12CA5 Fv-clasp fragment (green, cyan) with its antigen peptide, YPYDVPDYA (magenta), which is used as HA tag. Image created with PyMOL from PDB: 5XCS.
The HA-tag is a protein tag derived from the human influenza hemagglutinin (HA) protein, which allows the virus to target and enter host cells. An HA-tag is composed of a peptide derived from the HA-molecule corresponding to amino acids 98-106, which can be recognized and selectively bound by commercially available antibodies. This makes HA a powerful tool in molecular biology, commonly included in expression vectors and in the production of recombinant proteins.
[1] Like other epitope tags, HA-tag is small and generally does not alter the traits of proteins it is attached to.[2] As a result HA-tags are often used to identify protein-protein interactions or to detect protein expression, using Co-Immunoprecipitation or Western blot respectively.[3][4]
The HA-tag is not suitable for detection or purification of proteins from apoptotic cells since it is cleaved by Caspase-3 and / or Caspase-7 after its sequence DVPD, causing it to lose its immunoreactivity.[5] Labeling of endogenous proteins with HA-tag using CRISPR was recently accomplished in-vivo in differentiated neurons.[6]
Sequence
The DNA sequences for the HA-tag include: 5'-TAC-CCA-TAC-GAT-GTT-CCA-GAT-TAC-GCT-3' or 5'-TAT-CCA-TAT-GAT-GTT-CCA-GAT-TAT-GCT-3'. The resulting amino acid sequence is YPYDVPDYA (Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala).[7]
^Schembri L, Dalibart R, Tomasello F, Legembre P, Ichas F, De Giorgi F (February 2007). "The HA tag is cleaved and loses immunoreactivity during apoptosis". Nature Methods. 4 (2): 107–8. doi:10.1038/nmeth0207-107. PMID17264856. S2CID32173039.
