ADAM17

GeneName

ADAM17

Summary

ADAM17, also known as TACE (TNF alpha converting enzyme) or ADAM-17, is a 93 kDa transmembrane protein that plays a crucial role in the proteolytic processing of various membrane proteins, including cytokines and receptors. It is predominantly expressed at the cell surface and is localised to various cellular components such as the plasma membrane, Golgi membrane, and endoplasmic reticulum lumen. ADAM17 is involved in multiple biological pathways, including the regulation of inflammation through the cleavage of tumour necrosis factor (TNF) and the processing of Notch receptors, which are vital for cell signalling. Additionally, it participates in cell adhesion and migration processes, particularly through its interactions with integrins and other cell surface proteins, impacting B cell differentiation and T cell chemotaxis.

Importance

ADAM17 is relevant to: - Inflammatory responses due to its role in TNF processing, influencing various immune pathways. - Cancer biology through its involvement in the shedding of growth factor receptors, which can affect tumour growth and metastasis. - Neurodegenerative diseases as it is implicated in the processing of amyloid precursor protein, potentially influencing Alzheimer’s disease pathology. - Cardiovascular health through its regulation of endothelial cell migration and vascular remodelling, which are critical in atherosclerosis and other vascular diseases.

Top Products

For researchers investigating ADAM17, we recommend two excellent primary antibodies that cater to different experimental needs. The first is the well-cited polyclonal antibody, Anti-ADAM17 antibody (ab39162), which has garnered 55 citations and is particularly effective for immunohistochemistry (IHC). This product is a trusted choice for those requiring reliable detection of ADAM17 in tissue samples. Additionally, we offer the recombinant antibody, Anti-ADAM17 antibody [EPR24095-50] (ab307269), which has been validated in knockout models and is suitable for flow cytometry (FC). This recombinant option provides the advantage of batch-to-batch consistency, making it an ideal choice for researchers who prioritise reproducibility in their experiments. Together, these antibodies provide a comprehensive toolkit for studying ADAM17 across various applications. The Recombinant Human ADAM17 protein ELISA Kit (ab282373) is a reliable option for researchers looking to measure ADAM17 levels in their experiments, supported by existing literature.

Abcam Product Citation Summary

The data indicates that ADAM17 is frequently studied in human cell lines, particularly in the context of neurobiology and macrophage function. The use of Western blotting and immunoprecipitation suggests a focus on protein expression and regulation mechanisms, highlighting its relevance in various biological processes.

Abcam Product Citation Table

Domain

Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity).

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Function

Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammation and immunity (PubMed:24226769, PubMed:24227843, PubMed:28060820, PubMed:28923481). Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:36078095, PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells. Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:28923481).

Involvement in disease

Inflammatory skin and bowel disease, neonatal, 1

NISBD1

A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

The precursor is cleaved by a furin endopeptidase.

Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Phosphorylation at Thr-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding.

Tissue Specificity

Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney. Expressed in natural killer cells (at protein level) (PubMed:24337742).

Cellular localization

• Cell membrane
• Single-pass type I membrane protein

Alternative names

CD156b, CSVP, TACE, ADAM17, Disintegrin and metalloproteinase domain-containing protein 17, ADAM 17, Snake venom-like protease, TNF-alpha convertase, TNF-alpha-converting enzyme

Database links

swissprot:P78536 omim:603639 entrezGene:6868

Other research areas

• Immuno-oncology