CSNK1A1 Antibody

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Product Specs

Form
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
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Synonyms
Casein kinase 1 alpha 1 antibody; Casein kinase I isoform alpha antibody; CK1 antibody; CK1A antibody; CKI alpha antibody; CKI-alpha antibody; CKIa antibody; Clock regulator kinase antibody; Csnk1a1 antibody; Down regulated in lung cancer antibody; HLCDGP1 antibody; KC1A_HUMAN antibody; PRO2975 antibody
Target Names
Uniprot No.

Target Background

Function
Casein kinases are characterized by their preference for acidic proteins, such as caseins, as substrates. They can phosphorylate a wide array of proteins. Casein kinase 1 alpha (CK1α) participates in Wnt signaling, phosphorylating CTNNB1 at Ser-45. It may also phosphorylate PER1 and PER2. CK1α could potentially play a role in chromosome segregation during mitosis, keratin cytoskeleton disassembly, and ultimately, epithelial cell migration.
Gene References Into Functions
  1. Research suggests that CK1α similarly destabilizes FOXO4 in RAS-mutant cells through phosphorylation at serines 265/268. PMID: 28945225
  2. Data indicate that CK1α RNA levels could serve as a prognostic marker for colorectal cancer (CRC). PMID: 29409464
  3. CK1α, a cellular kinase, is crucial for IAV HA-induced degradation of both IFNGR1 and IFNAR1. PMID: 29343571
  4. Casein kinase 1 phosphorylates the SQSTM1 S349 residue when harmful proteins accumulate under HSF1 stress. PMID: 27846364
  5. Maintenance of progenitors necessitates collaboration between PRMT1 and CSNK1a1 to sustain proliferation gene expression and suppress premature differentiation driven by GRHL3. PMID: 28943242
  6. These data suggest that CK1α plays a dominant and non-redundant role in melanoma cells. PMID: 27488834
  7. Disrupting CK1α function in myeloma cells resulted in decreased Mdm2, increased p53 and p21, and reduced expression of beta-catenin and AKT. PMID: 28099937
  8. CK1δ enhances EPO secretion from liver cancer cells under hypoxia by modifying HIF-2α and promoting its nuclear accumulation. PMID: 27686097
  9. CKIα-mediated NS5A S235 phosphorylation is essential for HCV replication. CaMKII gamma and delta may have negative roles in the HCV life cycle. PMID: 27875595
  10. Interactome analyses revealed that the Jade-1S mutant, unable to be phosphorylated by CK1α, exhibits increased binding affinity to proteins involved in chromatin remodeling, histone deacetylation, transcriptional repression, and ribosome biogenesis. PMID: 26919559
  11. This study investigates how the structural dynamics and conformational changes of two CK1 isoforms are synchronized in the carcinogenic pathway. PMID: 26788877
  12. NIFK is required for lung cancer progression through RUNX1-dependent CK1α repression, which activates TCF4/beta-catenin signaling in metastasis and Ki-67-dependent regulation in cell proliferation. PMID: 26984280
  13. The study describes the identification of a novel, tumor-specific missense mutation in the active site of casein kinase 1 alpha (CSNK1A1) using activity-based proteomics. PMID: 27031502
  14. This research characterizes the frequency and potential clinical impact of CSNK1A1 mutations in myelodysplastic syndrome (MDS) and acute myeloid leukemia following MDS in a large patient cohort. PMID: 25792355
  15. The dynamical and conformational properties of three CK1 isoforms are explored through molecular dynamics (MD) simulations. PMID: 25665722
  16. Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering through differential interaction with ARHGEF7. PMID: 25500533
  17. Casein kinase 1α is a key negative regulator of oncogenic RAS-induced autophagy. Depletion or pharmacologic inhibition of CK1α enhanced autophagic flux in oncogenic RAS-driven human fibroblasts and multiple cancer cell lines. PMID: 25798617
  18. CSNK1alpha1 plays a role in mediating malignant plasma cell survival. PMID: 24962017
  19. Casein kinase 1α specifically phosphorylates Jade-1 at an unprimed SLS phosphorylation site. PMID: 25100726
  20. Degradation of Tiam1 by casein kinase 1 and the SCFbetaTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling. PMID: 25124033
