Summary of integrin evolution across a broad range of species: αI domain specialization, as seen in humans, is a vertebrate invention.

<p>Individual domains having the same fold class as integrin component domains (i.e. β propeller, immunoglobulin fold, epidermal growth factor fold, vWFA) are observed already in prokaryotes but the earliest diverging sets of identifiable integrin subunits have been observed in the choanozoan <i>C. owczarzaki</i>, a single-cell eukaryote. The number of α and β subunits expands with increasing organismal complexity with 18 α and 8 β subunits forming up to 24 heterodimers in humans. Integrins undergo considerable functional diversification with the introduction of the αI domain in some α subunits. Tunicates like <i>C. intestinalis</i> and <i>H. roretzi</i> are the earliest diverging organisms where integrins with αI domains have been identified, but they are not direct vertebrate orthologues as they form a distinct clade. αI domain containing fragments can be detected in the lamprey <i>P. marinus</i> and possibly the hagfish <i>E. burgeri</i>; both are extant representatives of the first vertebrates. The lamprey fragments share characteristic features in common with the human collagen-binding αI domain group and they bind different mammalian collagens at MIDAS; four shark sequences are orthologues of the corresponding human α subunits, three collagen binding and one from the leukocyte clade, and duplicate isoforms are observed in observed in bony fish e.g. <i>D. rerio</i>, <i>C. carpio</i> and <i>O. niloticus</i>.