In molecular biology, the forkhead-associated domain (FHA domain) is a phosphopeptide recognition domain found in many regulatory proteins.^[1] It displays specificity for phosphothreonine-containing epitopes but will also recognise phosphotyrosine with relatively high affinity. It spans approximately 80-100 amino acid residues folded into an 11-stranded beta sandwich, which sometimes contains small helical insertions between the loops connecting the strands.^[2]

To date, genes encoding FHA-containing proteins have been identified in eubacterial, eukaryotic and archaeal genomes. The domain is present in a diverse range of proteins, such as kinases, phosphatases, kinesins, transcription factors, RNA-binding proteins and metabolic enzymes which partake in many different cellular processes - DNA repair, signal transduction, vesicular transport and protein degradation are just a few examples.

The forkhead associated (FHA) domain of polynucleotide kinase phosphatase (PNKP) is necessary for the recruitment of PNKP to damage sites in DNA.^[3] PNKP is active in the repair of DNA damage by the processes of base excision repair, single-strand break repair and non-homologous end joining in the case of double strand breaks.^[3] In these activities PNKP acts both as a kinase and a phosphatase in the ligation of DNA ends. The kinase domain phosphorylates 5' hydroxyl ends, and the phosphatase domain removes phosphates from 3' ends. These activities, acting together, prepare single-strand breaks with damaged termini for ligation.