  21. Data indicate that protein S phosphorylation by casein kinase 1 (CK1) and casein kinase 2 (CK2) increased activated proten C cofactor activity. PMID: 23580615
  22. The substrate interacting residues in ck1α have been identified using the structural model of kinase - substrate peptide. The PKR interacting NS5A 1b residues have also been predicted. PMID: 23148689
  23. DNA damage activates p53, in part, by disrupting CK1α-MDMX interaction and reducing MDMX-p53 binding affinity. PMID: 23028042
  24. Casein kinase 1α (CK1α) was identified as a direct target of miR-155 control, which enhanced beta-catenin signaling and cyclin D1 expression, promoting tumor cell growth. PMID: 22350414
  25. Just four genes, G3BP2, SCARB2, CSNK1A1, and SPRR2B, can classify patients as having lymph node metastasis negative or positive, with 80.0% accuracy. PMID: 21985131
  26. mTOR cooperates with CK1α and betaTrCP to create an auto-amplification loop promoting its own full activation. PMID: 22017877
  27. Researchers characterized the role of CKIα in the clock mechanism and found that CKIα-mediated phosphorylation stimulated degradation of a clock protein PER1, similar to the function of CKIδ. PMID: 21179498
  28. Findings indicate that the nuclear form of CK1α in humans, CK1αLS, plays a critical role in vascular cell proliferation, cellular activation, and hydrogen peroxide-mediated mitogenic signal transduction. PMID: 20696773
  29. Casein kinase 1 functions as both the penultimate and ultimate kinase in regulating Cdc25A destruction. PMID: 20348946
  30. Biochemical and cellular characteristics of the four splice variants of protein kinase CK1α from zebrafish (Danio rerio) are presented. PMID: 12210746
  31. CK1α can promote cell survival by interfering with RXR agonist-induced apoptosis. PMID: 15131121
  32. CK1α-mediated phosphorylation modulates the mRNA binding ability of hnRNP-C. PMID: 15687492
  33. NFAT1, a transcription factor associated with breast cancer metastasis, is activated by Wnt-5a through a Ca2+ signaling pathway in human breast epithelial cells, which was simultaneously counteracted by a Wnt-5a-induced Yes/Cdc42 signaling pathway. PMID: 16880514
  34. The alpha isoform of casein kinase I was identified as the cellular kinase critical for the formation of hepatitis C virus (HCV) NS5A-p58; this research demonstrates the effects of this kinase on NS5A hyperphosphorylation and HCV replication. PMID: 16943283
  35. CK1αLS and hnRNP-C represent conserved components of a vertebrate-specific H(2)O(2)-responsive nuclear signaling pathway. PMID: 17626781
  36. Studies suggest that CK1α is another kinase that regulates RIP1 function in NF-kappaB activation. PMID: 18067272
  37. Following DNA damage, PML facilitates Thr18 phosphorylation by recruiting p53 and CK1 into PML nuclear bodies, thereby protecting p53 from inhibition by Mdm2, leading to p53 activation. PMID: 18246126
  38. Ser-155 and Ser-158 play crucial roles in the nucleocytoplasmic trafficking of OREBP/TonEBP, and CK1 plays a significant role in regulating this process. PMID: 18411282
  39. This research demonstrates that inhibiting CK1 activates RhoB and promotes RhoB-dependent actin fiber formation and EGF-R level. PMID: 18590726
  40. CK1 plays a role as the Ser20 site kinase for p53 in DNA virus-infected cells. PMID: 18669630
  41. Phosphorylation of parkin by casein kinase I and cdk5 decreases parkin solubility, leading to its aggregation and inactivation. PMID: 19050041
  42. The 'activated B-cell-like' subtype of diffuse large B-cell lymphoma cells required CK1α for constitutive NF-kappaB activity, indicating that CK1α functions as a conditionally essential malignancy gene. PMID: 19118383
  43. Casein Kinase 1 phosphorylates serine 56 of yellow fever virus methyltransferase. PMID: 19185594
  44. Data show that Wnt-5a stimulation of breast epithelial cells leads to increased cell-cell adhesion, and that Wnt-5a/casein kinase Iα (CKIα)-specific phosphorylation of beta-catenin leads to increased complex formation of beta-catenin/E-cadherin. PMID: 19244247
  45. CK1α plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability. PMID: 19759023
  46. Results suggest a role for mammalian and parasite casein kinase 1α in regulating IFNAR1 stability and type I IFN signaling. PMID: 19805514

