CDB15:0000799 ICAM4 — ITGAV

Experimentally validated in Human, Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Intercellular adhesion molecule-4 binds alpha(4)beta(1) and alpha(V)-family integrins through novel integrin-binding mechanisms.

Blood, 2001; PubMed, Homo sapiens ICAM4 — Homo sapiens ITGAV

ABSTRACT: The LW blood group glycoprotein, ICAM-4, is a member of the intercellular adhesion molecule (ICAM) family expressed in erythroid cells. To begin to address the function of this molecule, ligands for ICAM-4 on hemopoietic and nonhemopoietic cell lines were identified. Peptide inhibition studies suggest that adhesion of cell lines to an ICAM-4-Fc construct is mediated by an LDV-inhibitable integrin on hemopoietic cells and an RGD-inhibitable integrin on nonhemopoietic cells. Antibody inhibition studies identified the hemopoietic integrin as alpha(4)beta(1.) Antibody inhibition studies on alpha(4)beta(1)-negative, nonhemopoietic cell lines suggested that adhesion of these cells is mediated by alpha(V) integrins (notably alpha(V)beta(1) and alpha(V)beta(5)). The structure of ICAM-4 modeled on the crystal structure of ICAM-2 was used to identify surface-exposed amino acid residues for site-directed mutagenesis. Neither an unusual LETS nor an LDV motif in the first domain of ICAM-4 was critical for integrin binding. ICAM-4 is the first ICAM family member shown to be a ligand for integrins other than those of the beta(2) family, and the data suggest that ICAM-4 has a novel integrin-binding site(s). These findings suggest a role for ICAM-4 in normal erythropoiesis and may also be relevant to the adhesive interactions of sickle cells.

Integrin receptor specificity for human red cell ICAM-4 ligand. Critical residues for alphaIIbeta3 binding.

European journal of biochemistry, 2004; PubMed, Mus Musculus Icam4 — Homo sapiens ITGAV

ABSTRACT: The red cell intercellular adhesion molecule-4 (ICAM-4) binds to different members of the integrin receptor families. To better define the ICAM-4 integrin receptor specificity, cell transfectants individually expressing various integrins were used to demonstrate that alphaLbeta2, alphaMbeta2, and alphaIIbbeta3 (activated) bind specifically and dose dependently to the recombinant ICAM-4-Fc protein. We also show that cell surface ICAM-4 interacts with the cell surface alphaVbeta3 integrin. In addition, using a alpha4beta1 cell transfectant and beta2 integrin-deficient LAD cells, we show here that ICAM-4 failed to interact with alpha4beta1 even after alpha4beta1 activation by phorbol ester or with the monoclonal antibody TS2/16 (+ Mn2+). ICAM-4 amino acids that are critical for alphaIIbbeta3 and alphaVbeta3 interaction were identified by domain deletion analysis, site-directed mutagenesis and synthetic peptide inhibition. Our results provide evidence that the beta3 integrin binding sites encompass the first and second Ig-like domains of ICAM-4. However, while the alphaIIbbeta3 contact site comprises the ABED face of domain D1 with an extension in the C'-E loop of domain D2, the alphaVbeta3 contact site comprises residues on both faces of D1 and in the C'-E loop of D2. These data, together with our previous results, demonstrate that different integrins bind to different but partly overlapping sites on ICAM-4, and that ICAM-4 may accommodate multiple integrin receptors present on leukocytes, platelets and endothelial cells.

Basic Information on ICAM4

Ligand Name: intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)

Other Symbols: LW, CD242

Ligand Location: secreted based on perplexity, uniprot, cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: ICAM4

GeneCards: ICAM4

HGNC Gene Group: Ig-like cell adhesion molecule family, Blood group antigens, CD molecules, Immunoglobulin superfamily domain containing

Functional Annotations for ICAM4

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for ICAM4

ICAM4 — ITGA2B ・ ICAM4 — ITGA4 ・ ICAM4 — ITGAL ・ ICAM4 — ITGAM ・ ICAM4 — ITGB1 ・ ICAM4 — ITGB2 ・ ICAM4 — ITGB3 ・ ICAM4 — ITGAX ・ ICAM4 — ITGB5

Basic Information on ITGAV

Receptor Name: integrin subunit alpha V

Other Symbols: VNRA, MSK8, VTNR, CD51

Receptor Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: ITGAV

GeneCards: ITGAV

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGAV

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for ITGAV

ADAM15 — ITGAV ・ ADAM9 — ITGAV ・ ANGPTL3 — ITGAV ・ AZGP1 — ITGAV ・ COL1A1 — ITGAV ・ COL4A3 — ITGAV ・ CCN1 — ITGAV ・ EDIL3 — ITGAV ・ FBN1 — ITGAV ・ FGA — ITGAV ・ FGB — ITGAV ・ FGG — ITGAV ・ FN1 — ITGAV ・ IBSP — ITGAV ・ L1CAM — ITGAV ・ LAMA4 — ITGAV ・ MFGE8 — ITGAV ・ NID1 — ITGAV ・ SPP1 — ITGAV ・ TGFB1 — ITGAV ・ TNC — ITGAV ・ VTN — ITGAV ・ CX3CL1 — ITGAV ・ CXCL12 — ITGAV ・ FNDC5 — ITGAV ・ PLA2G2A — ITGAV ・ ADAM23 — ITGAV ・ AGRN — ITGAV ・ ANGPT2 — ITGAV ・ CCN3 — ITGAV ・ CD40LG — ITGAV ・ COL18A1 — ITGAV ・ COMP — ITGAV ・ DMP1 — ITGAV ・ EGFL7 — ITGAV ・ FBLN2 — ITGAV ・ FCER2 — ITGAV ・ FGF1 — ITGAV ・ FGF2 — ITGAV ・ HMGB1 — ITGAV ・ IGF1 — ITGAV ・ IGF2 — ITGAV ・ IL1B — ITGAV ・ NRG1 — ITGAV ・ PECAM1 — ITGAV ・ PLAUR — ITGAV ・ POSTN — ITGAV ・ PTN — ITGAV ・ TGFB3 — ITGAV ・ THBS1 — ITGAV ・ THY1 — ITGAV ・ VWF — ITGAV