CD88 C5a-R, C5R1 (complement component 5a receptor 1)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Epithelial Cell
Spleen
Muscle, Smooth
Hepatocyte
Macrophage
Endothelial Cell
Dendritic Cell
Granulocyte
Monocyte
Neutrophil
Astrocyte
Lung
Heart
Kidney
Small intestine
43 / 43

Expression
CD88 is expressed on granulocytes, monocytes, dendritic cells, the hepatoma-derived cell line HepG2, astrocytes and microglia.  It is also expressed on hepatocytes and on many cell types in the lung, including bronchial and alveolar epithelial cells, alveolar macrophages and vascular endothelial cells. CD88 mRNA has also been detected in the heart, spleen, kidney and intestine but the cell types expressing CD88 have not been identified.  C5a is expressed on human neutrophils. Receptors for the chemoattractants C5a and IL-8 are clustered on the surface of human neutrophils.


Structure
MOLECULAR FAMILY NAME: Belongs to the rhodopsin superfamily.

CD88 is a multi-pass type-3, 7 span 350 aa glycoprotein.  It is a typical G protein-coupled receptor which contains 7 hydrophobic transmembrane-spanning domains.  CD88 is related to the CD128 molecule and the N-fomyl peptide receptor. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Neutrophil 43 kDa
Monocytes 43 kDa

POST-TRANSCRIPTIONAL MODIFICATION:No information.

POST-TRANSLATIONAL MODIFICATION

CD88 is glycosylated and is phosphorylated in response to C5a or after stimulation of cells with phorbol esters.

Ligands
CD88 binds anaphylatoxin and  C5a/5a (des Arg) which is the N-terminal fragment with 74 residues in the human of the a chain of the complement component C5.  This fragment is proteolytically cleaved from C5 during complement activation. CD88 is coupled to heterotrimeric G proteins inside the cell.  In neutrophils, CD88 appears to couple exclusively to the G proteins Gia2 and Gia3, which are pertussis toxin sensitive.

LIGANDS AND MOLECULES ASSOCIATED WITH CD88
Molecule Comment
C5a/C5a(desArg)
Anaphylatoxin



Function
CD88 is a G-protein-coupled receptor involved in C5a-mediated inflammation and activation of granulocytes.  The CD88 residue Asp-282 near the extracellular face of the transmembrane domain VII, is a component of the ligand-binding site responsible for C5 receptor activation.  The binding of C5a to CD88 on neutrophils leads to a number of effects including with increasing C5a concentrations, cytoskeletal remodeling, shedding of selectins, upregulation of adhesion molecules, chemotaxis, granule exocytosis and activation of NADPH oxidase. 

BIOCHEMICAL ACTIVITY

The C5a occupied receptor stimulates the GTPase activity of Gi2.

DISEASE RELEVANCE AND FUNCTION OF CD88 IN INTACT ANIMAL

A role in mucosal defense to infection is indicated by the failure of CD88 knockout mice to clear Pseudomonas aeruginosa introduced directly into the trachea.  Neutrophil migration into the lung is elevated while migration into the peritoneum in response to glycogen-induced inflammation is decreased.  It is thought that CD88 may have a therapeutic role in antiphospholipid syndrome, a recurring pregnancy loss and thrombosis disease.
 

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD88: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD88: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 728P21730
MouseP30993S46665
Antibodies
P12/1   View Reactivity
S5/1   View Reactivity
W17/1   View Reactivity

Revised June 25, 2008


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