CD312 EMR2 (epiderman growth factor-like module containing mucin-like hormone receptor 2)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Neutrophil
Monocyte
Macrophage
Dendritic Cell
Lymphocyte
Spleen
Myeloid Cell
Lymph Node
Leukocyte
Peripheral blood
Jurkat cell
90 / 90

Expression
CD312 is expressed on myeloid cells, neutrophils, activated monocytes/macrophages, Jurkat cell lines, dendritic cell subsets, activated lymphocytes and low on granulocytes.  The highest expression was found in peripheral blood leukocytes followed by spleen and lymph nodes.  Intermediate to low levels are found in thymus, bone marrow, fetal liver, placenta and lung.  There is no expression in heart, brain, skeletal muscle, kidney or pancreas.

Structure
MOLECULAR FAMILY NAME: Belongs to the G-protein coupled receptor 2 family.

CD312 is a multi-pass type-3 7-span 823 aa glycoprotein.  It contains a 23 aa signal sequence, a N-terminal extracellular domain which contains 5 EGF-like domains and 8 N-linked glycosylation sites, a 7-span 248 aa transmembrane domain and a 41 aa cytoplasmic domain which has 4 potential phosphorylation sites.  CD312 is a G-protein-coupled receptor and is expressed predominately by cells of the immune system.  Family members are characterized by an extended extracellular region with N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain.  The 5 EGF-like domains are nearly identical to those of CD97 and multiple N- and O-glycosylation sites and 1 GPS domain.  The first two EGF domains of CD97 bind CD55 but not CD312, domains 2 through 5 have calcium-binding sequences likely to play important roles in protein-protein interactions.  The fourth EGF domain of CD312 and CD97 interacts with the glycosaminoglycan chondroitin sulphate (CS), where the ligand is specifically found on B cells within the peripheral blood, on activated lymphocytes and myeloid cells.  The spacer domain contains a cysteine-rich motif involved in proteolytic cleavage.  The GPS domain is necessary but not sufficient for receptor cleavage, which require the extra extracellular stalk. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 1 isoform.

POST-TRANSLATIONAL MODIFICATION

CD312 is post-translationally autocatalytically cleaved at a G-protein-coupled receptor proteolytic site (GPS) motif into 2 subunits.  The α subunit is in the N-terminal extracellular EGF-domains and the second subunit is located in the 7-span transmembrane domain.  The subunits form a heterodimer noncovalently linked via an extended spacer domain.
CD312 has 8 N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD312

CD312 binds with chondroitin sulfate (CS), glycosaminoglycan (GAG) and dermatan sulphate (CD55).

Function
A recent study suggests CD312 may play a role in the interaction of activated T cells, dendritic cells and macrophages with B cells which express the glycosaminoglycan (GAG) chondroitin sulphate.  CD312 is predicted to play a role in cell adhesion and migration for phagocytosis as well as involement in immune and inflammatory responses.  This protein does not interact with the ligand decay accelerating factor(CD55) for complement, unlike the related CD97 antigen, and indicates that these very closely related proteins likely have nonredundant functions.  This gene results in multiple transcripts encoding distinct isoforms. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD312 IN INTACT ANIMAL

A recent study found significantly higher expression of CD312 in synovial tissue from rheumatoid arthritis patients than patients with osteoarthritis or reactive arthritis.  The majority of CD312 cells expressing TNFα and costimulatory molecules.  CD312 mediated binding of these cells to dermatan sulfate in the synovium.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD312: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD312: No information.

ADDITIONAL INSIGHTS

For further information see Kwakkenbos,M. J. et al (2004) J. Leukoc. Biol. 77:(1):112-119.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene30817Q9UHX3
Antibodies

Revised June 25, 2008


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