Intercellular adhesion molecule/vascular cell adhesion molecule, N-terminal (IPR003987)

Short name: ICAM_VCAM_N

Overlapping homologous superfamilies

Domain relationships



Intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1) are part of the immunoglobulin superfamily. They are important in inflammation, immune responses and in intracellular signalling events [PMID: 9151947]. The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They are known to bind to leucocyte integrins CD11/CD18 during inflammation and in immune responses. In addition, ICAMs may exist in soluble forms in human plasma, due to activation and proteolysis mechanisms at cell surfaces.

ICAM-1 (CD54) contains five Ig-like domains. It is expressed on leucocytes, endothelial and epithelial cells, and is upregulated in response to bacterial invasion. The protein is a ligand for lymphocyte-function associated (LFA) antigens and also a receptor for CD11a,b/CD18, fibrinogen, human rhinovirus and Plasmodium falciparum-infected erythrocytes. ICAM-1 binding sites for CD11a/CD18 and its other binding partners are located in the first domain and are overlapping. ICAM-1 domain 2 seems to play an important role in maintaining the conformation of domain 1 and particularly the structural integrity of the LFA-1 ligand-binding site [PMID: 10998349].

The 3-dimensional atomic structure of the tandem N-terminal Ig-like domains (D1 and D2) of ICAM-1 has been determined to 2.2A resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex [PMID: 9539703]. Extensive charge interactions between ICAM-1 and human rhinovirusesare largely conserved in major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is mediated by a divalent cation bound to the insertion (I)-domain on the alpha chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs.

ICAM-2 (CD102) has two Ig-like domains. It is expressed on endothelial cells, leucocytes and platelets, and binds to CD11a'b/CD18. The protein is refractory to proinflammatory cytokines, and plays an important role in the adhesion of leucocytes to the uninduced endothelium [PMID: 10352278].

ICAM-3 (CD50) contains five Ig-like domains and binds to leucocyte integrins CD11a'd/CD18. The protein plays an important role in the immune response and perhaps in signal transduction [PMID: 10725740].

ICAM-4 (LW blood group Ag) is red blood cell (RBC) specific and binds to CD11a'b/CD18. It is associated with the RBC Rh antigens and could be important in retaining immature red cells in the bone marrow, or in the uptake of senescent cells into the spleen [PMID: 10846180].

ICAM-5 (telencephalin) has nine Ig-like domains and is confined to the telencephalon of the brain. The role of this CD11a/CD18 binding molecule is not yet known [PMID: 10741396].

VCAM-1 was first described as a cytokine-inducible endothelial adhesion molecule. It can bind to leucocyte integrin VL-4 (very late antigen-4) to recruit leucocytes to sites of inflammation [PMID: 11133225]. The predominant form of VCAM-1 in vivo has an N-terminal extracellular region comprising seven Ig-like domains [PMID: 7531291]. A conserved integrin-binding motif has been identified in domains 1 and 4, variants of which are present in the N-terminal domain of all members of the integrin-binding subgroup of the immunoglobulin superfamily. The structure of a VLA-4-binding fragment comprising the first two domains of VCAM-1 has been determined to 1.8A resolution. The integrin-binding motif is exposed and forms the N-terminal region of the loop between beta-strands C and D of domain 1 [PMID: 7531291]. VCAM-1 domains 1 and 2 are structurally similar to ICAM-1 and ICAM-2 [PMID: 11133225].

This entry represents the N-terminal domain of both intercellular adhesion molecules (ICAM) and of vascular cell adhesion molecules (VCAM), which are structurally similar.

GO terms

Biological Process

GO:0098609 cell-cell adhesion

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.