ADAM17
ADAM Metallopeptidase Domain 17
Gene Information Card
| Symbol | ADAM17 |
|---|---|
| Full Name | ADAM Metallopeptidase Domain 17 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p25.1 |
| NCBI Gene ID | 6868 ncbi.nlm.nih.gov/gene/6868 |
| Ensembl ID | ENSG00000151694 |
| UniProt ID | P78536 |
| OMIM ID | 603639 |
| HGNC ID | 195 |
| Aliases | TACE, ADAM18, CD156b, CSVP, NISBD, ADAM17 |
Description
ADAM17 (ADAM Metallopeptidase Domain 17) encodes a transmembrane metalloproteinase that functions as a sheddase, cleaving membrane-bound proteins such as TNF-alpha, Notch receptors, and EGFR ligands. It plays critical roles in cell signaling, development, inflammation, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer Disease | ADAM17-mediated cleavage of APP influences amyloid-beta production; reduced activity may increase risk. | ClinVar, OMIM |
| Inflammatory Bowel Disease | Loss-of-function variants impair TNF-alpha shedding, leading to immune dysregulation. | OMIM, NCBI |
| Neonatal Inflammatory Skin and Bowel Disease (NISBD) | Biallelic loss-of-function mutations cause severe skin and intestinal inflammation. | OMIM, ClinVar |
| Cancer (multiple types) | Overexpression or altered shedding of EGFR ligands promotes tumor growth and metastasis. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 31.2 | High |
| Placenta | 25.8 | High |
| Spleen | 22.1 | High |
| Brain | 8.5 | Medium |
| Liver | 6.3 | Medium |
| Skeletal Muscle | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 28.4 | High expression |
| HeLa | 19.7 | Moderate expression |
| A549 | 15.3 | Moderate expression |
| K562 | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.184G>A (p.Gly62Arg) | Missense | Rare | Loss of function; associated with NISBD |
| c.1072C>T (p.Arg358Trp) | Missense | Rare | Reduced sheddase activity; linked to IBD |
| c.1685A>G (p.Asn562Ser) | Missense | 0.01% | Uncertain significance |
| c.2023_2024insA | Frameshift | Very rare | Loss of function; severe NISBD |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause neonatal inflammatory skin and bowel disease (NISBD) due to impaired TNF-alpha and Notch shedding.
Gain of Function (GOF)
Not well documented; overexpression in cancers may lead to increased EGFR ligand shedding and tumor progression.
Dominant Negative (DN)
Rare; some missense variants may interfere with dimerization or substrate recognition.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity | • tumor necrosis factor receptor binding |
| • integrin binding | • membrane protein ectodomain proteolysis |
| • Notch signaling pathway | • positive regulation of cell migration |
Pathways
• TNF signaling pathway (KEGG: hsa04668)
• Notch signaling pathway (KEGG: hsa04330)
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
• Alzheimer disease (KEGG: hsa05010)
Protein Summary
ADAM17 (TACE) is a 824-amino acid transmembrane metalloproteinase with a prodomain, catalytic domain, disintegrin domain, and cytoplasmic tail. It cleaves multiple cell surface proteins, including TNF-alpha, Notch receptors, and EGFR ligands, thereby regulating inflammation, cell proliferation, and development. Its activity is controlled by prodomain removal and by the endogenous inhibitor TIMP3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM17 Knockout HEK293 Cell Line | EDC07796 | Human | 6868 | Details Get a Quote |
| ADAM17 Knockout A-549 Cell Line | EDC08118 | Human | 6868 | Details Get a Quote |
| ADAM17 Knockout HCT 116 Cell Line | EDJ-KQ18679 | Human | 6868 | Details Get a Quote |
| ADAM17 Knockout HeLa Cell Line | EDJ-KQ18680 | Human | 6868 | Details Get a Quote |
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