FLAG tag Created 2026-10-20 Updated 2026-11-05
The FLAG tag is an engineered epitope tag with the eight-residue sequence DYKDDDDK. Tag-specific antibodies permit detection or affinity capture of a fused protein. Its short length makes it convenient but does not guarantee neutrality: placement near a targeting sequence or functional interface can change behaviour. Comparing the tagged construct with an appropriate untagged or independently validated version tests whether it preserves the relevant function. [ref]
A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification by T. P. Hopp and others. Hopp and others, 1988, A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification
T. P. Hopp 2026-11-05
T. P. Hopp led the 1988 paper introducing the short peptide marker now called the FLAG tag. The engineered eight-residue sequence DYKDDDDK supplied an antibody-recognized handle for detecting and purifying recombinant proteins. Because the handle was shared, the same recognition reagent could be used with otherwise different target proteins.[ref]
A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification by T. P. Hopp and others. Abstract: eight-residue N-terminal tag, antibody detection and immunoaffinity purification
The experiment connects sequence design to a practical measurement problem: an arbitrary target need not already have its own suitable antibody. Tag accessibility and its effect on the target still matter in a new application; success for the proteins tested does not establish that every fusion is functionally unchanged.