Cellular Analysis

Cellular Analysis

SNAP- and CLIP-tag protein labeling systems enable the specific, covalent attachment of virtually any molecule to a protein of interest. There are two steps to using this system: cloning and expression of the protein of interest as a SNAP-tag® fusion, and labeling of the fusion with the SNAP-tag substrate of choice. The SNAP-tag is a small protein based on human O6-alkylguanine-DNA-alkyltransferase (hAGT), a DNA repair protein. SNAP-tag substrates are dyes, fluorophores, biotin, or beads conjugated to guanine or chloropyrimidine leaving groups via a benzyl linker. In the labeling reaction, the substituted benzyl group of the substrate is covalently attached to the SNAP-tag. CLIP-tag™ is a modified version of SNAP-tag, engineered to react with benzylcytosine rather than benzylguanine derivatives. When used in conjunction with SNAP-tag, CLIP-tag enables the orthogonal and complementary labeling of two proteins simultaneously in the same cells. 

SNAP-tag® is a registered trademark of New England Biolabs, Inc.
CLIP-tag™ is a trademark of New England Biolabs, Inc.

Cellular Analysis includes these subcategories:

Starter Kits
SNAP-tag® Substrates
CLIP-tag™ Substrates
ACP/MCP-tag Substrates
Blocking Agents
Cloning Vectors & Control Plasmids
Biotin/Vista Labels
Building Blocks

    Publications related to Cellular Analysis:

  1. Eckhardt, M. et al. (2011). A SNAP-tagged detivative of HIV-1 - A versatile tool to study virus-cell interactions PLoS One . 6:e22007. DOI: 10.137/journal. P One .0022007
  2. Hoskins, A. et al. (2011). Ordered and dynamic assembly of single spliceoseoms Science . 331, 1289.
  3. Nicolle O. et al. (2010). Development of SNAP-tag-mediated live cell labeling as an alternative to GFP in Porphyromonas gingivalis FEMS Immunol. Med. Microbiol.  . 59, 357-363. PubMedID: 20482622
  4. Ruggiu A. A. et al. (2010). Fura-2FF-based calcium indicator for protein labeling Org. Biomol. Chem. . 8, 3398-3401.
  5. Campos, C. et al. (2010). Labeling cell structures and tracking cell lineage in zebrafish using SNAP-Tag Dev. Dynamics . 240, PubMedID: 820-827
  6. Alvarez-Curto J. et al. (2010). Ligand regulation of the quaternary organization of cell surface M3 muscarinic acetylcholine receptors analyzed by fluorescence resonance energy transfer (FRET) imaging and homogenous time-resolved FRET J. Biol. Chem. . 285, 23318-23330.
  7. Ciruela F. et al. (2010). Lighting up multiprotein complexes: lessons from GPCR oligomerization Trends Biotechnol . 28, 407-415.
  8. Kamiya M. and Johnsson K. (2010). Localizable and Highly Sensitive Calcium Indicator Based on a BODIPY Fluorophore Anal. Chem. . 82, 6472-6479.
  9. Rhee S. G. et al. (2010). Methods for detection and measurement of hydrogen peroxide inside and outside of cells Mol. Cells . 29, 539-549.
  10. Srikun, D. et al. (2010). Organelle-targetable fluorescent probes for imaging hydrogen peroxide in living cells via SNAP-tag protein labeling  J. Am. Chem. Soc. . 132, 4455-4465.
  11. Maurel D. et al. (2010). Photoactivatable and photoconvertible fluorescent probes for protein labeling ACS Chem. Biol. Asap .
  12. Kampmeier, F. et al. (2010). Rapid optical imaging of EGF receptor expression with a single-chain antibody SNAP-tag fusion protein Eur. J. Med. Mol. Imaging . DOI: 10.007/S00259-010-1482-5
  13. Hein B. et al. (2010). Stimulated emission depletion nanoscopy of living cells using SNAP-Tag fusion proteins Biophys. J.  . 98, 158-163.
  14. Dellagiacoma, C. et al. (2010). Targeted photoswitchable probe for nanoscopy of biological structures ChemBioChem . DOI: 10.1002/Cbic.201000189
  15. Geissbuehler M. et al. (2010). Triplet imaging of oxygen consumption during the contraction of a single smooth muscle cell Biophys. J. . 98, 339-349.
  16. Engin S. et al. (2010). Benzylguanine Thiol self-assembled monolayers for the immobilization of SNAP-tag proteins on microcontact-printed surface structures Langmuir . ASAP,
  17. Zelman-Femiak, M. et al. (2010). Covalent quantum dot receptor linkage via the acyl carrier protein for single-molecule tracking, internalization, and trafficking studies BioTechniques . 49, 2.
  18. Waichman S. et al. (2010). Functional Immobilization and Patterning of Proteins by an Enzymatic Transfer Reaction Anal. Chem. . 82, 1478-1485.
  19. Mosiewicz, K. A. et al. (2010). Phosphopantetheinyl Transferase-Catalyzed Formation of Bioactive Hydrogels for Tissue Engineering J. Am. Chem. Soc. . 132, 5972-5974.
  20. Hill Z. B. (2009). A chemical genetic method for generating bivalent inhibitors of protein kinases J. Am. Chem. Soc. . 131, 6686-6688.
  21. Ahier A. et al. (2009). A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids PLoS One . 4, e5651.
  22. Stein V. and Hollfeder F. (2009). An efficient method to assemble linear DNA templates for in vitro screening and selection systems Nuc. Acids Res . 37, e122/1-e122/9.
  23. Sletten E. and Bertozzi C. (2009). Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality Angew. Chem. Int. Ed. . 48, 6974-6998.
  24. Carroll C.W. et al. (2009). Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N Nat. Cell Biol. . 11, 896-902.
  25. Foltz D.R. et al. (2009). Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP Cell . 137, 472-84.
  26. Donovan C. et al. (2009). Characterization and subcellular localization of bacterial flotillin homologue Microbiology . 155, 1786-1799.
  27. Keppler A. et al. (2009). Chromophore-assisted laser inactivation of α- and γ-tubulin SNAP-tag fusion proteins inside living cells ACS Chem. Biol. . 4, 127-138.
  28. Chattopadhaya S. et al. (2009). Expanding the chemical Biologist's tool kit: chemical labelling strategies and its applications Curr. Med. Chem.  . 16, 4527-4543.
  29. Cornish, V. W. (2009). Fluorescence in living systems: applications in chemical biology Wiley Encyc. of Chem. Biol. . 2, 28-38.
  30. Degorce F. et al. (2009). HTRF: A technology tailored for drug discovery - a review of theoretical aspects and recent applications Curr. Chem. Genomics . 3, 22-32.
  31. Samoshkin A. et al. (2009). Human condensin function is essential for centromeric chromatin assembly and proper sister kinetochore orientation PLoS One . 4, e6831.
  32. Böhme I and Beck-Sickinger A. G. (2009). Illuminating the life of GPCRs Cell Commun. Signal . 7, 16.
  33. Bannwarth et. al. (2009). Indo-1 Derivatives for local calcium sensing JACS Chemical Biology . 4, 179-190.
  34. Milenkovic L. et al. (2009). Lateral transport of smoothened from the plasma membrane to the membrane of the cilium J. Cell Biol. . 187, 365-374.
