NEK7
Domain
Displays an autoinhibited conformation: Tyr-97 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9.
The NTE (N-terminal extension) motif is a structural component of the catalytic domain and thus contributes to activity.
Function
Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:19941817, PubMed:31409757). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:19941817, PubMed:26522158, PubMed:31409757). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953).
Post-translational modifications
Phosphorylation at Ser-195 required for its activation.
Sequence Similarities
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Tissue Specificity
Highly expressed in lung, muscle, testis, brain, heart, liver, leukocyte and spleen. Lower expression in ovary, prostate and kidney. No expression seen in small intestine.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Spindle pole
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Present at centrosome throughout the cell cycle (PubMed:17586473). Also detected at spindle midzone of the anaphase cells and eventually concentrates at the midbody (PubMed:17586473). Interaction with ANKS3 prevents its translocation to the nucleus (By similarity).
Alternative names
Serine/threonine-protein kinase Nek7, Never in mitosis A-related kinase 7, NimA-related protein kinase 7, NEK7