forkhead associated (FHA) domain found in Saccharomyces cerevisiae fork head protein homolog 1 (FKH1), 2 (FKH2) and similar proteins
This family includes FKH1 and FKH2, as well as pre-rRNA-processing protein FHL1. FKH1 and FKH2 are forkhead transcription factors that regulate the expression of the CLB2 cluster of genes during the G2/M phase of the mitotic cell cycle. The CLB2 cluster of genes includes mitotic regulators such as CLB1, CLB2, CDC5 and CDC20, as well as SWI5 and ACE2. FKH1 and FKH2 are involved in HMRa silencing. They associate with the coding regions of active genes and influence, in opposing ways, transcriptional elongation and termination, and coordinate early transcription elongation and pre-mRNA processing. Both FKH1 and FKH2 play a role as regulators of lifespan in collaboration with the anaphase-promoting complex (APC), likely through combined regulation of stress response, genomic stability, and cell cycle regulation. They also function in controlling yeast cell morphology by preventing pseudohyphal growth and act as rate-limiting replication origin activators via their interaction with the origin recognition complex (ORC). FHL1 is a forkhead protein that controls the pre-rRNA processing machinery in conjunction with IFH1. It might act as a transcriptional regulator of genes specifically involved in that process. IFH1 convert FHL1 from a repressor to an activator. This family also includes AtFHA1 and AtFHA2, which may play a role in the control of plant organ development. AtFHA2 is specifically involved in the regulation of stamen development. The FHA domain is a small phosphopeptide recognition module.
Feature 1:putative phosphopeptide binding site [polypeptide binding site]
Evidence:
Comment:based on structures of other FHA domains with bound phosphopeptide
Comment:GR at the C terminus of strand beta3, SRxH just preceding beta5, and motif SxNG in the beta6-beta7 turn indicate a canonical mode of pThr recognition.
Comment:Conserved residues are involved in binding directly to the ligand backbone and phosphate group. Non-conserved residues may determine binding specificity.
Jiyao W et al.(2023). "The conserved domain database in 2023.",