|CD120a||TNFR1 (tumor necrosis factor receptor 1), TNFp55, TNFRSF1A|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|Epithelial Cell||50 / 50|
60 / 60
|Most cell types express the receptors CD120α and CD120β for TNF. CD120α is constitutively expressed at a low level on hematopoietic and non-hematopoietic cells. Expression is high on epithelial cells.|
|MOLECULAR FAMILY NAME: Belongs to the tumor necrosis factor family.|
CD120α is a single-pass type-1 glycoprotein. It contains an 190 aa extracellular domain which contains 4 tandemly repeated cysteine rich motifs and has 3 potential N-linked glycosylation sites, a transmembrane domain and a 221 aa intracellular cytoplasmic domain which has an 86 aa death domain and an 11 aa neutral sphingomyelinase activation domain known to be involved in apoptotic signaling. The extracellular domain has a pre-ligand-binding assembly domain that promotes the formation of receptor complexes and trimerization of CD120α molecules particularly after activation by ligand binding. The structure of the extracellular domain of CD120α has also been determined in the absence of ligand, and it forms a dimer but it is not known, whether this occurs at the membrane. The structure of a complex between the trimeric lymphotoxin a (LTa) and 3 molecules of the extracellular domain of CD120α has been determined by X-ray crystallography.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
Phosphorylation of CD120α occurs at a consensus mitogen activated protein kinase (MARK) site within the cytoplasmic domain or at tyrosine residues.
|LIGANDS AND MOLECULES ASSOCIATED WITH CD120α|
Both receptors bind TNFa and LTa with a relatively high affinity of kDa < 10-9 M-1. The membrane bound and soluble TNF and LTa bind to CD120β. A 3rd TNF-like protein, lymphotoxin b (LTb) forms heterocomplexes with LTa at the cell surface but these do not bind CD120β but to a separate LTb receptor. Several different proteins can associate directly or indirectly with the cytoplasmic parts of CD120β, including TNF receptor-associated factors (TRAF), TNF receptor-associated proteins (TRAP), TNF receptor-associated kinase (TRAK) and TNFR1-associated death domain protein (TRADD).
|CD120α is a receptor for tumor necrosis factor, binding both membrane-bound and soluble forms of TNFa and TNFβ with high affinity. Intracellular adaptor proteins are know to associate with CD120α. Signal transduction via these molecules mediates proinflammatory cellular responses apoptosis and anti-viral activity. Crosslinking of the TNF receptors by soluble or membrane bound TNF leads to signaling which is mediated by a variety of associated molecules leading to different pathways. Signaling is mainly mediated through CD120α. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD120α IN INTACT ANIMAL
CD120α mediates a wide variety of effects including tumor necrosis, anorexia, fever, induction of other cytokines, cell differentiation and apoptosis. CD120α play a major role in early graft versus host disease and in TNF mediated insulin resistance seen in the treatment of type II diabetes millitus thereby becomes a potential therapeutic target in the treatment. Defects in CD120α are the cause of autosomal dominant familial Hibernian fever (FHF), also known as TNF-receptor associated periodic syndrome (TRAPS). CD120α knockout mice were more susceptible to infection with Listeria monocytogenes but are resistant to TNF- or IL-1-mediated in vivo lethality and are also resistant to LPS- or D-galactosamine induced endotoxic shock.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD120α: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD120α: No information.
Database accession numbers
Revised June 25, 2008