CD180 LY64 (lymphocyte antigen 64 homolog), RP105, Bgp95
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
B Cell
Peripheral blood
Monocyte
Dendritic Cell
Lymph Node
Plasma Cell
95 / 95
100 / 100

Expression
CD180 is strongly expressed on mantle, marginal zone and peripherical B cells, but is weakly or negatively expressed on germinal center B cells and not detected in pre-B and T cells.  It is also expressed on peripheral blood monocytes, dendritic cells and on the plasma membrane.  In the mouse expression is mainly on mature IgM+ and IgD+ B cells.  Expression is also detected in spleen, lymph node and appendix.

Structure
MOLECULAR FAMILY NAME:  Belongs to the Toll-like receptor family.

CD180 is a single-pass type-1 661 aa glycoprotein.  It contains a putative signal sequence, an extracellular domain which contains 17 leucine-rich repeats (LRR) that consist of 24-28 aa tandem repeats of a leucine-rich motif (LRM) in which leucines are characteristically positioned, a transmembrane domain and a short cytoplasmic domain which contains a 11 aa sequence and includes 2 tyrosine residues.  The extracellular repeats are associated with a molecule called MD-1 and forms the cell surface receptor complex, RP105/MD-1.  It belongs to the family of pathogen receptors, Toll-like receptors (TLR).  RP105/MD-1, by working in concert with TLR4, controls B cell recognition and signaling of lipopolysaccharide (LPS), a constituent of Gram-negative bacteria.  Some proteins that contain LRR molecules are used for pathogen recognition in organisms as divergent as plants, flies, mice and humans.

MOLECULAR MASS
Cell Type Unreduced Reduced
B Cells 95-105 kDa 95-105 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD180
Molecule Comment
MD-1 CD180 is associated with MD-1


Function
CD180 regulates LPS recognition and signaling and B cell activation.  Ligation of CD180 on murine B cells like CD40 ligation by a mAb induces activation that leads to upregulation of co-stimulatory molecules, CD80 and CD86 and an increase in cell size.  CD180 stimulation makes B cells more susceptible to BCR induced cell death but not to CD95 induced apoptosis.  Ligating CD40 has the opposite effect rendering B cells more susceptible to CD95 mediated death.  Ligating CD180 on human B cells alone can induce B cells to enter G1 phase of the cell cycle and then proliferate.  CD180 may play a role in the transmission of a growth-promoting signal.  CD180 leads to NF-κB activation and is involved in the life/death decision of B cells.  B cells from null mice lacking CD180 are impaired in LPS-induced proliferation and antibody production. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD180 IN INTACT ANIMAL

Decreased expression of CD180 has been shown in systemic lupus erythematosus (SLE).  The loss of CD180 is associated with B cell activation and increased disease activity in SLE patients.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD180: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD180: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4064Q99467
Antibodies
G28-8   View Reactivity

Revised June 25, 2008


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