Human Gene ADAM17 (ENST00000310823.8) Description and Page Index
Description: Homo sapiens ADAM metallopeptidase domain 17 (ADAM17), mRNA. (from RefSeq NM_003183) RefSeq Summary (NM_003183): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: GQ402545.1, SRR3476690.934797.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000310823.8/ ENSP00000309968.3 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END## Gencode Transcript: ENST00000310823.8 Gencode Gene: ENSG00000151694.14 Transcript (Including UTRs) Position: hg38 chr2:9,488,486-9,555,830 Size: 67,345 Total Exon Count: 19 Strand: - Coding Region Position: hg38 chr2:9,490,177-9,555,605 Size: 65,429 Coding Exon Count: 19
ID:ADA17_HUMAN DESCRIPTION: RecName: Full=Disintegrin and metalloproteinase domain-containing protein 17; Short=ADAM 17; EC=188.8.131.52; AltName: Full=Snake venom-like protease; AltName: Full=TNF-alpha convertase; AltName: Full=TNF-alpha-converting enzyme; AltName: CD_antigen=CD156b; Flags: Precursor; FUNCTION: 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. Also involved in the activation of Notch pathway (By similarity). CATALYTIC ACTIVITY: Narrow endopeptidase specificity. Cleaves Pro- Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26- kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains. COFACTOR: Binds 1 zinc ion per subunit. SUBUNIT: Interacts with MAD2L1, MAPK14 and MUC1. INTERACTION: Q13257:MAD2L1; NbExp=3; IntAct=EBI-78188, EBI-78203; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. 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. INDUCTION: In arthritis-affected cartilage. 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). DOMAIN: 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. PTM: The precursor is cleaved by a furin endopeptidase (By similarity). PTM: 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. DISEASE: Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]. NISBD is 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. SIMILARITY: Contains 1 disintegrin domain. SIMILARITY: Contains 1 peptidase M12B domain. WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha- converting enzyme entry; URL="http://en.wikipedia.org/wiki/Tumor_Necrosis_Factor_Alpha_Converting_Enzyme";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P78536
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.