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Database Links

HGNC: 2451

OMIM: 600505

KEGG: hsa:1452

UniGene: Hs.529862

Protein Families
Protein kinase superfamily, CK1 Ser/Thr protein kinase family, Casein kinase I subfamily
Subcellular Location
Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Chromosome, centromere, kinetochore. Nucleus speckle. Cytoplasm, cytoskeleton, cilium basal body. Cytoplasm, cytoskeleton, spindle.

Q&A

What experimental strategies validate CSNK1A1 antibody specificity in western blotting?

Validating antibody specificity requires a multi-step approach:

  • Knockout/Knockdown Controls: Compare wild-type (WT) and CSNK1A1 knockout (KO) or siRNA-treated cell lysates. A study screening ten commercial antibodies demonstrated that only 40% showed complete signal loss in KO lysates, underscoring the necessity of genetic controls .

  • Band Pattern Analysis: CSNK1A1 migrates at ~37 kDa. Researchers should verify absence of non-specific bands at 55 kDa (common cross-reactivity with CSNK1D/E isoforms) .

  • Orthogonal Validation: Combine western blot with immunoprecipitation-mass spectrometry to confirm target identity, as implemented in standardized antibody characterization pipelines .

Key Validation Data from Recent Studies

Antibody CloneKO ValidationOff-Target BandsRecommended Dilution
CAB9308CompleteNone observed1:500 - 1:2000
55192-1-APPartial55 kDa band1:1000
ab196684Not testedUncharacterized1:50 (IHC)

How does CSNK1A1 regulate Wnt/β-catenin signaling, and which antibody applications best capture this interaction?

CSNK1A1 phosphorylates β-catenin at Ser45, initiating its degradation via the β-TrCP ubiquitin ligase complex . To study this:

  • Co-Immunoprecipitation (Co-IP): Use antibodies validated for IP (e.g., CAB9308 ) to pull down CSNK1A1-β-catenin complexes from Wnt3a-stimulated cells.

  • Subcellular Localization: High-performance IF antibodies (e.g., those showing >5-fold signal reduction in KD cells ) reveal cytoplasmic-to-nuclear β-catenin shifts upon CSNK1A1 inhibition.

  • Phospho-Specific Assays: Pair CSNK1A1 antibodies with phospho-β-catenin (Ser45) reagents to quantify kinase activity dynamics.

What cell lines are optimal for CSNK1A1 functional studies?

Selection criteria include:

  • Endogenous Expression: HCT 116 colorectal cancer cells show highest CSNK1A1 levels (DepMap TPM >8.5) .

  • Knockout Viability: Use inducible KO systems, as constitutive CSNK1A1 knockout is lethal in many lines .

  • Pathway Activity: SW480 (APC mutant) cells provide high β-catenin background to assess CSNK1A1-mediated degradation .

How should researchers resolve contradictory CSNK1A1 localization data between immunofluorescence and biochemical fractionation?

Contradictions often arise from:

  • Fixation Artifacts: Methanol fixation may leak soluble CSNK1A1; compare with paraformaldehyde results .

  • Antibody Epitope Accessibility: Screen multiple clones (e.g., N-terminal vs. C-terminal epitopes) across fixation/permeabilization conditions .

  • Fractionation Validation: Verify cytoplasmic/nuclear separation using Lamin B1 and GAPDH controls. A 2024 study found only 60% of antibodies reproduced localization across methods .

What multiplex assay designs improve CSNK1A1 pathway analysis?

Innovative approaches include:

  • Mosaic Culture IF: Label WT and CSNK1A1 KD HCT 116 cells with CellTracker Green/Deep Red, then co-culture and stain in situ to control for batch effects .

  • Phosphoproteomics Integration: Combine IP-validated antibodies (Table 1) with TiO2 phosphopeptide enrichment to map CSNK1A1 substrate networks.

  • Live-Cell Biosensors: Use CSNK1A1 antibody-validated KO lines to calibrate FRET reporters for real-time β-catenin degradation kinetics.

Multiplex Workflow Validation Metrics

ParameterAcceptable RangeAntibody-Dependent Variability
Co-IP Efficiency>20% enrichment±15% across clones
IF Signal Specificity>5:1 (WT/KO)3.8:1 - 8.2:1
Cross-Reactivity<5% with CSNK1DUp to 37% in some lots

Which experimental parameters most significantly impact CSNK1A1 antibody performance in immunohistochemistry?

Critical factors identified in multi-laboratory studies:

  • Epitope Stability: Prolonged formalin fixation (>48 hrs) masks conformational epitopes; optimize retrieval pH (citrate pH6 vs. Tris-EDTA pH9) .

  • Phosphorylation State: Commercial antibodies show up to 40% reduced affinity for autophosphorylated CSNK1A1 . Include lambda phosphatase-treated controls.

  • Cell Cycle Synchronization: CSNK1A1 levels vary 2.3-fold between G1/S phases; standardize harvest times .

How can researchers address CSNK1A1 antibody lot-to-lot variability in longitudinal studies?

Mitigation strategies:

  • Batch Testing: Pre-screen new lots against reference samples (WT/KO lysates, peptide arrays).

  • Epitope Mapping: Select antibodies targeting linear epitopes (e.g., CAB9308 ) rather than conformational.

  • Public Data Utilization: Cross-reference with characterization databases (YCharOS, Antibody Registry) for performance benchmarks .

Western Blot Troubleshooting Guide

IssueSolutionSupporting Data
Multiple bandsPre-absorb with 1 μg/mL immunogen peptide Reduces non-specific bands by 78%
Weak signalBoil samples in 1% SDS pre-loadingImproves epitope accessibility 3-fold
Inconsistent KO dataVerify >90% knockdown via qPCRCorrelation r=0.92 with WB

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