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|Functional site class:||Integrin binding sites|
|Functional site description:||Integrins are cell surface receptors responsible for cell migration, cell to extracellular matrix adhesion, and cell to cell adhesion. Integrins are composed of one alpha and one beta subunits. NGR motif is an inactive precursor in fibronectin and fibrillin-1 that undergoes deamidation and forms active isoDGR motif capable of binding RGD-binding pocket of several integrins including alphaVbeta3 and alpha5beta1 integrins. Binding of isoDGR motif to RGD-binding site in integrins inhibits endothelial cells adhesion (17015452). RGD-binding site is a composite binding site in integrins made of alpha and beta subunits. Integrins are used by viruses to gain entry into the host. Example is adeno-associated type II virus which binds to integrin alpha5beta1 via NGR motif to gain viral entry into the host cell (16940508). NGR motif-containing peptides coupled to certain drugs are specific against CD13-positive tumour angiogenic vessels.|
|ELMs:||LIG_IBS_1 LIG_Integrin_isoDGR_1 LIG_RGD|
|Description:|| NGR (asparagine-glycine-arginine) is a tripeptide present in fibronectin (FINC_HUMAN), fibrillin-1 (FBN1_HUMAN), and adeno-associated virus 2 protein capsid (CAPSD_AAV2S). Asparagine deamidation of NGR motif yields isoDGR (isoaspartic acid-glycine-arginine) motif. Deamidation is a non-enzymatic process that involves formation of succinimide intermediate and subsequent formation of isoDGR by hydrolysis. IsoDGR motif is able to interact with integrins by recognition of RGD-binding site of several integrins including αVβ3 integrin. RGD composite binding site is formed by both alpha and beta subunits of integrins and is located on the extracellular side of plasma membrane. IsoDGR binds to RGD-binding site in inverted orientation compared to proteins that contain RGD motif (18480047).
CisoDGRC is a cyclic peptide that competes with RGD-containing peptides for binding to αVβ3 integrins (17015452). CisoDGRC binding to RGD-binding pocket inhibits endothelial cell adhesion, proliferation, and tumour growth. Both ligands have similar binding affinity for αVβ3 integrin. CisoDGRC binds to the following integrins with decrease in affinity: αVβ3, α5β1, αVβ6, αVβ5, αVβ8. Linear isoDGR (GisoDGRG) binds to αVβ6, αVβ3, α5β1, αVβ5, and αVβ8. Cyclic isoDGR binds with 10-100-fold increased affinity to αVβ3 compared to other integrins. Acetylation of either linear or cyclic isoDGR increases the affinity for integrins accompanied by loss of specificity. Peptide linearization (replacing flanking glycines with cysteines) is associated with 100-fold loss of αVβ3 binding affinity and specificity. Hence, flanking residues of NGR motif affect affinity and specificity for integrin binding (20064928).
|Pattern:||NGR (Probability: 0.0001597)|
|Present in taxons:||Bos taurus Canis lupus familiaris Danio rerio Gallus gallus Homo sapiens Metazoa Pan troglodytes Rattus norvegicus Sus scrofa Xenopus laevis|
Integrins are transmembrane receptors responsible primarily for cell migration and extracellular matrix adhesion. Integrins are heterodimers, composed of one alpha, and one beta subunit. They function through bidirectional signalling. There are 18 alpha and 8 beta subunits in the integrin family that assemble into 24 heterodimers. alpha subunits determine integrin ligand specificity whereas beta subunits are connected to the cytoskeleton. alpha and beta subunits are held by non-covalent interactions. Integrins are able to bind a variety of ligands including cell surface adhesion proteins and extracellular matrix proteins. Integrin signalling involves assembly of receptor-ligand complexes on extracellular side of plasma membrane. Integrin proteins are present only in metazoa with no integrins found in fungi, plants, or prokaryotes. The structure of integrin includes extracellular domain which contains ligand binging sites, plasma membrane regions, and short cytoplasmic domains (19693543, 21421922).
(click table headers for sorting)
|FINC_HUMAN||367||369||PCVLPFTYNGRTFYSCTTEG||true positive||---||Homo sapiens (Human)|
|FINC_HUMAN||501||503||MMRCTCVGNGRGEWTCIAYS||true positive||---||Homo sapiens (Human)|
|FINC_HUMAN||1432||1434||YVVSIVALNGREESPLLIGQ||true positive||---||Homo sapiens (Human)|
|FINC_MOUSE||264||266||LLQCVCTGNGRGEWKCERHA||true positive||---||Mus musculus (House mouse)|
|FINC_MOUSE||501||503||MMRCTCVGNGRGEWACIPYS||true positive||---||Mus musculus (House mouse)|
|FBN1_HUMAN||2304||2306||QTKPGICENGRCLNTRGSYT||true positive||---||Homo sapiens (Human)|
|FINC_HUMAN||263||265||LLQCICTGNGRGEWKCERHT||true positive||---||Homo sapiens (Human)|
|CAPSD_AAV2S||511||513||TGATKYHLNGRDSLVNPGPA||true positive||---||Adeno-associated virus 2 Srivastava/1982|