|CD64A||FcγRI, FcR I|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|72 / 72|
|CD64 is constitutively expressed on monocytes, macrophages and a subset of blood cells. Expression on monocytes can be strongly upregulated by treatment with IFN-g or G-CSF and PMN is also activated by the same treatment. Expression of CD64 can be induced by IFN-g on neutrophils and eosinophils. CD64 is also expressed on germinal center dendritic cells and on early myeloid lineage cells. B and C gene transcripts have been identified in monocytic cells. B2 transcripts are detected in all cells that express the A form of CD64, but a B2 protein has not been detected at the protein level. |
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.|
CD64 is a single-pass type-1 glycoprotein. It contains a extracellular domain which contains 3 Ig-like C2-type domains, a transmembrane domain and a cytoplasmic domain which has an unique tail which is suspected to have signaling properties but no signaling motif has yet been identified. CD64 is involved in receptor-mediated endocytosis of the IgG antigen complexes. In humans, there are 3 related genes. The A gene encodes the high affinity Fcg receptor, a A cDNA clone has been identified which encodes a variant of the A form (A') with a different cytoplasmic domain, but this alternative sequence is not present in the gene sequence. The B and C genes are very similar to the A gene except both contain stop codons in the 3rd Ig-like domain, suggesting that they encode soluble proteins with 2 Ig-like domains. B and C gene transcripts have been identified in monocytic cells. An alternatively spliced form of the B gene, B2, is similar to the A form but lacks the 3rd Ig-like domain. A 3rd alternatively spliced form of the B gene has also been identified but with a cryptic leader sequence. The Fcg RIA gene product has 3 extracellular Ig-like domains. MAbs identified to date react only with the Fcg RIA gene product which has a high affinity for IgG. Fcg RIA-encoded protein is expressed as a multi-subunit receptor and requires the association with g:g homodimers g chain of the IgE receptor to mediate phagocytosis.
Alternative splicing yields 2 different isoforms. FcgRIB has alternative sites yielding Fcg Rlb1 and Ib2.
FcgRIA-encoded protein is highly glycosylated. The RIB and RIC genes encode glycosylation sites but proteins have not been characterized.
|CD64 is the high affinity Fcg receptor and binds monomeric, as well as aggregated, IgG. CD64 associates with the g chain homodimer of Fc receptors, possibly through the interaction between the His in CD64 and the Asp in the g chain in their respective transmembrane regions. The kinases Hck and Lyn can also be co-immunoprecipitated with CD64 from cell lysates.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD64
|CD64 is a receptor for Fc segment of the IgG mediating phagocytosis and plays a role in immune response and a role in antibody-dependent cellular cytotoxicity and clearance of immune complexes. CD64 functions in phagocytosis as a high affinity receptor mediated endocytosis of IgG antigen oponized complexes. It also functions as an antigen capture for the presentation to T cells and also mediates release of cytokines and reactive oxygen intermediates including IL-1, IL-6, and TNFa. The association of CD64 with the Fc receptor g chain homodimer is required for its signal transduction activity. It has been shown that ligation of CD64 results in an increase in the Hck and Lyn kinase activities. Although a B2 form has not been identified at the protein level, transfection of the B2 cDNA into COS cells showed binding to aggregated IgG but not monomeric IgG. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD64 IN INTACT ANIMAL
A non-sense mutation in the CD64 A gene has been identified. Because individuals homozygous for this mutation are apparently healthy, and the level of the B2 transcript is consistently high in their blood monocytes, it was speculated that the B2 form of CD64 may be functional. Increased PMN expression is associated with infectious diseases and therapy with IFN-g or G-CSF. CD64 protein is absent in one Belgian family with no marked disease consequences.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD64
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD64: No information.
PE-CY5 tandem conjugates bind specifically to CD64, leading to a high background staining of CD64+ cells.
Database accession numbers
Revised June 25, 2008