CD89 Fcα-R,  IgA- receptor
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Neutrophil
Monocyte
Blood Cell
T Lymphocyte
B Lymphocyte
Macrophage
Myeloid Cell
Granulocyte
Dendritic Cell
Eosinophil
Promyelocyte
45 / 45
100 / 100

Expression
CD89 is expressed on myeloid-lineage cells from promyelocytes to neutrophils, on activated eosinophils, granulocytes, dendritic cells and on alveolar and splenic macrophages.  CD89 is expressed on most phagocytic cells in blood and mucosal tissues.  It is also found on subpopulations of T and B lymphocytes. The a1 and a2 products are differentially expressed.  Whereas the a1 form is found on monocytes and neutrophils, the a2 form is expressed by alveolar macrophages.  Expression of CD89 is upregulated in the presence of IgA-complexes, TNF-α, IL-1β, GM-CSF, LPS and PMA but is downregulated in the presence of TGF-β and suramin. Only the a1 and a2 forms have been detected at the protein level.


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

CD89 is a single-chain type-1 266 aa glycoprotein.  It contains a secretory signal sequence, 2 extracellular domains containing Ig-like C2-type domains, a 19 aa putative transmembrane segment containing a charged Arg residue and a 41 aa cytoplasmic tail which is devoid of known signaling motifs and requires interaction with FcRγ-chain homodimers for CD89 mediated signal transduction and the charged arginine (Arg209) which is essential for this association.  The IgA binding site is located in the extracellular domain 1.  Soluble CD89 is detected in serum and retains its IgA binding capacity.  Genomic analysis suggests that CD89 is most closely related to the 2 Fcg receptors CD16 and CD64.  It is notable that there is a His residue at the equivalent position in CD64.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Monocyte 45-70 kDa 45-70 kDa
Neutrophil 55-75 kDa 55-75 kDa
Eosinophil 70-100 kDa 70-100 kDa
Alveolar macrophages 50-65 kDa 50-65 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 6 different isoforms.  The a1, a2 and a3 clones encode transmembrane proteins and are generated by alternative splicing of exons.  An a form, also derived from alternative splicing, has been found to have a cryptic leader sequence.  These 2 other forms have alternative sequences to the transmembrane segment and may code for soluble products.  Transcripts are lacking either the S2 mini-exon, the entire EC2 exon, or the 3' part of the EC2 exon.  There is a presence of mRNA instability sequences ATTTA or TTATTTA in the 3' untranslated region.

POST-TRANSLATIONAL MODIFICATION

CD89 is glycosylated.

Ligands
CD89 binds both IgA1 and IgA2 via their Fc regions.  CD89 associates with the g chain homodimer of Fc receptors.  This interaction involves the transmembrane segment of CD89 as shown by the mutation of Arg209, which presumably forms a salt bridge with the Asp residue in the transmembrane segment of the g chain.

LIGANDS AND MOLECULES ASSOCIATED WITH CD89
Molecule Comment
Common Fc receptor g chain Serves as a transducing unit
IgA1 Ligand
IgA2 Ligand



Function
CD89 encodes the receptor for the Fc region of IgA.  CD89 interacts with IgA-oponized targets and triggers several immunologic defense processes, including phagocytosis, degranulation, respiratory burst, killing of microorganisms, antibody-dependent cell-mediated cytotoxicity and stimulation of the release of inflammatory mediators.  CD89 is a myeloid receptor for monomeric, secretory IgA1 and IgA2 with a low affinity and binds serum.  Binding of IgA to CD89 initiates several immune effector function including phagocytosis, cytotoxicity, degranulation, the release of inflammatory cytokines,respiratory burst and killing of micro organisms.  CD89 associates with the common FcRg chain homodimer that acts as a signal transduction molecule possibly through tyrosine phosphorylation.  The differential expression of the a1 and a2 isoforms in blood leukocytes and alveolar macrophages may suggest their different roles in blood and mucosal defense.  The association of β2-integrin CD11b/CD18 (Mac-1) with CD89 is required for binding of sIgA to CD89 phagocytes.

BIOCHEMICAL ACTIVITY

CD89 binds both monomeric and polymeric forms of either IgA1 or IgA2 which are at the boundary between the Ca2 and Ca3 domains.

DISEASE RELEVANCE AND FUNCTION OF CD89 IN INTACT ANIMAL

More glycosylated forms are on activated eosinophils from allergic individuals and on neutrophils and monocytes from cirrhotic individuals.  CD89 is a potential marker for immunotherapy of infectious disease and malignancies.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD89: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD89: No information.

ADDITIONAL INSIGHTS

There is a need to define the functional form of CD89 in terms of ligand binding and signal transduction and the role of CD89 in the process of infectious diseases.  The mouse CD89 orthologue has not yet been characterized either at the protein or the DNA level.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2204P24071
Antibodies
A59   View Reactivity

Revised June 25, 2008


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