|CD156b||ADAM17(a disintegrin and metalloproteinase domain 17), TACE(TFN α converting enzyme), CSVP(snake venom-like protease)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|93 / 93|
100 / 100
|CD156b is expressed on T cells, neutrophils, endothelial cells, monocytes, dendritic cells, macrophages, polymorphonuclear leukocytes and myocytes. Expression is wide in non-lymphoid tissues including heart, placenta, brain, muscle and is induced in cartilage in arthritis. CD156b is expressed on all cells examined with the pro-domain removed. The processed form, but not the unprocessed form, is downregulated in response to phorbol ester. CD156b is located on the plasma membrane and unidentified intracellular sites. CD156b is induced in the cartilage of arthritis.|
|MOLECULAR FAMILY NAME: Belongs to the disintegrain and metalloprotease family.|
CD156b is a single-pass type-1 824 aa transmembrane glycoprotein. It contains a 17 aa secretory signal sequence, an extracellular domain which contains an 18-214 aa pro-domain that is cleaved before the molecule becomes catalytically active, a 215-473 aa catalytic (zinc-dependent metalloprotease) domain, a 474-671 aa disintegrin-cysteine-rich domain, and 6 potential N-linked glycosylation sites, a 672-694 aa transmembrane domain and a 695-824 aa cytoplasmic domain. CD156b is a multi-domain protein that includes a Zn-dependent protease domain in the extracellular portion. It releases the soluble forms of TNF and TGFa from cells. CD156b was identified by its ability to cleave the transmembrane form of TNF between Ala-76 and Val-77 to generate the soluble form.
Alternative splicing yields 2 different isoforms. CD156b has an alternatively spliced message, which encodes a form lacking virtually the entire cytoplasmic domain has been identified.
CD156b has 6 N-linked glycosylation sites in the catalytic and disintegrin-cysteine-rich domains. The pro-domain is removed primarily by a cleavage after Arg-214.
|Membrane TNFα and TGFα are substrates for CD156b.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD156b
|CD156b cleaves transmembrane forms of TNFα and TGFα to generate soluble forms. As TNFα is a major mediator of inflammation and CD156b has a major role in inflammation and CD156b is essential for its release from cells. In all situations studied, CD156b is present on the cell surface constitutively but the amount on the surface decreases markedly after cells have been exposed to phorbol ester for about an hour. The cells of CD156b bear a deletion in the catalytic domain release TNFα, TGFa, and a number of other proteins very inefficiently. CD156b knockout mice display several phenotypes in common with those observed in mice lacking TGFa. It is also found to release the soluble form of this factor. It appears to shed a number of proteins as well, including L-selectin and the p75 TNF receptor, in at least some circumstances. The functions of its disintegrin-cysteine-rich domain between the catalytic domain and the membrane and its cytoplasmic domain are not known.|
Members of the ADAM family are structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development and neurogenesis. The protein encoding CD156b functions as a TNF-α converting enzyme, binds mitotic arrest deficient 2 protein and also plays a prominent role in the activation of the Notch signaling pathway.
The primary protease releases the soluble forms of TNFα and TGFa from cells.
DISEASE RELEVANCE AND FUNCTION OF CD156b IN INTACT ANIMAL
Perinatal lethality is observed in the majority of mice homozygous for a targeted mutation that deletes a region of CD156b that is critical for catalytic activity. Deletion of a catalytic domain causes perinatal death. Several phenotypes observed in CD156b-deficient mice resemble those observed in mice homozygous for naturally occurring or targeted mutations in TGFa, 1 of 6 known ligands for the epidermal growth factor receptor (EGFR). Although TGFa deficiency does not result in perinatal lethality, targeted mutations in EGFR result in embryonic lethality due to a number of epithelial lineage defects. Similar epithelial lineage defects are observed in CD156b-deficient fetuses. CD156b is essential for the release of TNF which is a critical mediator of inflammation. The potential role for CD156b in inflammation in generating soluble TNFα in vivo, has not been directly tested due to the perinatal lethality of the deletion. Expression by chondrocytes in arthritic joints may release TNF, exacerbating disease. CD156b is a possible target for anti-inflammatory and anti-arthritis therapeutics.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD156b: No information.
ENZYMES WHICH MODIFY CD156b: No information.
CD156b-mediated shedding is stimulated by a variety of agents including phorbol esters, but the mechanism of upregulation is unknown. It has been hypothesized that the disintegrin domain has an adhesive function with respect to other cells, extracellular matrix, or substrates.
Database accession numbers
Revised June 25, 2008