVK>VAVK | No | + | + | + | + | |
| CASK | No | + | + | − | − | |
| PTK7/CCK4 | No | + | + | − | − | |
| SgK223 | Yes | + | + | − | − | |
| SgK495/STK40 | Yes | + | + | − | − | |
| TRB2 | Yes | + | + | − | − | |
| TYK2(JH2) | No | + | − | + | + | |
| IRAK3 | No | + | − | + | + | |
| GCN2 | Yes | − | − | + | − | |
| VRK3 | Yes | + | − | − | − | |
| BPK1 | Yes | + | − | − | − | |
| NRBP1 | Yes | − | − | − | − | |
| SCYL1 | Yes | − | − | − | − | |
| MviN | Yes | − | − | − | − | |
|
| ||||||
| (b) Class 2 (nucleotide-binding) | ||||||
|
| ||||||
| Pseudokinase | Degraded G-loop | VAIK motif lysine residue present | HRD motif aspartic acid residue present | DFG motif aspartic acid residue present | DAP or VI16832 binding | |
|
| ||||||
| ULK4 | No | − | + (FCD)* | − | − | |
| MLKL | Yes | + | − | − | − | |
| EphB6 | No | − (VTVR)* | − | − | + | |
| STRADα | No | − | − | − | − | |
|
| ||||||
| (c) Class 3 (cation-binding) | ||||||
|
| ||||||
| Pseudokinase | Degraded G-loop | VAIK motif lysine residue present | HRD motif aspartic acid residue present | DFG motif aspartic acid residue present | DAP or VI16832 binding | |
|
| ||||||
| SgK269 | Yes | + | + | − | − | |
| ROP2 | Yes | − | + | − | − | |
|
| ||||||
| (d) Class 4 (nucleotide- and cation-binding) | ||||||
|
| ||||||
| Pseudokinase | Degraded G-loop | VAIK motif lysine residue present | HRD motif aspartic acid residue present | DFG motif aspartic acid residue present | DAP or VI16832 binding | Catalytic activity? |
|
| ||||||
| JAK1(JH2) | No | + | − | + | + (VI16832) | No [70] |
| JAK2(JH2) | No | + | − | + (DVK)* | + | Yes [20,53] |
| ILK | Yes | + | − | + | − | No [27,41] |
| HER3/ErbB3 | No | + | − | + | − | Yes [19] |
| SgK071 | No | + | − | + | − | Unknown |
| CRN | No | + | − | + | + | No [37] |
| ROP5B I | No | + | − | + | − (VI16832) | No [29] |
| IRAK2 | No | + | − | − (EFG)* | + (VI16832) | Unlikely [66,67] |
| TARK1 | Yes | + | − | − | + | No [38] |
| EphB6 R813D | No | − | − | + | + | Unknown |
*
Motif sequence noted due to similarity/difference from conventional motif