CD322 JAM-2 (junctional adhesion molecule-2)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
Endothelial Cell
B Cell
T Cell
Tongue
Heart
Lung
Placenta
Lymph Node
Kidney
Testis
Leukocyte
Platelet
45 / 45

Expression
CD322 is expressed on endothelial cells, B cells, monocytes and T cell subsets. (probably activated and memory T cells).  It is strongly expressed during embryogenesis and becomes restricted in expression in adult tissues such as tongue and heart.  CD322 is located on the plasma membrane.  Highest expression is in the placenta, lung, and lymph node.  Expression is prominent in lymphoid organs, testis, and kidney.  Immunohistochemistry indicates that the CD322 protein is highly expressed on leukocytes or platelets.  It is expressed in endothelial cells in association with CD321 (JAM-1) and CD323 (JAM-3).  Expression is high on endothelial venules and lymphatic sinuses in lymphoid organs. 

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

CD322 is a single-pass type-1 279 aa glycoprotein.  It contains a 31 aa signal sequence, a 210 aa extracellular portion which contains 1 Ig-like distal V-type domain, 1 Ig-like C2-type domain, 4 conserved cysteines and 2 N-linked glycosylation sites, a 21 aa transmembrane domain and a 48 aa intracellular cytoplasmic domain which contains 4 putative phosphorylation sites.  The phosphorylation at serine 281 appears to be involved in the negative-regulation of CD322 localization in tight junctions.  CD322 is homologous with junctional adhesion molecules, CD321 (JAM-1) and to CD323 (JAM-3).  High homology between CD322 (JAM-2) and CD323 (JAM-3) defines a new family of adhesion proteins with a V-C2 immunoglobulin domain organization similar to that of the CTX molecular family. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
various 45 kDa 45 kDa Occurs with SDS-PAGE

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD322 has 2 potential N-linked glycosylation sites.


Ligands
CD322 associates with PAR-3, α4β1 integrin and CD323 (JAM3) and displays homophilic binding.

LIGANDS AND MOLECULES ASSOCIATED WITH CD322
Molecule Comment
ZO-1 In MDCK cells, JAM-2 co-localizes with ZO-1 and occludin, 2 components of tight junctions, indicating that JAM-2 is specifically associated with subcellular junctional complexes in epithelial cells
occludin In MDCK cells, JAM-2 co-localizes with ZO-1 and occludin, 2  components of tight junctions, indicating that JAM-2 is specifically associated with subcellular junctional complexes in epithelial cells



Function
CD322 associates with CD323 and CD321 and plays a role in the formation and maintenance of tight junctions and cell polarity of endothelial cells.  The localization of CD322 at tight junctions is regulated by serine phosphorylation and recruits cell polarity protein  PAR-3 and other tight junction protein ZO-1.  Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space.  The protein encoded by this immunoglobulin superfamily gene member, CD322, is localized in the tight junctions between high endothelial cells.  CD322 is important for cell-cell adhesion ligand and plays a central role in the interaction with a variety of immune cell types and may play a role in regulation of transendothelial leukocyte homing/migration to secondary lymphoid organs.  CD322 may promote the transmigration of human leukocytes across endothelium by homophilic interaction.
 
The dynamics of CD322 localization to cell-cell contacts was explored using the CD322 protein fused to green fluorescent protein and time lapse video microscopy.  Time lapse imaging of JAM-2-EGFP during the formation of cell-cell contacts showed that the protein was located within minutes to the contacts between cells.  Upon partial cell-cell contact, the JAM-2 enriched membrane closed in a "zipper like" fashion, indicating that JAM-2 homophilic interaction is an early event in the establishment of cell connections and may play a role in cell-cell contact organization.  The latter hypothesis gains further support from para-cellular permeability experiments in CHO cell transfected with JAM-1 EGFP or JAM-2 EGFP.  Both transfected cells present a reduced para-cellular permeability as demonstrated by the decrease in FITC dextran diffusion compared to the wild type.  A similar reduced para-cellular permeability was described following transfection of VE-cadherin and JAM-1, 2 molecules participating in adherens and tight junctions respectively.  When expressed in MDCK cells, JAM-2 was co-localized by immunofluorescence with ZO-1 and occludin, and 2 components of tight junctions, indicating that JAM-2 is specifically associated with subcellular junctional complexes in epithelial cells.  These results show that JAM-1 and JAM-2 not only have sequence similarities, but also have similar properties in term of subcellular localization, permeability regulation and homophilic interactions.

BIOCHEMICAL ACTIVITY

CD322 has a homophilic interaction.

DISEASE RELEVANCE AND FUNCTION OF CD322 IN INTACT ANIMAL

CD322 is potentially involved in the junctional sealing of the vascular endothelium and in particular the high endothelial venules (HEV).  CD322 is expressed on HEV in the human tonsil and on a subset of human leukocytes, suggesting that CD322 plays a central role in the regulation of transendothelial migration.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD322: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD322: No information.

ADDITIONAL INSIGHTS

For further information see Johnson-Leger, C. A. et al (2002) Blood 100: 2479-2486.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene58494P57087
Antibodies

Revised June 25, 2008


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