InterPro: IPR014756 Immunoglobulin E-set

The immunoglobulin (Ig) like fold, which consists of a beta-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 beta-sheets [1]. Of these, the "early" set (E set) domains are possibly related to the immunoglobulin (IPR007110) and/or fibronectin type III (IPR003961) 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 [2].
• 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 [3].
• 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 [4].
• 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 [5].
• 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 [6].
• 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 [7].
• 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 [8].
• Cellulosomal scaffoldin proteins, such as CipC module x2.1. These proteins act as scaffolding proteins of cellulosomes, which contain cellulose-degrading enzymes [9].
• 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.