CSNK2A1 Human, His
Description
Overview of CSNK2A1 Human, His
CSNK2A1 Human, His refers to a recombinant human casein kinase 2 alpha 1 (CK2α1) protein fused with a polyhistidine (His) tag. This protein is a catalytic subunit of the constitutively active serine/threonine-protein kinase CK2 complex, which regulates diverse cellular processes such as cell cycle progression, apoptosis, and circadian rhythm . The His tag facilitates purification and detection in experimental workflows .
Protein Architecture
-
Quaternary Structure: CK2α1 forms a tetrameric holoenzyme with two catalytic subunits (α/α') and two regulatory β-subunits .
-
Catalytic Domain: Residues 1–335 encompass the kinase domain, critical for ATP binding and substrate phosphorylation .
-
Post-Translational Modifications: Autophosphorylation occurs at Ser362, enhancing stability and activity .
Crystal Structures
Biological Processes
-
Cell Cycle Regulation: Phosphorylates CDC25B and CHEK1, modulating checkpoint control .
-
Neuromuscular Homeostasis: Conditional knockout in mice causes age-dependent muscle weakness, impaired autophagy, and fragmented neuromuscular junctions .
-
Ciliary Stability: Maintains primary cilia structure by opposing TTBK2 activity; mutations destabilize cilia tips and dysregulate Sonic Hedgehog signaling .
Key Substrates
| Substrate | Phosphorylation Site | Functional Impact |
|---|---|---|
| PTEN | Ser370/Ser385 | Modulates tumor suppression |
| RELA | Ser536 | Enhances NF-κB transcriptional activity |
| APC | Multiple sites | Regulates Wnt/β-catenin signaling |
Okur-Chung Neurodevelopmental Syndrome (OCNDS)
-
Genetic Cause: De novo missense mutations (e.g., Arg47Gly, Lys198Arg) in CSNK2A1 .
-
Clinical Features: Intellectual disability, autistic traits, cortical malformations, and dysmorphic facial features .
-
Mechanism: Mutations disrupt kinase activity or substrate binding, leading to ciliary instability and aberrant signaling .
Cancer
Recombinant Protein Applications
-
Source: Produced in E. coli with ≥90% purity (Thermo Fisher, Cat# PV3992) .
-
Storage: Stable at -80°C for six months; avoid repeated freeze-thaw cycles .
Murine Knockout Phenotypes
| Model | Phenotype |
|---|---|
| Csnk2a1 conditional KO | Reduced grip strength, mitochondrial dysfunction, increased autophagy |
| Csnk2a1 OCNDS variants | Ciliary elongation, actin cytoskeleton defects |
Inhibitors
| Compound | IC₅₀ (CK2α) | Mechanism |
|---|---|---|
| TBBt | 2.56 µM | Halogenated triazolo-pyridine; competitive ATP binding |
| DMAT | 0.14 µM | Selective CK2 inhibition; anti-proliferative effects |
Mutation Hotspots in OCNDS
| Mutation (Nucleotide) | Protein Change | Clinical Impact | Source |
|---|---|---|---|
| c.593A>G | Lys198Arg | Impaired kinase-substrate interaction | |
| c.139C>G | Arg47Gly | Disrupted ATP binding | |
| c.468T>A | Asp156Glu | Altered regulatory domain |
Future Directions
Current research focuses on:
Product Specs
Product Science Overview
The CK2 complex is a tetramer composed of two catalytic alpha subunits (CSNK2A1 and CSNK2A2) and two regulatory beta subunits (CSNK2B). The alpha subunits are responsible for the catalytic activity, while the beta subunits undergo autophosphorylation . The human recombinant form of CSNK2A1 is often tagged with a His-tag to facilitate purification and detection in research applications .
CSNK2A1 is involved in numerous cellular processes, including:
- Cell Cycle Control: It regulates the progression of the cell cycle by phosphorylating various substrates involved in cell division .
- Apoptosis: CSNK2A1 plays a role in programmed cell death, influencing the balance between cell survival and apoptosis .
- Circadian Rhythm: It is implicated in the regulation of circadian rhythms, affecting the body’s internal clock .
- Transcription and Gene Expression: CSNK2A1 is involved in the regulation of transcription and gene expression by phosphorylating transcription factors and other proteins involved in these processes .
The human recombinant form of CSNK2A1, tagged with a His-tag, is widely used in research to study its function and interactions. This recombinant protein is produced in various expression systems, such as baculovirus or E. coli, and is purified using chromatographic techniques . It is used in kinase assays, structural studies, and drug discovery efforts to develop inhibitors targeting CK2 activity .
