CD212 IL12Rβ1 (interelukin 12 receptor, β1),
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
NK Cell
Lymphocyte
Monocyte
Tonsil
Skin
B Cell
Peripheral blood
Lymphoma Cell
Th1 Cell
85 / 85
110 / 110

Expression
CD212 is expressed on activated CD4+ and CD8+ T cells, IL-2-activated CD56+ NK cells, some B cell lines and gd T cells.  CD212 is expressed on peripheral blood lymphocyes, cord blood lymphocytes and subsets of monocytes.  Human tissue samples show positive mononuclear cells in the tonsil, skin lymphomas, Crohn disease and ulcerative colitis.  CD212 is expressed by Th1 cells but not by Th2 cells.

Structure
MOLECULAR FAMILY NAME: Belongs to the type 1 cytokine receptor family.

CD212 is a single-pass type-1 662 aa glycoprotein.  It contains an extracellular domain which contains 5 extracellular fibronectin type-3 domains with the second containing a WSXWS motif required for proper folding and surface expression and has 6 potential N-glycosylation sites, a 25 aa transmembrane domain and a 92 aa relatively short cytoplasmic domain which contains a box-1 motif which is essential for activation of the JAK signaling pathway.  It belongs to the hemopoietin receptor superfamily and combines with an unidentified peptide to form a heterodimer.  It shows a high degree of aa sequence similarity to CD130 gp130, CD114 G-CSFR and the LIFR a chain.  Crosslinking experiments using unlabeled human IL-12 and 125 I -labeled PHA-activated lymphoblasts have identified 2 proteins of approximately 110 kDa and 85 kDa which may associate to form a functional IL-12R.  The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
 
MOLECULAR MASS
Cell Type Unreduced Reduced
Lymphoblasts 110 kDa, 85 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
CD212 binds IL-12 but requires dimerization and complexing with the IL-12Rβ2 protein to give high affinity binding.  IL-12 has 3 classes binding sites which have been demonstrated on activated human T cells and the T cell line, Kit225 with a high affinity of kDa = 5-20 pM, an intermediate affinity of kDa = 50-200 pM and a low affinity of kDa = 2-6 nM. The IL-12R b chain binds both human and mouse IL-12 with an apparent affinity of kDa = 2-5 nM.


Function
CD212 dimerizes with the IL-12 receptor β-2 chain to form the functional IL-12 receptor.    CD212 is a tyrosine kinase membrane receptor for angiopoietin and is involved in cell signaling and immune regulation.  CD212 and IFN-gR1 signals coordinately regulate IFN-g production, but only IL-12 negatively controls IL-4 production.  IL-12 and IFN-g signals are each sufficient for inducing IFN-g production but both are needed for optimal production.  CD212 has pleiotropic effects on NK and T cells, including the stimulation of cell proliferation, induction of IFNg secretion, enhancement of cytolytic responses and promotion of a Th1-type immune response.  The protein which encodes CD212 binds to interleukin 12 with a low affinity and is thought to be a part of the IL-12 receptor complex.  This protein forms a disulfide-linked oligomer, which is required for its IL-12 binding activity.  The coexpression of this and CD212 proteins was shown to lead to the formation of high-affinity IL-12 binding sites and reconstitution of IL-12 dependent signaling. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD212 IN INTACT ANIMAL

CD212 identifies with Th1 cells.  Deficiency in this gene is associated with severe infection by Mycobacterium and other organisms including some that are weakly pathogenic in normal individuals.  CD212 has been reported to be upregulated in the chronic inflammatory disease Crohn's disease.  Defects in CD212 are the cause of mycobacterial disease known as familial disseminated atypical mycobacterial infection and Salmonella infections.


Comments
COS-7 cells transfected with the IL-12R b chain cDNA express both monomers and disulfide-linked dimers, or oligomers, of the IL-12R b subunit on their surface.  Oligomerization of the IL-12R b subunit is independent of IL-12, while the dimers/oligomers but not the monomers bind IL-12 with a low affinity of kDa = 2-5 nM.  A 2nd component of the functional IL-12R, designated IL-12R b2 subunit, has been characterized through the isolation of human and mouse cDNA clones.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD212: No information.

SUBSTRATES: No information

ENZYMES WHICH MODIFY CD212: No information.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3594P42701
MouseU23922
Antibodies

Revised June 25, 2008


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