The immunoglobulin superfamily (IgSF) is a heterogenic group of proteins built on a common fold, called the Ig fold, which is a sandwich of two ßp sheets. Although members of the IgSF share a similar Ig fold, they differ in their tissue distribution, amino acid composition, and biological role.
In this paper we report an up-to-date compilation of the IgSF where all known members of the IgSF are classified on the basis of their common functional role (immune system, antibiotic proteins, enzymes, cytokine receptors, etc.) and their distribution in tissue (neural system, extracellular matrix, tumor marker, muscular proteins, etc.), or in species (vertebrates, invertebrates, bacteria, viruses, fungi, and plants). The members of the family can contain one or many Ig domains, comprising two basic types: the constant domain (C), with seven strands, and the variable domain (V), with eight, nine, or ten strands. The different overviews of the IgSF led to the definition of new domain subtypes, mainly concerning the C type, based on the distribution of strands within the two sheets.
The wide occurrence of the Ig fold and the much less conserved sequences could have developed from a common ancestral gene and/or from a convergent evolutionary process. Cell adhesion and pattern recognition seem to be the common feature running through the entire family.
Proteins families Immunoglobulin fold Domains Fibronectin type III Evolution Function Constant domains Variable domains
Bartl S, Baltimore D, Weissman IL (1994) Molecular evolution of the vertebrate immune system. Proc Natl Acad Sci USA 87:6934–6938Google Scholar
Bork P, Doolittle RF (1992) Proposed acquisition of an animal protein domain by bacteria. Proc Natl Acad Sci USA 89:8990–8994PubMedCrossRefGoogle Scholar
Bork P, Holm L, Sander C (1994) The immunoglobulin fold. Structural classification, sequence patterns and common core. J Mol Biol 242:309–320PubMedGoogle Scholar
Brunmendorf T, Rathjen F (1994) Cell adhesion molecules 1: Immunoglobulin Superfamily. Protein profile, 1, issue 9. Academic PressGoogle Scholar
Fukunaga R, Ishizaka-Ikeda E, Pan C-X, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10:2855–2865PubMedGoogle Scholar
Gerstein M, Altman RB (1995) Average core structures and variability measures for protein families: application to the immunoglobulins. J Mol Biol 251:161–175PubMedCrossRefGoogle Scholar
Jin DY, Li ZL, Jin Q, Hao YW, Hou YD (1989) Vaccinia virus hemagglutinin. A novel member of the immunoglobulin superfamily. J Exp Med 170:571–576PubMedCrossRefGoogle Scholar
Jones CH, Pinkner JS, Nicholes AV, Slonium LN, Abraham SN, Hultgren SJ (1993) FimC is a periplasmic PapD-like chaperone that directs assembly of type 1 pili in bacteria. Proc Natl Acad Sci USA 90:8397–8401PubMedCrossRefGoogle Scholar
Jones EY, Davis SJ, Williams AF, Harlos K, Stuart DI (1992) Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2. Nature 360:232–239PubMedCrossRefGoogle Scholar
Kasahara M, Vasquez M, Sato K, McKinney C, Flajnik MF (1992) Evolution of the major histocompatibility complex: isolation of class IIA cDNA clones from the cartilaginous fish. Proc Natl Acad Sci USA 89:6688–6692PubMedCrossRefGoogle Scholar
Kraulis P (1991) MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J Appl Cryst 24:946–950CrossRefGoogle Scholar
Kuma KI, Iwabe N, Miyata T (1991) The immunoglobulin superfamily. Curr Opin Struct Biol 1:384–393CrossRefGoogle Scholar
Lakey A, Labeit S, Gautel M, Ferguson C, Barlow DP, Leonard K, Bullard B. (1993) Kettin, a large modular protein in the Z-disc of insect muscles. EMBO J 12:2863–2871PubMedGoogle Scholar
Lindstrom-Dinnetz I, Sun S-C, Faye I (1995) Structure and expression of Hemolin, an insect member of the immunoglobulin superfamily. Eur J Biochem 230:920–925PubMedCrossRefGoogle Scholar
Little E, Bork P, Doolittle RF (1994) Tracing the spread of fibronectin type III domains in bacterial glycohydrolases. J Mol Evol 39:631- 643PubMedCrossRefGoogle Scholar
Price MG, Gomer RH (1993) Skelemin, a cytoskeletal M-disc periphery protein, contains motifs of adhesion/recognition and intermediate filament proteins. J Biol Chem 268:21800–21810PubMedGoogle Scholar
Symons JA, Alcami A, Smith GL (1995) Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity. Cell 81:551–560PubMedCrossRefGoogle Scholar
Thoreau E, Petridou B, Kelly PA, Djiane J, Mornon J-P (1991) Structural symmetry of the extracellular domain of the cytokine/growth hormone/prolactin receptor family and interferon receptors revealed by Hydrophobic Cluster Analysis. FEBS Lett 282:26- 31PubMedCrossRefGoogle Scholar
Williams AF, Barclay AN (1988) The immunoglobulin superfamily. Domains for cell surface recognition. Annu Rev Immunol 6:381- 405PubMedGoogle Scholar