Li J, Lee G I, Van Doren S R, Walker J C
Division of Biological Sciences and Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
J Cell Sci. 2000 Dec;113 Pt 23:4143-9. doi: 10.1242/jcs.113.23.4143.
The forkhead-associated (FHA) domain is a phosphopeptide-binding domain first identified in a group of forkhead transcription factors but is present in a wide variety of proteins from both prokaryotes and eukaryotes. In yeast and human, many proteins containing an FHA domain are found in the nucleus and involved in DNA repair, cell cycle arrest, or pre-mRNA processing. In plants, the FHA domain is part of a protein that is localized to the plasma membrane and participates in the regulation of receptor-like protein kinase signaling pathways. Recent studies show that a functional FHA domain consists of 120-140 amino acid residues, which is significantly larger than the sequence motif first described. Although FHA domains do not exhibit extensive sequence similarity, they share similar secondary and tertiary structures, featuring a sandwich of two anti-parallel (beta)-sheets. One intriguing finding is that FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine, distinguishing them from other well-studied phosphoprotein-binding domains. The diversity of proteins containing FHA domains and potential differences in binding specificities suggest the FHA domain is involved in coordinating diverse cellular processes.
叉头相关（FHA）结构域是一种磷酸肽结合结构域，最初在一组叉头转录因子中被鉴定出来，但在原核生物和真核生物的多种蛋白质中都存在。在酵母和人类中，许多含有FHA结构域的蛋白质存在于细胞核中，并参与DNA修复、细胞周期停滞或前体mRNA加工。在植物中，FHA结构域是一种定位于质膜的蛋白质的一部分，并参与类受体蛋白激酶信号通路的调控。最近的研究表明，一个功能性的FHA结构域由120 - 140个氨基酸残基组成，这比最初描述的序列基序要大得多。尽管FHA结构域没有表现出广泛的序列相似性，但它们具有相似的二级和三级结构，其特征是由两个反平行β折叠组成的三明治结构。一个有趣的发现是，FHA结构域可能结合磷酸苏氨酸、磷酸丝氨酸，有时还结合磷酸酪氨酸，这使它们与其他经过充分研究的磷蛋白结合结构域有所不同。含有FHA结构域的蛋白质的多样性以及结合特异性的潜在差异表明，FHA结构域参与协调多种细胞过程。
