Integrins beta, I-EGF domain, conserved site
IPR057243
Definition
This entry represents a conserved region of the I-EGF domain that includes five of the conserved cysteines. The C terminus of the extracellular region of all the integrin beta chains has four cysteine-rich tandem repeats of forty amino acids, which are variants of the EGF-like domain, termed integrin- or I-EGF domains. The I-EGF domain is a small globular domain mainly composed by loops with a small anti-parallel β-sheet constituted of two β-strands (see [PDBe:1L3Y]). The structure is stabilised by four disulfide bonds between the first and fifth, second and fourth, third and sixth, and seventh and eighth Cys residues. Three disulfide bonds are shared with classical EGF-like domains. The disulfide unique to I-EGF domains links the N terminus to the turn between the two β-strands. Compared to classical EGF-like modules with three disulfide bonds, the I-EGF module is less elongated, with a nosecone-like shape. The anti parallel sheet between the two β-strands is shortened because four highly conserved residues among classical EGF-like modules are deleted in I-EGF modules. I-EGF repeats in the integrin beta subunit stalk region relay activation signals to the ligand-binding headpiece [[cite:PMID:1918072], [cite:PMID:11896403]]. Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways [[cite:PMID:12297042], [cite:PMID:12361595]]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal. Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits PMID:12234368. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans PMID:14689578. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule PMID:2467745. Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.
8 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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