Integrin beta, epidermal growth factor-like domain 1
IPR040622
Definition
This is the first EGF-like domain found in several integrin beta subunits. This domain lacks one disulphide (C2-C4) relative to the integrin EGF 2, 3, and 4 domains; this allows the C-terminal end of EGF1 to flex remarkably relative to its N-terminal end PMID:26936951. EGF-like domains in beta subunits contain three disulphide groups with the same connectivity as in other EGF domains. The disulphide bonds function as critical "locks" for integrin inactivity, with bond disruption enabling activation PMID:22308022. Each EGF-like domain contains three β strands, with the first two antiparallel strands (A and B) forming a major β sheet found in classical EGF domains. Strand C is hydrogen bonded to strand D, which is contributed in part by the consecutive domain, with strands C and D forming a minor β sheet-like conformation PMID:19704023. Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [[interpro:IPR033760]]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [[interpro:IPR002369]]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) [[cite:PMID:9009218], [cite:PMID:12388743]]. This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [[interpro:IPR040622]], [[interpro:IPR057073]], [interpro:IPR013111]]. Finally, this is followed by the β-ankle TM domain [[interpro:IPR012896]] and a cytoplasmic tail [[interpro:IPR014836]] PMID:28510180. 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.
5 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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