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Protein Domain : IPR013768

Name  Intercellular adhesion molecule, N-terminal Short Name  ICAM_N
Type  Domain Description  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 []. 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 [].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 []. 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 [].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 [].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 [].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 [].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 []. The predominant form of VCAM-1 in vivo has an N-terminal extracellular region comprising seven Ig-like domains []. 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 []. VCAM-1 domains 1 and 2 are structurally similar to ICAM-1 and ICAM-2 [].This entry represents the N-terminal domain of ICAM proteins such as ICAM-2, ICAM-3 and ICAM-4.

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1 Cross References

Source . Name

Subject . Primary Identifier
PF03921 PFAM IPR013768

1 Data Sets

Name URL
InterPro data set  

3 Found In

DB identifier Name Short Name Type
IPR013783 Immunoglobulin-like fold Ig-like_fold Domain
IPR015653 Intercellular adhesion molecule 2 ICAM2 Family
IPR003987 Intercellular adhesion molecule/vascular cell adhesion molecule, N-terminal ICAM_VCAM_N Domain

0 GO Annotation

0 Ontology Annotations

0 Parent Features

0 Proteins