Integrin alpha-L

Function

Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is a receptor for F11R. Integrin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Acts as a platform at the immunological synapse to translate TCR engagement and density of the ITGAL ligand ICAM1 into graded adhesion. Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis (By similarity). Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. Integrins ITGAL:ITGB2 functions as a receptor of the neuron-specific adhesion molecule ICAM5 ensuring neuron cell-leukocyte adhesion. Integrin ITGAL/ITGB2 that functions as a signaling receptor of ICAM2, ensuring leukocyte cell-cell adhesion on resting cells.

Classification

Family (Pfam)

PF01839 FG-GAP, PF08441 Integrin_A_Ig_1, PF20805 Integrin_A_Ig_2, PF00357 Integrin_alpha, PF00092 VWA

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_N, Integrin_dom_sf, VWF_A, vWFA_dom_sf

Functional cluster

Immunoglobulin & Immune-Response Proteins

Experimental structures · PDB · 41

• 1CQP X-ray 2.60A
• 1DGQ NMR
• 1LFA X-ray 1.80A
• 1MJN X-ray 1.30A
• 1MQ8 X-ray 3.30A
• 1MQ9 X-ray 2.00A
• 1MQA X-ray 2.50A
• 1RD4 X-ray 2.40A
• 1T0P X-ray 1.66A
• 1XDD X-ray 2.20A
• 1XDG X-ray 2.10A
• 1XUO X-ray 1.80A
• … and 29 more

A predicted model is available from AlphaFold.

Gene Ontology · 28

• GO:0009986 cell surface
• GO:0070062 extracellular exosome
• GO:0034687 integrin alphaL-beta2 complex
• GO:0008305 integrin complex
• GO:0016020 membrane
• GO:0045121 membrane raft
• GO:0005886 plasma membrane
• GO:0035579 specific granule membrane
• GO:0050839 cell adhesion molecule binding
• GO:0030369 ICAM-3 receptor activity
• GO:0046872 metal ion binding
• GO:0044877 protein-containing complex binding
• GO:0038023 signaling receptor activity
• GO:0007155 cell adhesion
• GO:0033627 cell adhesion mediated by integrin
• GO:0098609 cell-cell adhesion
• GO:0033631 cell-cell adhesion mediated by integrin
• GO:0007160 cell-matrix adhesion
• GO:0007157 heterophilic cell-cell adhesion
• GO:0006954 inflammatory response
• GO:0007229 integrin-mediated signaling pathway
• GO:0007159 leukocyte cell-cell adhesion
• GO:0035683 memory T cell extravasation
• GO:0007158 neuron cell-cell adhesion
• GO:0006909 phagocytosis
• GO:0043113 receptor clustering
• GO:0007165 signal transduction
• GO:0002291 T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell

Drugs targeting this protein · 1

• LIFITEGRAST antagonist

Related proteins · sequence + function similarity

• Integrin alpha-L 0.99
• Integrin alpha-L 0.99
• Integrin alpha-D 0.96
• Integrin alpha-E 0.96
• Integrin alpha-D 0.96
• Integrin alpha-X 0.96
• Integrin alpha-D 0.95
• Integrin alpha-M 0.95
• Integrin alpha-E 0.95
• Integrin alpha-E 0.95
• Integrin alpha-X 0.95
• Integrin alpha-M 0.94

Co-cited proteins · studied together in the literature

• Integrin beta-2 10 shared papers
• Intercellular adhesion molecule 1 3 shared papers
• Intercellular adhesion molecule 3 2 shared papers
• Intercellular adhesion molecule 4 1 shared papers
• Junctional adhesion molecule A 2 shared papers
• CD226 antigen 1 shared papers
• Intercellular adhesion molecule 5 1 shared papers
• ORF7a protein 1 shared papers
• Intercellular adhesion molecule 2 1 shared papers
• Integrin alpha-L 1 shared papers
• Thrombomodulin 1 shared papers
• Integrin alpha-M 1 shared papers

Literature · 28 cited papers

• LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity. Nat. Commun. · 2024
• Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor. Mol. Cell · 2017
• LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin. Biochem. Biophys. Res. Commun. · 2016
• Leukocyte integrin alphaLbeta2 headpiece structures: The alphaI domain, the pocket for the internal ligand, and concerted movements of its loops. Proc. Natl. Acad. Sci. U.S.A. · 2016
• Novel role of ICAM3 and LFA-1 in the clearance of apoptotic neutrophils by human macrophages. Apoptosis · 2013
• Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat. Biotechnol. · 2009
• SARS-CoV accessory protein 7a directly interacts with human LFA-1. Biol. Chem. · 2007
• Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms. J. Cell Biol. · 2005
• An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin alphaLbeta2. Proc. Natl. Acad. Sci. U.S.A. · 2005
• Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1 (CD226). Int. Immunol. · 2005
• The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
• The functional interaction of the beta 2 integrin lymphocyte function-associated antigen-1 with junctional adhesion molecule-A is mediated by the I domain. J. Immunol. · 2004
• … and 16 more in the literature graph