  35. Farr G. A. et al. (2009). Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells J. Cell Biol. . 186, 269-282.
  36. Tivari R. and Parang K. (2009). Protein conjugates of SH3-domain ligands and ATP- competitive inhibitors as bivalent inhibitors of protein kinases ChemBioChem. . 10, 2445 - 2448.
  37. Brun M.A. et al. (2009). Semisynthetic fluorescent sensor proteins based on self-labeling protein tags J. Am. Chem. Soc. . 131, 5873-5784.
  38. Kapmeier F. et al. (2009). Site-Specific, covalent labeling of recombinant antibody fragments via fusion to an engineered version of 6-O-alkylguanine DNA alkyltransferase Bioconjug Chem. . 23-Apr,
  39. Uano Y. and Matsuzaki K. (2009). Tag-probe labeling methods for live-cell imaging of membrane proteins Biochim. Biophys. Acta. . 1788, 2124-2131.
  40. Johnsson K. (2009). Visualizing biochemical activities in living cells Nat Chem Biol . 5, 63-65.
  41. Neugart F. et al. (2009). Detection of ligand-induced CNTF receptor dimers in living cells by fluorescence cross correlation spectroscopy Biochim. Biophys. Acta.  . 1788, 1890-1900.
  42. Eggeling C. et al. (2009). Direct observation of the nanoscale dynamics of membrane lipids in a living cell Nature . 457, 1159-1163.
  43. Gralle M. et al. (2009). Neuroprotective secreted amyloid precursor protein acts by disrupting amyloid precursor protein dimers J. Biol. Chem. . 284, 15016-15025.
  44. Gautier A. et al. (2009). Selective cross-linking of interacting proteins using self-labeling tags J. Am. Chem. Soc. . 131, 17954-17962.
  45. Chidley C. et al. (2008). A designed protein for the specific and covalent heteroconjugation of biomolecules Bioconj. Chem. . 19, 1753-1756.
  46. Gautier A. et al. (2008). AGT/SNAP-Tag: A versatile tag for covalent protein labeling from probes and tags to study biomolecular function Ed. Edited by Miller, L. W. . 89-107.
  47. Banala J. et al. (2008). Caged substrates for protein labeling and immobilization Chembiochem . 4,
  48. Maurel D. et al. (2008). Cell-surface protein-protein interaction analysis with time-resolved FRET and SNAP-tag technologies: application to GPCR oligomerization Nature Methods . 5, 561-7.
  49. Adams D. G. et al. (2008). Cellular Ser/Thr-kinase assays using generic peptide substrates Curr. Chem. Gen. . 1, 54-64.
  50. Fururta, K. et al. (2008). Diffusion and directed movement: in vitro motile properties of fission yeast kinesin-14 Plk1 J. Biol. Chem.  . 283, 36465-36473.
  51. Erhardt, S. et al. (2008). Genome-wide analysis reveals a cell cycle-dependent mechanism controling centromere propagation J. Cell Biol.. 183, 805-818.
  52. Howland S.W. et al. (2008). Inducing efficient cross-priming using antigen-coated yeast particles J. Immunother. . 31, 607-19.
  53. Howland S.W. et al. (2008). Inducing efficient cross-priming using antigen-coated yeast particles J. Immunother.. 31, 607-19.
  54. Southwell, A.L. et al. (2008). Intrabodies binding the proline-rich domains of mutant huntingtin increase its turnover and reduce neurotoxicity J. Neurosci. . 28, 9013-20.
  55. Mao S. et al. (2008). Optical lock-in detection of FRET using synthetic and genetically encoded optical switches Biophys. J. . 94, 4515-24.
  56. Tomat, E. et al. (2008). Organelle-specific zinc detection using zinpyr-labeled fusion proteins in live cells J. Am. Chem. Soc. . 130,
  57. Lin M.Z. and Wang L. (2008). Selective labeling of proteins with chemical probes in living cells Physiology . 23, 131-141.
  58. McMurray, M.A. and Thorner, J. (2008). Septin stability and recycling during dynamic structural transitions in cell division and development Current Biology . 18, 1203-1208.
  59. Johnson K. (2008). SNAP-tag Technologies: Novel tools to study protein function NEB Expressions . 3.3, 1-3.
  60. Generosi J. et al. (2008). AMPA receptor imaging by infrared scanning near-field optical microscopy Physica Status Solidi C: Current Topics in Solid State Physics . 5, 2641-2644.
  61. Gautier A. et al. (2008). An engineered protein tag for multiprotein labeling in living cells Chemistry & Biology . 15, 128-136.
  62. Sunbul M. et al. (2008). Enzyme catalyzed site-specific protein labeling and cell imaging with quantum dots Chem. Comm. . 5927-5929.
  63. Generosi J. et al. (2008). Photobleaching-free infrared near-field microscopy localizes molecules in neurons J. App. Phys. . 104, 106102-1/3.
  64. Schulz C. and Köhn M. (2008). Simultaneous protein tagging in two colors Chemistry & Biology . 15,
  65. Kropf M. et al. (2008). Subunit-specific surface mobility of differentially labeled AMPA receptor subunits Eur. J. Cell Biol. . 87, 763-778.
  66. Iversen L. et al. (2008). Templated protein assembly on micro-contact-printed surface patterns. Use of the SNAP-tag protein functionality  Langumuir. May 17,
  67. Mottram L. F. et al. (2007). A Concise Synthesis of the Pennsylvania green fluorophore and labeling of intracellular targets with O6-Benzylguanine Derivatives  Org. Lett. . 9, 3741-3744.
  68. Stein, V. et al. (2007). A covalent chemical genotype-phenotype linkage for in vitro protein evolution ChemBioChem. . 8, 2191-4.
