CD43 Leukosialin, SPN (sialophorin), gp95, leukocyte sialoglycoprotein, gpL115
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
Neutrophil
Thymocyte
B Lymphocyte
Plasma Cell
NK Cell
Granulocyte
Monocyte
Macrophage
Bone Marrow
Hematopoietic Cell
Lymphocyte
95 / 95
115 / 115
135 / 135

Expression
CD43 is expressed, typically at high levels, on all leukocytes and is upregulated on activated B lymphocytes but not on resting B lymphocytes.  CD43 is the major sialoglycoprotein on thymocytes, T cells and neutrophils but it varies between cell types.  Activation of lymphocytes and neutrophils leads to rapid shedding of CD43 molecules from the cell surface.  Expression is on plasma cells, NK cells, granulocytes, monocytes, macrophages, and bone marrow hematopoietic stem cells.  Activation of neutrophils leads to downregulation of CD43 as a result of proteolytic cleavage.  A soluble form of CD43, called galactoglycoprotein, is present in human serum.  CD43 is rapidly lost from the lymphocyte and neutrophil surface by proteolytic shedding after activation with various stimuli.  Different cell types express CD43 forms differing in the degree of sialylation of the O-linked oligosaccharide chains.



Structure
MOLECULAR FAMILY NAME: Belongs to the mucin family.

CD43 is a single-pass type-1 385 aa glycoprotein.  It contains a 245 aa extracellular region which contains 5 repeats of an 18 aa sequence rich in serine and threonine glycosylation and 1 N-linked glycosylation site in the membrane-proximal region, a 23 aa hydrophobic transmembrane domain and an 123 cytoplasmic domain with a number of serine residues that are phosphorylated to a low level and superphosorylated upon activation.  CD43 is highly O-sialylated.  The extracellular region has an extended structure of approximately 45 nm in length.  The coding sequence of CD43 is contained within a single exon.  The molecular weight of the molecule and its antigenicity varies, depending on the nature of the O-glycans
.
MOLECULAR MASS
Cell Type Unreduced Reduced
Resting T Lymphocytes 95 - 115 kDa 95 - 115 kDa
Activated T lymphocytes 115 - 135 kDa 115 - 135 kDa
Neutrophils 115 - 135 kDa 115 - 135 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Splicing in CD43 does not occur as there is a single-exon gene.

POST-TRANSLATIONAL MODIFICATION

CD43 has an extensive serine/threonine glycosylation of the entire extracellular region and a single N-linked glycan in the membrane-proximal part.  Constitutive phosphorylation on serine residues in the intracellular region on the level of phosphorylation increases upon cell activation.  A soluble form of CD43 called galactoglycoprotein is present in blood plasma, which is apparently produced by proteolytic cleavage or shedding of the extracellular region.

Ligands
The extracellular domain has been reported to interact with CD54, MHC class I, CD62P and hyaluronic acid and acts as a T cell counter receptor for CD169.  An interaction with albumin has also been reported. The membrane-proximal portion of the cytoplasmic domain mediates an association with the cytoskeleton.

LIGANDS AND MOLECULES ASSOCIATED WITH CD43
Molecule Comment
CD54 Somewhat controversial: it remains to be confirmed that this interaction is relevant under physiological conditions




Function
CD43 binds to CD54 to mediate adhesion and appears to be important for immune function and may be a part of a physiologic ligand-receptor complex involved in T cell activation and a role in neutrophil migration.  CD43 also appears to be an anti-adhesive ("barrier") molecule mediating repulsion between leukocytes and other cells due to its extended rod-like shape and the presence of a large number of negative sialic acid residues.  Alternatively, under some circumstances, there is speculation that CD43 may act as an adhesion molecule possibly via its interaction with CD54 or with some lectin receptors.  In migrating leukocytes, CD43 via its intracellular domain interacts with actin-binding proteins moesin and ezrin and is subsequently redistributed to uropods, which the cell uses for traction during migration.  CD43 promotes T cell activation and proliferation by inducing IL-2 and CD69 expression.  IL-2 production is dependent on a functional intracellular domain.  It acts as a T cell counter-receptor for the macrophage-adhesion receptor CD169 (sialoadhesin/Siglec-1).  Ligation of CD43 by specific mAbs may induce activation in monocytes and apoptosis in hematopoietic progenitors.  Knockout mice show increased T-cell adhesion and easier activation.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD43 IN INTACT ANIMAL

Abnormally low and abnormal CD43 expression has been reported in T cells of patients with Wiskott-Aldrich syndrome, but this is only a secondary consequence of the primary defect in the gene responsible for this disorder.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD43
Molecule Comment
Sp1 Tissue specific expression is achieved by DNA methylation in the 5'-region of the CD43 gene.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD43
Molecule Comment
Protein kinase C Phosphorylation of the intracellular region after cell activation

ADDITIONAL INSIGHTS

An important unresolved question is how CD43 signals under physiological conditions and what is the physiological trigger for this signaling.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 6693P16150
MouseA43545P15702X17018
RatS00842P13838Y00090
Antibodies
1G10   View Reactivity
CO.44B8   View Reactivity
DFT-1   View Reactivity
L11/135   View Reactivity

Revised June 25, 2008


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