Nuclear factor of activated T-cells 5 (NFAT5) is a member of the nuclear factors of activated T cells (NFAT) of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. NFAT5, regulated by DDX5/DDX17, plays a role in the migratory capacity of breast cancer cells []. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Five transcript variants encoding three different isoforms have been identified for this gene [].NFAT proteins appear to be regulated primarily at the level of their subcellular localisation []. They are found exclusively in the cytoplasm of resting T cells, and consist of 2 components: a pre-existing cytoplasmic component that translocates into the nucleus on calcium mobilisation, and an inducible nuclear component comprising members of the activating protein-1 (AP-1) family of transcription factors. In response to antigen receptor signalling, the calcium-regulated phosphatase calcineurin acts directly to dephosphorylate NFAT proteins, causing their rapid translocation from the cytoplasm to the nucleus, where they cooperatively bind their target.
The immunoglobulin (Ig) like fold, which consists of a β-sandwich of seven or more strands in two sheets with a greek-key topology, is one of the most common protein modules found in animals. Many different unrelated proteins share an Ig-like fold, which is often involved in interactions, commonly with other Ig-like domains via their β-sheets []. Of these, the "early"set (E set) domains are possibly related to the immunoglobulin () and/or fibronectin type III () Ig-like protein superfamilies. Ig-like E set domains include:C-terminal domain of certain transcription factors, such as the pro-inflammatory transcription factor NF-kappaB, and the T-cell transcription factors NFAT1 and NFAT5 [].Ig-like domains of sugar-utilising enzymes, such as galactose oxidase (C-terminal domain), sialidase (linker domain), and maltogenic amylase (N-terminal domain).C-terminal domain of arthropod haemocyanin, where many loops are inserted into the fold. These proteins act as dioxygen-transporting proteins.C-terminal domain of class II viral fusion proteins. These envelope glycoproteins are responsible for membrane fusion with target cells during viral invasion.Cytomegaloviral US (unique short) proteins. These type I membrane proteins help suppress the host immune response by modulating surface expression of MHC class I molecules [].Molybdenium-containing oxidoreductase-like dimerisation domain found in enzymes such as sulphite reductase.ML domains found in cholesterol-binding epididymal secretory protein E1, and in a major house-dust mite allergen; ML domains are implicated in lipid recognition, particularly the recognition of pathogen-related products.Rho-GDI-like signalling proteins, which regulate the activity of small G proteins [].Cytoplasmic domain of inward rectifier potassium channels such as Girk1 and Kirbac1.1. These channels act as regulators of excitability in eukaryotic cells.N-terminal domain of transglutaminases, including coagulation factor XIII; many loops are inserted into the fold in these proteins. These proteins act to catalyse the cross-linking of various protein substrates [].Filamin repeat rod domain found in proteins such as the F-actin cross-linking gelation factor ABP-120. These proteins interact with a variety of cellular proteins, acting as signalling scaffolds [].Arrestin family of proteins, which contain a tandem repeat of two elaborated Ig-like domains contacting each other head-to-head. These proteins are key to the redirection of GPCR signals to alternative pathways [].C-terminal domain of arginine-specific cysteine proteases, such as Gingipain-R, which act as major virulence factors of Porphyromonas gingivalis (Bacteroides gingivalis).Copper-resistance proteins, such as CopC, which act as copper-trafficking proteins [].Cellulosomal scaffoldin proteins, such as CipC module x2.1. These proteins act as scaffolding proteins of cellulosomes, which contain cellulose-degrading enzymes [].Quinohaemoprotein amine dehydrogenases (A chain), which contain a tandem repeat of two Ig-like domains. These proteins function in electron transfer reactions.Internalin Ig-like domains, which are truncated and fused to a leucine-rich repeat domain. These proteins are required for host cell invasion of Listeria species.
