CD234 DARC (Duffy blood group, chemokine receptor),FY-glycoprotein
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Erythrocyte
Endothelial Cell
Erythroid Cell
Neuron
Kidney
Spleen
Liver
Bone Marrow
Thyroid
36 / 36

Expression
CD234 is expressed on a subset of endothelial cells of postcapillary venules and several tissues.  CD234 can be upregulated on these cells at sites of inflammation.  It is suggested that chemokines may be presented by CD234 on the surface of activated endothelial cells.  It is expressed on erythrocytes, epithelial cells of the kidney collecting duct, lung alveoli and thyroid, and on neurons (Purkinje cells) in the cerebellum.  Decreased neutrophil mobilization is found following intraperitonal injection of LPS in Fy-null mice.  CD234 is expressed in adult kidney and spleen, bone marrow and fetal liver.  Expression is found along postcapillary venules throughout the body, except in the adult liver.  Erythroid cells and postcapillary venule endothelium are the principle tissues expressing Duffy.  FY(-A-B) negative individuals do not express Duffy in the bone marrow, however they do, in postcapillary venule endothelium.

Structure
MOLECULAR FAMILY NAME: Belongs to the chemokine receptor superfamily.

CD234 is a multi-pass type-3, 7 span 338 aa Fy-glycoprotein.  It contains an extracellular domain which contains 2 N-linked glycosylation sites and 4 conserved Cys residues (at the N-terminus and the first, second and third extracellular loops) that are paired to form disulfides that help to stabilize the protein,  7 or 9 transmembrane domains which span the cytoplasmic membrane 7 times, carries antigenic determinants of the Duffy blood group system, which consists of 5 functional alleles and 1 silent allele, 5 phenotypes and 5 antigens.  The N-terminus is outside and the C-terminus is inside the membrane.  Ligand binding of CC chemokines has been located to a pocket formed by sequences in the 1st and 4th extracellular domains, brought into close proximity by a intrachain disulphide bridge and can be inhibited by Fy-6 antibodies.  Following chemokine binding, there is no signal transduction detectable by GTPase activity or intracellular calcium mobilization.  CD234 lacks the DRY motif in the 2nd cytoplasmic loop that is characteristic of G-protein couples heptahelical receptors.

MOLECULAR MASS
Cell Type Unreduced Reduced
35-45 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  The CD234 human transcriptional units encompasses 1,572 nucleotides including exon 1 of 55 nucleotides, a single intron of 479 nucelotides and exon 2 of 1,038 nucleotides.

POST-TRANSLATIONAL MODIFICATION

N-linked glycosylation sites are at Ans16 and Ans27 on the exocellular amino terminal domain.  The cloned CD234 also has 4 conserved Cys residues at the N-terminus at the 1st, 2nd and 3rd exocellular loops that are paired to form disulfides that help to stabilize CD234.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD234

CD234 associates with CXCL1, 5, 8 and CCL2, 5 and 7.  It is the human receptor for the malarial parasites Plasmodium vivax and knowlesi.
 
Molecule Comment
IL-8 CD234 is a binding protein for some chemokines including IL-8, MGSA, RANTES and MCP-1
MGSA CD234 is a binding protein for some chemokines including IL-8, MGSA, RANTES and MCP-1
RANTES CD234 is a binding protein for some chemokines including IL-8, MGSA, RANTES and MCP-1
MCP-1 CD234 is a binding protein for some chemokines including IL-8, MGSA, RANTES and MCP-1


Function
CD234, a carrier of the Duffy blood group system, is a chemokine decoy receptor and binds a number of chemokines of both the CC and the CXC families and such as GRO, RANTES, MCP-1, TARC and IL-8 which has a high affinity to modulate the intensity of inflammatory reactions.  Its physiological role might act as an intracellular sink to modulate the level of the pro-inflammatory molecules.  Studies of patients undergoing IL-2 immunotherapy revealed that plasma IL-8 levels reached a peak level after 4 hours and declined rapidly to undetectable levels within 8 hours.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD234 IN INTACT ANIMAL

Mice with a targeted disruption of CD234 lacked developmental abnormalities and were healthy at 1 year but lack CXC and CC chemokine-binding activity.  When challenged with lipopolysaccharide (LPS) resulted in significantly increased inflammation infiltrates in the lung and liver of CD234 null mice compared with wild-type mice.  However, when toxic doses of LPS were given, a decrease in leukocyte infiltration was found in the lungs and peritoneal cavity.  Other aseptic antigens such as thioglycolate and zymosan induced different responses.  CD234 plays a role in inflammation and in malaria infection and is the human receptor for the malaria parasites Plasmodium vivax and Plasmodium knowlesi which bind and enter erythrocytes.  Some individuals, usually African or African Americans carry a mutation in the FY gene that causes a T to C substitution in the promoter region.  This substitution disrupts binding of the h-GATA-1 erythroid factor and prevents expression of CD234 erythroid cells but not in non-erythoid cells.  The absence of CD234 renders the red cells resistant to infection.  Individuals that do not produce the Duffy antigen (FY[A-B]) are more resistant to vivax malaria.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD234: No information.

SUBSTRATES

No intrinsic catalytic domains are present in CD234.

ENZYMES WHICH MODIFY CD234: No information.

ADDITIONAL INSIGHTS

There is no evidence that CD234 can transduce a biological signal in endothelial cells.  It is interesting that a recent study has suggested that it might participate in transcytosis and surface presentation of IL-8 by venules endothelial cells.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2532Q16570
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University