|CD121a||IL-1R, IL-1R Type 1|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|80 / 80|
|CD121a is expressed on T cells, thymocytes, chondrocytes, synovial cells, hepatocytes, endothelial cells and keratinocytes. Expression is low on fibroblasts, lymphocytes, hematopoietic and other tissues, monocytes, macrophages, granulocytes, and dendritic, epithelial and neural cells.|
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.|
CD121a is a single-pass type-1 glycoprotein. It contains a 317 aa extracellular domain which contains 3 Ig-like C2-type domains and 6 potential N-linked glycosylation sites, a 19 aa transmembrane domain and a 213 aa cytoplasmic domain that is highly conserved across species with a 78% sequence identity between human and mouse and is necessary for signal transduction. The N-terminal IgSF domain of CD121a is encoded by an exon flanked 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 of CD121a has been identified. The molecule has a 28% aa sequence identity with CD121b.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
POST-TRANSLATIONAL MODIFICATION: No information.
|LIGANDS AND MOLECULES ASSOCIATED WITH CD121a|
CD121a binds IL-1a, IL-1β, and IL-ra but with different affinities. 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 CD12a1 from human, mouse and rat. A complex of CD121a and IL-1R AcP forms a high affinity IL-1 binding site at the cell surface. Alternative splicing of the IL-1R AcP gene may generate a soluble form of the molecule. There is an IL-1 receptor antagonist, IL-1ra, that inhibits the function of IL-1 in vivo and in vitro by binding CD121a. The IL-1ra is unable to stimulate kinase activity or the internalization of CD121a.
|CD121a is the IL-1 receptor and mediates all effects of IL-1α and IL-1β. It functions in association with the IL-1 receptor accessory protein (AcP) which enhances the affinity for IL-1 and initiates signaling. CD121a associates with IL-1RAcP and mediates IL-1 signaling. IL-1R mediates thymocyte and T cell activation, fibroblast proliferation, induction of acute phase proteins and inflammatory reactions through bindings to CD121a. IL-1R is bound to CD121a on fibroblasts and induces phosphorylation of several proteins, including the EGF receptor and the heat shock protein p27. CD121a mediated signaling results in the activation of transcriptional factors including NF-κB, AP-1 and C/EBPb leading to expression of inflammatory proteins such as prostaglandins and inflammatory cytokines. Binding of the IL-1 receptor antagonist to CD121a prevents IL-1α and IL-1β from binding but does not induce any biological response of its own.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD121a IN INTACT ANIMAL
Soluble CD121a is a potential anti-inflammatory agent.
| The ST2 antigen, also termed T1 or Fit-1, has an ~25% aa sequence identity to CD121a. The extracellular region of ST2 contains 3 C2-set IgSF domains and the molecule exists in both 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. |
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD121a: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD121a: No information.
Database accession numbers
Revised June 25, 2008