ADAM17

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature protease. The encoded protease functions in the ectodomain shedding of tumor necrosis factor-alpha, in which soluble tumor necrosis factor-alpha is released from the membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands. The encoded protein also plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. [provided by RefSeq, Feb 2016]

ADAM Metallopeptidase Domain 17

Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. 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. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2. 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.

Amyloid precursor protein catabolic process
B cell differentiation
Cell adhesion
Cell adhesion mediated by integrin
Cell motility
Cellular response to high density lipoprotein particle stimulus
Defense response to Gram-positive bacterium
Epidermal growth factor receptor signaling pathway
Germinal center formation
Membrane protein ectodomain proteolysis
Membrane protein intracellular domain proteolysis
Negative regulation of cold-induced thermogenesis
Negative regulation of inflammatory response to antigenic stimulus
Negative regulation of transforming growth factor beta receptor signaling pathway
Neutrophil mediated immunity
Notch receptor processing
Notch signaling pathway
Positive regulation of blood vessel endothelial cell migration
Positive regulation of cell growth
Positive regulation of cell migration
Positive regulation of cell population proliferation
Positive regulation of cellular component movement
Positive regulation of chemokine production
Positive regulation of cyclin-dependent protein serine/threonine kinase activity
Positive regulation of epidermal growth factor-activated receptor activity
Positive regulation of G1/S transition of mitotic cell cycle
Positive regulation of leukocyte chemotaxis
Positive regulation of protein phosphorylation
Positive regulation of T cell chemotaxis
Positive regulation of transforming growth factor beta receptor signaling pathway
Positive regulation of tumor necrosis factor-mediated signaling pathway
Positive regulation of vascular endothelial cell proliferation
Protein processing
Proteolysis
Receptor transactivation
Regulation of mast cell apoptotic process
Response to drug
Response to hypoxia
Response to lipopolysaccharide
Spleen development
T cell differentiation in thymus
Tumor necrosis factor-mediated signaling pathway
Wound healing, spreading of epidermal cells

Membrane

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.

Extracellular: 215-671 aa
Helical: 672-692 aa
Cytoplasmic: 693-824 aa

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.