Integrin alpha-5

Function

Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. ITGA5:ITGB1 acts as a receptor for fibronectin (FN1) and mediates R-G-D-dependent cell adhesion to FN1. ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling. ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling.

Classification

Family (Pfam)

PF01839 FG-GAP, PF08441 Integrin_A_Ig_1, PF20805 Integrin_A_Ig_2, PF20806 Integrin_A_Ig_3

InterPro

FG-GAP, Int_alpha_beta-p, Integrin_alpha, Integrin_alpha_C_CS, Integrin_alpha_Ig-like_1, Integrin_alpha_Ig-like_2, Integrin_alpha_Ig-like_3, Integrin_alpha_N, Integrin_dom_sf

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 13

• 3VI3 X-ray 2.90A
• 3VI4 X-ray 2.90A
• 4WJK X-ray 1.85A
• 4WK0 X-ray 1.78A
• 4WK2 X-ray 2.50A
• 4WK4 X-ray 2.50A
• 7NWL EM 3.10A
• 7NXD EM 4.60A
• 9B9J EM 2.60A
• 9B9K EM 2.70A
• 9CKV EM 3.19A
• 9DIA EM 2.97A
• … and 1 more

A predicted model is available from AlphaFold.

Gene Ontology · 39

• GO:0071062 alphav-beta3 integrin-vitronectin complex
• GO:0009986 cell surface
• GO:0031410 cytoplasmic vesicle
• GO:0005783 endoplasmic reticulum
• GO:0009897 external side of plasma membrane
• GO:0005925 focal adhesion
• GO:0098978 glutamatergic synapse
• GO:0005794 Golgi apparatus
• GO:0034674 integrin alpha5-beta1 complex
• GO:0008305 integrin complex
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0001726 ruffle
• GO:0005509 calcium ion binding
• GO:0005154 epidermal growth factor receptor binding
• GO:0005178 integrin binding
• GO:0005161 platelet-derived growth factor receptor binding
• GO:0038023 signaling receptor activity
• GO:0043184 vascular endothelial growth factor receptor 2 binding
• GO:0001618 virus receptor activity
• GO:0001525 angiogenesis
• GO:0023035 CD40 signaling pathway
• GO:0007155 cell adhesion
• GO:0033627 cell adhesion mediated by integrin
• GO:0098609 cell-cell adhesion
• GO:0007160 cell-matrix adhesion
• GO:0031589 cell-substrate adhesion
• GO:0035987 endodermal cell differentiation
• GO:0007565 female pregnancy
• GO:0034113 heterotypic cell-cell adhesion
• GO:0007229 integrin-mediated signaling pathway
• GO:2000811 negative regulation of anoikis
• GO:0030335 positive regulation of cell migration
• GO:0010811 positive regulation of cell-substrate adhesion
• GO:1903672 positive regulation of sprouting angiogenesis
• GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway
• GO:1900748 positive regulation of vascular endothelial growth factor signaling pathway
• GO:0014850 response to muscle activity
• GO:0035313 wound healing, spreading of epidermal cells

Drugs targeting this protein · 1

• ATN-161 antagonist

Related proteins · sequence + function similarity

• Integrin alpha-5 0.99
• Integrin alpha-IIb 0.97
• Integrin alpha-IIb 0.97
• Integrin alpha-5 0.96
• Integrin alpha-10 0.91
• Integrin alpha-7 0.91
• Integrin alpha-3 0.90
• Integrin alpha-7 0.90
• Integrin alpha-IIb 0.90
• Integrin alpha-3 0.89
• Integrin alpha-3 0.89
• Integrin alpha-3 0.89

Co-cited proteins · studied together in the literature

• Integrin beta-1 16 shared papers
• Insulin-like growth factor-binding protein 2 2 shared papers
• Proprotein convertase subtilisin/kexin type 5 1 shared papers
• Integrin alpha-V 11 shared papers
• Integrin beta-3 10 shared papers
• Integrin alpha-3 2 shared papers
• Minor capsid protein VP1 1 shared papers
• Integrin alpha-4 4 shared papers
• Insulin-like growth factor-binding protein 1 1 shared papers
• BLOC-2 complex member HPS5 1 shared papers
• Minor capsid protein VP1 1 shared papers
• Angiopoietin-2 1 shared papers

Literature · 37 cited papers

• The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand. Life. Sci Alliance · 2023
• Structural insights into integrin alpha5beta1 opening by fibronectin ligand. Sci. Adv. · 2021
• The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection. JACC Basic Transl. Sci. · 2021
• Characterization of ANGPT2 mutations associated with primary lymphedema. Sci. Transl. Med. · 2020
• Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling. J. Immunol. · 2019
• Direct binding to integrins and loss of disulfide linkage in interleukin-1beta (IL-1beta) are involved in the agonistic action of IL-1beta. J. Biol. Chem. · 2017
• Insulin-Like Growth Factor Binding Protein-2 Promotes Adhesion of Endothelial Progenitor Cells to Endothelial Cells via Integrin alpha5beta1. J. Mol. Neurosci. · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a newly identified binding site (site 2) in integrins alphavbeta3, alpha4beta1, and alpha5beta1. J. Biol. Chem. · 2015
• Roles of the putative integrin-binding motif of the human metapneumovirus fusion (f) protein in cell-cell fusion, viral infectivity, and pathogenesis. J. Virol. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Identification of novel integrin binding partners for calcium and integrin binding protein 1 (CIB1): structural and thermodynamic basis of CIB1 promiscuity. Biochemistry · 2013
• … and 25 more in the literature graph