CD204 MSR1 (macrophage scavenger receptor 1), SRA
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
Kupffer Cell
Macrophage
Lymph Node
Liver
Langerhans Cell
Brain
Dendritic Cell
220 / 220

Expression
CD204 is expressed by mononuclear phagocytes in various tissues including on alveolar macrophages, dendritic cells, Kupffer cells of the liver, splenic red pulp macrophages, sinusoidal macrophages in lymph nodes, interstitial macrophages and in perivascular macrophages in the human brain.  Isolated blood monocytes are negative but become positive after 3 days in culture.  Expression by microglia in normal adult human brain is controversial.  However in Alzheimer's disease CD204 is strongly expressed by microglia associated with amyloid deposits and ischemic lesions.  Dendritic cells such as interdigitating cells of lymphoid tissues and epidermal Langerhans cells are invariably negative.

Structure
MOLECULAR FAMILY NAME: Belongs to the scavenger receptor family.

CD204 is a single-pass type-2 glycoprotein.  It contains a 375 C-terminal extracellular domain which contains 102 aa scavenger receptor cysteine-rich domain (SRCR), a collagen-like domain followed by an α-helical coiled coil, a membrane-proximal spacer and 7 potential N-linked glycosylation sites, a transmembrane domain and a 50 aa cytoplasmic domain.

MOLECULAR MASS
Cell Type Unreduced Reduced
220 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms of the gene MSR1 encoding class A macrophage scavenger receptors.  These isoforms are macrophage-specific trimeric integral glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes.  The isoforms type 1 and 2, one long and one short, are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs).  They are different at the C terminus but retains the ligand binding capacity.  The isoform type 3 does not interalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2.  Type 3 has an altered intracellular processing and is trapped within the endoplasmic reticulum and is not expressed on the cell surface making it unable to perform endocytosis.  It can inhibit the function of isoforms type 1 and 2 when co-expressed, indicating a dominant negative effect, suggesting a mechanism for regulation of scavenger receptor activity in macrophages.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD204

CD204 associates with LDL uptake and LPS lipoproteins.  It binds acetylated and oxidized low desity lipoproteins, glycared collagen type IV, fibrillar bat-amyloid, advanced glycation end products, chondroitin sulphate, fucoidin, polyinosinic acid, apoptotic cells, myelin, lipopolysaccharide and lipotechoic acid.

Function
CD204 plays a role in the pathological deposition of cholesterol during atherogensis through the receptor mediating uptake of low density LDL and the recognition and elimination of pathogenic microorganisms.  CD204 also plays a role in endocytosis of macromolecules.  Comparison of the amino acid sequence of CD204 molecules from different animal species show a high degree of conservation which has hindered the ability to elicit strong immune responses for the generation of high affinity antibodies.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD204 IN INTACT ANIMAL

CD204 mediates the uptake of a wide variety of negatively charges macromolecules by mononuclear phagocytes and plays a role in both innate and acquired host defenses and has been implicated in many macrophage associated physiological and pathological processes including atherosclerosis and Alzheimer's disease.  CD204 knockout mice are more susceptible to endotoxic shock and infection by some bacterial pathogens such as L. monocytogenes and do not mount efficient T cell responses.  CD204 deficient mice are less susceptible to diet-induced atherosclerosis than wild-type mice, suggesting a proatherogenic role for CD204.  Rare germline mutations in the CD204 gene are reported to be associated with an increased risk of prostate cancer.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD204: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD204: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4481P21757NM-138715
Antibodies

Revised June 25, 2008


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