ADAM33: A Disintegrin and Metalloproteinase Domain 33
Key genetic factor in asthma and airway remodeling
Gene Information Card
| Symbol | ADAM33 |
|---|---|
| Full Name | ADAM metallopeptidase domain 33 |
| Gene Type | protein-coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 80332 ncbi.nlm.nih.gov/gene/80332 |
| Ensembl ID | ENSG00000149418 |
| UniProt ID | Q9BZ11 |
| OMIM ID | 607114 |
| HGNC ID | 206 |
| Aliases | ADAM 33, C20orf153, disintegrin and metalloproteinase domain-containing protein 33 |
Description
ADAM33 (ADAM metallopeptidase domain 33) encodes a member of the ADAM (a disintegrin and metalloproteinase) family. This transmembrane protein is involved in cell-cell and cell-matrix interactions, shedding of cell surface proteins, and proteolysis. ADAM33 is strongly associated with asthma and airway hyperresponsiveness, and its variants are linked to accelerated decline in lung function. The protein is expressed in smooth muscle cells, fibroblasts, and epithelial cells of the lung.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | ADAM33 variants increase susceptibility to airway hyperresponsiveness and remodeling; altered metalloproteinase activity affects extracellular matrix turnover. | OMIM 607114; NCBI Gene; multiple GWAS studies |
| Chronic Obstructive Pulmonary Disease (COPD) | Polymorphisms in ADAM33 are associated with reduced lung function and COPD risk, likely through similar airway remodeling mechanisms. | NCBI Gene; ClinVar |
| Bronchial Hyperresponsiveness | Specific SNPs (e.g., rs2280091, rs528557) correlate with increased bronchial reactivity independent of atopy. | OMIM; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 8.2 | Medium |
| Smooth Muscle | 12.5 | High |
| Fibroblasts | 6.8 | Medium |
| Trachea | 7.1 | Medium |
| Small Intestine | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung epithelial) | 5.6 | Moderate expression |
| BEAS-2B (bronchial epithelial) | 7.3 | Higher expression |
| HLF (lung fibroblast) | 9.1 | High expression |
| HASMC (airway smooth muscle) | 11.2 | Very high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2280091 (T1) | missense (Met>Thr) | 0.15 (European) | Associated with asthma susceptibility; may alter protein stability |
| rs528557 (S2) | intronic | 0.20 (European) | Linked to airway hyperresponsiveness |
| rs3918396 (V4) | missense (Val>Ile) | 0.08 (European) | Potential effect on metalloproteinase activity |
| rs2787094 | intronic | 0.12 (European) | Associated with lung function decline in COPD |
Mutation functional classification
Loss of Function (LOF)
Not clearly established; some missense variants may reduce proteolytic activity.
Gain of Function (GOF)
Hypothesized for certain asthma-associated variants, but not confirmed.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ADAM-mediated ectodomain shedding
• Extracellular matrix remodeling
• Cell adhesion and migration
Protein Summary
ADAM33 is a 813-amino acid transmembrane protein with a prodomain, metalloproteinase domain, disintegrin domain, cysteine-rich region, and EGF-like domain. It is synthesized as a zymogen and activated by furin cleavage. The metalloproteinase domain can cleave extracellular matrix components and cell surface proteins, while the disintegrin domain mediates cell-cell interactions. ADAM33 is predominantly expressed in mesenchymal cells of the lung and is implicated in airway remodeling in asthma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM33 Knockout HEK293 Cell Line | EDJ-KQ8774 | Human | 80332 | Details Get a Quote |
| ADAM33 Knockout HeLa Cell Line | EDJ-KQ57328 | Human | 80332 | Details Get a Quote |
| ADAM33 Knockout A-549 Cell Line | EDJ-KQ65834 | Human | 80332 | Details Get a Quote |
| ADAM33 Knockout HCT 116 Cell Line | EDJ-KQ74259 | Human | 80332 | Details Get a Quote |