  69. Stenoien D. L. et al. (2007). Cellular trafficking of phospholamban and formation of functional sarcoplasmic reticulum during myocyte differentiation Am. J. Physiol. Cell Physiol.  . 292, C2084-C2094.
  70. O'Hare H.M. et al. (2007). Chemical probes shed light on protein function Curr. Opin. Struct. Biol. . 17, 488-94.
  71. Johnsson N. and Johnsson K. (2007). Chemical tools for biomolecular imaging ACS Chem. Biol. . 2, 31-38.
  72. Pick H. et al. (2007). Distribution plasticity of the human estrogen receptor alpha in live cells: distinct imaging of consecutively expressed receptors J. Mol. Biol. . 14, 1213-1223.
  73. Lemercier, G. et al. (2007). Inducing and sensing protein-protein interactions in living cells by selective cross-linking Angew Chem. Int. Ed . 4281-4284.
  74. Jansen L. et al (2007). Propagation of centromeric chromatin requires exit from mitosis  J. of Cell Bio. . 176, 795-805.
  75. Böhme. et al. (2007). Tracking of human Y receptors in living cells- A fluorescence approach Peptides. 28, 226-234.
  76. Zhou Z. et al. (2007). Genetically encoded short peptide tags for orthogonal protein labeling by Sfp and AcpS phosphopantetheinyl transferases ACS Chemical Biology . 2, 337-346.
  77. Liu E and Bruner S. D. (2007). Rational manipulation of carrier-domain geometry in nonribosomal peptide synthetases ChemBioChem. . 8, 617 - 621.
  78. Gronemeyer T. et al. (2006). Adding value to fusion proteins through covalent labeling Curr. Opin. Biotechn. . 16,
  79. Gronemeyer T. et al. (2006). Directed evolution of O6-alkylguanine-DNA alkyltransferase for applications in protein labeling Prot. Eng. Des. Sel. . 19, 309-16.
  80. Tirat A. et al. (2006). Evaluation of two novel tag-based labeling technologies for site-specific modification of proteins Int. J. Biol. Macromol.. 39, 66-76.
  81. Heinis C. et al. (2006). Evolving the substrate specificity of O6 alkylguanine DNA alkyltransferase through loop insertion for applications in molecular imaging ACS Chem Biol. . 1, 575-584.
  82. Krayl M. et al. (2006). Fluorescence-mediated analysis of mitochondrial preprotein import in vitro Anal. Biochem.  . 335, 81-9.
  83. Keppler A. et al. (2006). Fluorophores for live cell imaging of AGT fusion proteins across the visible spectrum BioTechniques . 41, 167-75.
  84. Meyer B.H. et al. (2006). Covalent labeling of cell-surface proteins for in vivo FRET studies FEBS Letters . 580, 1654-1658.
  85. Meyer B.H. et al. (2006). FRET imaging reveals that functional neurokinin-1 receptors are monomeric and reside in membrane microdomains of live cells Proc. Natl. Acad. Sci. USA . 103, 2138-43.
  86. Prummer M. et al. (2006). Post-translational covalent labeling reveals heterogeneous mobility of individual G protein-coupled receptors in living cells ChemBioChem . 7, 908-911.
  87. Sielaff I. et al. (2006). Protein function microarrays based on self-immobilizing and self-labeling fusion proteins  ChemBioChem . 7, 194-202.
  88. Jongsma M.A., Litjens R. H. (2006). Self-assembling protein arrays on DNA chips by auto-labeling fusion proteins with a single DNA address  Proteomics . 6, 2650-2655.
  89. Jacquier V. et al. (2006). Visualizing receptor trafficking in living PNAS . 103, 14325-14330.
  90. Juillerat A. et al. (2005). Engineering substrate specificity of O6-alkylguanine-DNA alkyltransferase for specific protein labeling in living cells ChemBioChem . 6, 1263-1269. PubMedID: 15934048
  91. Johnsson N. et al. (2005). Protein chemistry on the surface of living cells Chembiochem. . 6, 47-52.
  92. Regoes A. et al. (2005). SNAP-tag mediated live cell labeling as an alternative to GFP in anaerobic organisms BioTechniques . 39, 809-812. PubMedID: 16382896
  93. Kufer S.K. et al. (2005). Covalent immobilization of recombinant fusion proteins with hAGT for single molecule force spectroscopy Eur. Biophys. J . 35, 72-78.
  94. Yin J. et al. (2005). Labeling proteins with small molecules by site-specific posttranslational modification J Am Chem Soc. 126, 7754-7755.
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  • Simultaneous dual protein labeling inside live cells
  • Protein localization and translocation
  • Pulse-chase experiments
  • Receptor internalization studies
  • Selective cell surface labeling
  • Protein pull-down assays
  • Protein detection in SDS-PAGE
  • Flow cytometry
  • High throughput binding assays in microtiter plates
  • Biosensor interaction experiments
  • FRET-based binding assays
  • Single molecule labeling
  • Super-resolution microscopy


  • Clone and express once, then use with a variety of substrates
  • Non-toxic to living cells
  • Wide selection of fluorescent substrates
  • Highly specific covalent labeling
  • Simultaneous dual labeling

Protein Labeling with SNAP-tag and CLIP-tag

The SNAP- (gold) or CLIP-tag (purple) is fused to the protein of interest (blue). Labeling occurs through covalent attachment to the tag, releasing either a guanine or a cytosine moiety.

SNAP-tag®, CLIP-tag™ and ACP/MCP-tag Substrate Selection Chart

NEB offers a large selection of fluorescent labels (substrates) for SNAP-, CLIP-, ACP- and MCP-tag fusion proteins.