CD54 ICAM-1(intercellular adhesion molecule-1)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Epithelial Cell
Cytokine
Endothelia
ATL cell
Blood Cell
Tumor Cell
Monocyte
Fibroblastic cell
B Lymphocyte
T Lymphocyte
80 / 80
114 / 114

Expression
CD54 is expressed typically at high levels on activated endothelia when activated by pro-inflammatory cytokines and at moderate levels on activated T and B lymphocytes and on monocytes but is absent from resting leukocytes.  CD54 is highly expressed on ATL cells and some solid tumor cells.  Inflammatory cytokines such as TNF, IL-1 and interferon g enhance the expression of CD54.  CD54 is expressed at a low level on epithelia and endothelia cells but is inducible expressed on certain epithelial, endothelia and fibroblastic cells.  A soluble form of CD54 is detectable in the blood.



Structure
MOLECULAR FAMILY NAME FOR CD54: Belongs to the immunoglobulin supergene family.

CD54 is a single-pass type-1 500 aa glycoprotein.  It contains an extracellular domain which contains 5 Ig-like C2-type domains, a transmembrane domain and a short cytoplasmic domain.  CD54 is closely related to CD50 (ICAM-3).  Both proteins have 5 Ig-like C2 domains in their extracellular regions with a 52% identity.  The 2 membrane-distal Ig domains of CD54 also share an ~34% identity with the extracellular portion of CD102 (ICAM-2).  Electron microscopy studies suggest that CD54 is a bent rod 18.7 nm in length.  The cell surface CD54 may exist as a non-covalently linked dimer.  A number of alternatively spliced forms of CD54 are expressed in the mouse.  These isoforms, which have a more restricted pattern of expression lack combinations of domains 2-4, but most still bind LFA-1.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Lymphocytes 90 kDa 95 kDa ?
Solid tumor cells 75-115 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD54 is heavily glycosylated.

Ligands
CD54, like CD50 and CD102, is a ligand for the leukocyte integrin CD11a/CD18 (LFA-1).  CD54 also binds the related integrins CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) and has been reported to bind hyaluronan (HA) and fibrinogen.  CD54 is a receptor for the major group of rhinoviruses and is one of the receptors on endothelium for Plasmodium falciparum-infected erythrocytes.  Others include CD36 and thrombospondin.  The CD11a binding site lies on the GFC b sheet of the membrane-distal domain 1.  Rhinoviruses bind an overlapping site on domain 1 and possibly on domain 2 whereas Mac-1 binds to domain 3.

LIGANDS AND MOLECULES ASSOCIATED WITH CD54
Molecule Comment
CD11a/CD18 (LFA-1)
CD11b/CD18 (Mac-1)
Rhinovirus
Unknown molecule on Plasmodium falciparum-infected erythrocytes



Function
CD54 is a major signaling adhesion molcule in inflammatory and immune reactions. There is binding to CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-I), fibrinogen, hyaluronan and CD43.  CD54/CD11a/CD18 (ICAM-1/LFA-1) interaction is required for effective antibody responses, T cell proliferation, and IL-2 secretion and plays a role in allograft rejection.  Expression of CD54 on endothelium enables migration of activated leukocytes from blood vessels to sites of inflammation.    Undifferential embryonic stem (ES) cells have increased CD54 expression in the presence of leukemia inhibitory factor (LIF), a member of the IL-6 family which can influence transcriptional regulation via STAT3.  It is suggested that the pattern of expression of CD54 has a role in defining the phenotype of both differentiated and undifferentiated cells.  CD54 reacts with CD11a/CD18 or CD11b/CD18 resulting in immune reaction and/or inflammation.  CD54 on antigen-presenting cells contributes to antigen-specific T cell activation, presumably by enhancing interactions between T cells and antigen-presenting cells.  CD11a/CD18 positive cells such as neutrophils bind this molecule on the endothelial cells of the vessel. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD54 IN INTACT ANIMAL

CD54 is a potential target for immunosuppression in transplantation.  Some monoclonal antibodies to CD54 can reduce the reperfusion injury and may be useful for preventing allograft rejection.  Serum levels of soluble CD54 is a potential useful indicator of inflammation infection and a variety of tumors.  In vitro CD54 can act as a receptor for P. falciparum infected erythrocytes to postcapillary venular endothelium.  Knockout mice have decreased neutrophil migration contact hypersensitivity and generation of mixed lymphocyte response and demonstrate resistance to septic shock.  CD54 is a receptor for a group of rhinoviruses and the binding site for these viruses overlaps the CD11a/CD18 binding site.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD54
Molecule Comment
AP-1 sites

Many others are known.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD54: No information.

ADDITIONAL INSIGHTS

The soluble form of CD54 may act as an inhibitor of immune reaction between malignant cells and CTL or NK cells. The soluble form or chimeric antibody could be useful as therapeutic agent in autoimmune diseases.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3383P05362
MouseA45815P13597X52264
RatD00913
Antibodies
15.2   View Reactivity
HA58   View Reactivity

Revised June 25, 2008


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