Contents

ICAM3

Mammalian protein found in Homo sapiens

ICAM3
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1T0P
Identifiers
Aliases	ICAM3, CD50, CDW50, ICAM-R, intercellular adhesion molecule 3
External IDs	OMIM: 146631; HomoloGene: 88479; GeneCards: ICAM3; OMA:ICAM3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 10,333,776 bp[1] End 10,339,661 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood granulocyte monocyte bone marrow cells trabecular bone periodontal fiber spleen lymph node right lobe of liver appendix n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function integrin binding signaling receptor binding protein binding Cellular component integral component of membrane plasma membrane integral component of plasma membrane extracellular exosome membrane Biological process cell adhesion extracellular matrix organization stimulatory C-type lectin receptor signaling pathway regulation of immune response phagocytosis cell-cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3385 n/a Ensembl ENSG00000076662 n/a UniProt P32942 n/a RefSeq (mRNA) NM_002162 NM_001320605 NM_001320606 NM_001320608 NM_001395374 NM_001395375 NM_001395376 n/a RefSeq (protein) NP_001307534 NP_001307535 NP_001307537 NP_002153 n/a Location (UCSC) Chr 19: 10.33 – 10.34 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Intercellular adhesion molecule 3 (ICAM3) also known as CD50 (Cluster of Differentiation 50), is a protein that in humans is encoded by the ICAM3 gene.^[3] The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system.^[4][5] ICAM3 mediates adhesion between cells by binding to specific integrin receptors.^[6] It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation.^[7][8] ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.^[6][9][10]

Protein structure[edit]

ICAM3 is a 110–160 kDa protein that belongs to the intercellular adhesion molecule (ICAM) family.^[4] Like the other proteins in this family, ICAM3 is a type I transmembrane glycoprotein and consists in part of a hydrophobic transmembrane domain and a short domain that extends into the cytoplasm.^[11] ICAM3 also contains five extracellular immunoglobulin domains.^[11]

Function[edit]

ICAM3 is found on the surface of leukocytes, and the ICAM3 gene is constitutively expressed in these cells.^[4] Interactions between ICAM3 and specific integrin receptors facilitate adhesion between cells.^[6]

Dendritic and T cell binding[edit]

ICAM3 has an important function in the immune cell response, as it helps facilitate initial interactions between T cells and dendritic cells.^[12] Resting T cells show high levels of ICAM3 expression.^[12] ICAM3 on these T cells can bind to DC-SIGN, a transmembrane receptor present on dendritic cells, creating temporary contact between resting T cells and dendritic cells.^[7][8] This adhesion allows the T cell receptor (TCR) to interact with major histocompatibility complex (MHC) molecules on the surface of the dendritic cell, which, upon binding between the TCR, the MHC, and the peptide coupled to the MHC, facilitates T cell activation.^[7][8][12]

Apoptosis[edit]

ICAM3 plays a role in apoptotic cell clearance by promoting the movement of macrophages, which ingest and break down unhealthy cells via phagocytosis, to cells undergoing apoptosis.^[9] Apoptotic cells can release extracellular vesicles containing ICAM3, which acts as a chemoattractant to phagocytes such as macrophages, directing them toward apoptotic cells.^[6][13] Apoptotic cells also contain altered ICAM3 proteins on their surface.^[10] These altered proteins allow macrophages to specifically target and bind apoptotic cells.^[10] This process is believed to involve binding between ICAM3 and CD14 receptors, which are a type of cell surface receptor expressed on macrophages and other phagocytes.^[6][10]

Mast cells[edit]

ICAM3 is also found on mast cells, another type of leukocyte.^[5] Mast cells taken from human lungs and the HMC-1 line, a human mast cell line, both showed expression of ICAM3.^[5] ICAM3 helps mediate the adhesion of mast cells to the extracellular matrix.^[5]

Interactions[edit]

Dendritic and T cell binding[edit]

Binding between ICAM3 and DC-SIGN, which takes place during initial interactions between T cells and dendritic cells, occurs with high affinity.^[7][12][14] This binding process is also calcium-dependent.^[7][12][14]

Apoptosis[edit]

CD14, a receptor expressed on the surface of phagocytes, can also bind ICAM3.^[6][10] Interactions between CD14 and altered ICAM3 molecules on apoptotic cells are believed to help promote phagocytosis of apoptotic cells.^[6][10]

Integrins[edit]

ICAM3 is a known ligand for LFA-1, an integrin expressed by leukocytes.^[12] To facilitate binding, the I domain of LFA-1 interacts with the ICAM3 protein’s first immunoglobulin domain.^[12] ICAM3 also binds the integrin αDβ2.^[11]

Additional interactions[edit]

ICAM3 has been shown to interact with activated ERM proteins, including ezrin (EZR) and moesin, in T cells.^[15]

See also[edit]

• Cluster of differentiation

References[edit]

Further reading[edit]

External links[edit]

• ICAM3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.