| Accession: | |
|---|---|
| Functional site class: | SPAK-OSR1 docking motif |
| Functional site description: | The Ste20-related proline alanine-rich kinase (SPAK) and oxidative stress response kinase (OSR1) are the only two mammalian serine-threonine kinases belonging to the germinal centre-like kinase subfamily VI. The CCT domain of SPAK/OSR1 proteins represents a novel protein fold called SPOC. The CCT domains of human SPAK-OSR1 are 79% identical at the sequence level and are also highly conserved in other metazoan organisms. The main described function of the CCT domain SPOC fold is to interact with a particular docking site called the RFxV motif in order to bind and phosphorylate the target proteins. The RFxV motif is also found in the upstream activating kinases WNK1 and WNK4 and so it is also used to dock these activating kinases to their SPAK/OSR1 substrates. |
| ELM Description: | The SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates by interacting with their RFxV motifs. The Conserved C-Terminal (CCT) domain of SPAK and OSR1 acts as a binding domain for this interaction. The primary pocket of the CCT domain forms a web of molecular interactions with the Arg, Phe and Val residues of the RFxV-containing peptide and mutation of any of the conserved residues prevents the interaction. Ile is allowed at the V position. Proline is not allowed at the X position due to the backbone contacts it makes in the beta augmentation with the edge beta strand of the CCT. The motif has so far only been found in the Metazoa. |
| Pattern: | RF[^P][IV]. |
| Pattern Probability: | 0.0000768 |
| Present in taxon: | Metazoa |
| Interaction Domain: |
OSR1_C (PF12202)
Oxidative-stress-responsive kinase 1 C terminal
(Stochiometry: 1 : 1)
PDB Structure: 2V3S
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