CD121b IL-1R; Type2, CDw121b
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
B Cell
Monocyte
Macrophage
Neutrophil
T Cell
Skin
Epithelium
Basal Cell
60 / 60
68 / 68

Expression
CD121b is predominantly expressed on B cells, monocytes, macrophages, basal cells in the epithelium of the skin, female reproductive tract, ureter and neutrophils.  CD121b mRNA is present on a number of cells, including T cells.

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

CD121b is a single-pass type-1 glycoprotein.  It contains a 336 aa extracellular domain which contains 3 Ig-like C2-type domains and 5 N-glycosylation sites, a 20 aa transmembrane domain and a short 29 aa cytoplasmic domain.  The N-terminal IgSF domains of CD121b are encoded by an exon with the normal phase 1 intron/exon boundary at the N-terminus, but with an unusual phase 2 intron predicted between the F and G strands rather than after the G strand.  A soluble form is produced by proteolysis particularly after cell stimulation.  Soluble CD121b is present at very low concentration and has no biological function has been attritbuted to it.  CD121b has a 28% aa sequence identity with CD121a.

MOLECULAR MASS
Cell Type Unreduced Reduced
60-68 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD121b

CD121b binds IL-1β with a hig affinity and has low affinity for IL-1α and IL-1ra ( Il-1 receptor antagonists).  A 2nd subunit of the IL-1R complex has been cloned from mouse 3T3-L1 cells, the widely expressed IL-1R AcP.  There is an ~25% overall sequence homology between mouse IL-1R AcP and CD121b from human, mouse and rat.  There is an IL-1 receptor antagonist (IL-1ra) that inhibits the function of IL-1 in vivo and in vitro by binding to CD121b.

Function
CD121b appears to be dispensable as a negative regulator for IL-1 signaling and unlike CD121a, acts as a decoy receptor that inhibits the activity of its ligands and reduces the effective concentration of IL-1β.  It may play a role in the preventing toxicity in the presence of excessive systemic IL-1β producing cells from excessive autocrine stimulation.  IL-4 is reported to antagonize the activity of IL-1 by inducing the expression and release of this cytokine.

BIOCHEMICAL ACTIVITY: No information

DISEASE RELEVANCE OF AND FUNCTION OF CD121b IN INTACT ANIMAL

CD121b reduced levels of mRNA in the endometrium of women suffering from endometriosis revealing a profound defect in gene expression with reduced capability of endometrial tissue to downregulate IL-1 activity.  CD121b has the potential to be used as an anti-inflammatory agent and may be more effective that soluble CD121a as it has a low affinity for the IL-1 receptor antagonist IL-ra.


Comments
Vaccinia virus contains an open reading frame with strong resemblance to a soluble form of CD121b.  The ST2 antigen, also termed T1 or Fit-1,) has an ~25% aa sequence identity to CD121b. The extracellular region of ST2 contains 3 C2 IgSF domains and the molecule exists in both a soluble and membrane bound form.  ST2 does not appear to function as a receptor for either IL-1a, IL-1b or IL-1ra, but binds to a cell surface ligand expressed by a range of cell types.

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD121b: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD121b: No information.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7850P27930
MouseX85999
MouseP27931X59769
RatP43303Z22812
Antibodies

Revised June 25, 2008


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