CD304 NRP1 (neuropilin-1), NRP, VEGF165R, BDCA4 (blood dendritic cell antigen 4)
   
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Dendritic Cell
Neuron
T Cell
Endothelial Cell
Heart
Placenta
Kidney
Carcinoma Cell
Nervous system
Liver
140 / 140

Expression
CD304 expression is on endothelial cells, neurons and several carcinoma cells.  High level of expression is found in lineage CD45dim and CD11c-CD123bright, CD45RA plasmacytoid dendritic cells and at lower leves in CD34 dim, CD45dim pre-plasmacytoid dendritic cells, and tonsillar CD3+, CD57+ and CD185 T cells.  Expression is also on CD4+/CD25+ T cells.  The expression of isoforms 1 and 2 does not overlap.  Isoform 1 is expressed by blood vessels of different tissues.  In the developing embryo, it is found predominantly in the nervous system.  In adult tissues, it is highly expressed in heart and placenta; moderately in lung, liver,skeletal muscle, kidney and pancreas and low in adult brain.  Isoform 2 is found in liver, hepatocytes, kidney and distal and proximal tubules.  Unlike CD303, CD304 is expressed by plasmacytoid dendritic cells after maturation.

Structure
MOLECULAR FAMILY NAME: Belongs to the neuropilin family.

CD304 is a single-pass type-1 902 aa glycoprotein.  It contains a 21 aa signal peptide, an 835 aa extracellular domain which contains 5 potential N-linked glycosylation sites and 2 N-terminal complement binding (CUB) which form β barrel structures, 2 F5/8 type homology domains and 1 C-terminal MAM domain which is responsible for dimerization, a 23 aa transmembrane domain and a 44 aa cytoplasmic domain.  Domains within the coagulation factor domains are invoved in cell adhesion.   CD304 was originally described as a receptor for the semaphorins with a role in axon guidance.  

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  The soluble isoform consists of the CUB and F5/8 homology domains.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD304

CD304 is a receptor for semaphorin-3A, vascular endothelial growth factor A and plexin-1.

Function
CD304 on endothelial cells and tumor cells acts as a membrane coreceptor to vascular endothelial growth factor (VEGF) and semaphorins (SEMA) and plays a major role in angiogenesis and cell survival, migration and invasion.  CD304 mediates endothelial cell chemotaxis.  CD304 is a coreceptor with plexin and axonal guidance. CD304 is involved in neuritogenesis.  CD304 is a marker of plasmacytoid dendritic cells and is reported that it might be essential for the initiation of the primary immune response mediating interactions between dendritic cells and T cells. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD304 IN INTACT ANIMAL

CD304 is a neuronal receptor in the development of the cardiovacular system, in angiogenes, in the formation of certain neural curcuits and in organogenesis outside the nervous system.  Isoform 1 mediates the chemorepulsant activity of semaphorins.  It binds to semaphorin 3A, the PLGF-2 isoform of PGF, the VEGF-165 isoform of VEGF and VEGF-B.  Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis.  Many tumors including breast and prostate carcinomas express CD304 but corresponding nonmalignant tissues do not.  Studies have shown CD304 is involved in tumor angiogenesis, metastasis and tumor cell survival but over-expression of CD304 correlates with metastatic disease and poor prognosis for prostate cancer patients  The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells.  It may  induce apoptosis by sequestering VEGF-165.  Also it may bind various members of semaphorin family.  Its expression has an effect on blood vessel number and integrity. 

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD304: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD304: No information.

ADDITIONAL INSIGHTS

For further information see Dzionek, A. et al (2002) Hum. Immunol. 63: 1133-1148.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8829O14786
Antibodies

Revised June 25, 2008


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