ADAM15 (A Disintegrin And Metalloproteinase 15) Gene
A comprehensive guide to the ADAM15 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | ADAM15 |
|---|---|
| Full Name | ADAM metallopeptidase domain 15 |
| Gene Type | protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 8751 ncbi.nlm.nih.gov/gene/8751 |
| Ensembl ID | ENSG00000143553 |
| UniProt ID | Q13444 |
| OMIM ID | 605548 |
| HGNC ID | 193 |
| Aliases | MDC15, ADAM metallopeptidase domain 15 |
Description
ADAM15 (A Disintegrin And Metalloproteinase domain 15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin And Metalloproteinase) family. It is a multi-domain protein that possesses both metalloproteinase and disintegrin domains, enabling it to function in proteolytic ectodomain shedding of cell surface proteins and in cell-cell and cell-matrix adhesion. ADAM15 is widely expressed and is involved in various physiological and pathological processes, including development, inflammation, and cancer. Its expression is often dysregulated in tumors, where it can promote cell migration, invasion, and angiogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | ADAM15 is overexpressed in many cancers (e.g., breast, prostate, lung, gastric). It promotes tumor progression by cleaving growth factors, cytokines, and adhesion molecules, thereby enhancing cell proliferation, migration, invasion, and angiogenesis. It also contributes to a tumor-promoting microenvironment. | High expression correlates with poor prognosis in multiple cancer types (e.g., breast, gastric, prostate). Functional studies show that ADAM15 knockdown reduces tumor growth and metastasis in xenograft models. (Source: NCBI Gene, UniProt, COSMIC) |
| Osteoarthritis | ADAM15 is expressed in chondrocytes and synovial tissue. It is involved in the degradation of cartilage extracellular matrix components, such as type II collagen and aggrecan, contributing to the pathogenesis of osteoarthritis. | Elevated ADAM15 expression is found in osteoarthritic cartilage compared to normal cartilage. Studies in ADAM15 knockout mice show reduced cartilage degradation in models of osteoarthritis. (Source: NCBI Gene, UniProt) |
| Inflammatory Diseases | ADAM15 is involved in the shedding of adhesion molecules and cytokines, which can modulate inflammatory responses. It may play a role in conditions like atherosclerosis and rheumatoid arthritis. | ADAM15 is expressed in atherosclerotic plaques and inflamed synovium. It can cleave substrates like E-cadherin and TNF-alpha, influencing leukocyte extravasation and inflammation. (Source: NCBI Gene, UniProt) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.7 | Medium |
| Kidney | 10.2 | Medium |
| Prostate | 9.8 | Medium |
| Breast | 8.5 | Low |
| Colon | 7.9 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 15.3 | High expression; associated with invasive phenotype. |
| MCF7 (Breast Carcinoma) | 8.2 | Moderate expression; role in cell migration. |
| PC3 (Prostate Carcinoma) | 11.5 | High expression; linked to metastasis. |
| HCT116 (Colorectal Carcinoma) | 7.1 | Moderate expression; involved in cell adhesion. |
| HEK293 (Embryonic Kidney) | 6.5 | Basal expression; used for recombinant studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.154G>A (p.Val52Ile) | Missense | Rare (<0.01%) | Located in the pro-domain; potential effect on protein processing or maturation. Clinical significance is unknown. |
| c.739C>T (p.Arg247Trp) | Missense | Rare (<0.01%) | Located in the metalloproteinase domain; may affect catalytic activity. Clinical significance is unknown. |
| c.1123A>G (p.Thr375Ala) | Missense | Rare (<0.01%) | Located in the disintegrin domain; may affect integrin binding. Clinical significance is unknown. |
| c.1876G>A (p.Asp626Asn) | Missense | Rare (<0.01%) | Located in the cytoplasmic tail; may affect intracellular signaling. Clinical significance is unknown. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ADAM15 are not well characterized in human disease. However, studies in knockout mice suggest that loss of ADAM15 can lead to reduced tumor angiogenesis and altered cartilage homeostasis, indicating a role in these processes.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported for ADAM15. However, overexpression of the wild-type protein is frequently observed in cancers and is associated with increased tumor aggressiveness, suggesting that increased ADAM15 activity can contribute to oncogenic processes.
Dominant Negative (DN)
No dominant-negative mutations have been described for ADAM15. The protein functions as a monomer, and the presence of a mutant subunit is unlikely to interfere with the function of the wild-type protein in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity | • integrin binding |
| • protein binding | • zinc ion binding |
| • extracellular matrix organization | • cell adhesion |
| • proteolysis | • cell migration |
| • angiogenesis | • membrane |
Pathways
• Integrin Signaling Pathway
• Proteoglycans in cancer
• Pathways in cancer
• Rap1 signaling pathway
• Focal adhesion
Protein Summary
The ADAM15 protein is a type I transmembrane glycoprotein composed of several domains: an N-terminal signal peptide, a pro-domain, a metalloproteinase domain, a disintegrin domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. The metalloproteinase domain is responsible for cleaving extracellular matrix components and cell surface proteins (ectodomain shedding). The disintegrin domain binds to integrins, mediating cell-cell and cell-matrix adhesion. Through these dual functions, ADAM15 plays a critical role in cell signaling, migration, and tissue remodeling. It is synthesized as a zymogen and requires cleavage of its pro-domain for activation. The cytoplasmic tail contains signaling motifs that can interact with intracellular proteins, further modulating its function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM15 Knockout HEK293 Cell Line | EDJ-KQ6350 | Human | 8751 | Details Get a Quote |
| ADAM15 Knockout A-549 Cell Line | EDJ-KQ28989 | Human | 8751 | Details Get a Quote |
| ADAM15 Knockout HCT 116 Cell Line | EDJ-KQ30300 | Human | 8751 | Details Get a Quote |
| ADAM15 Knockout HeLa Cell Line | EDJ-KQ30301 | Human | 8751 | Details Get a Quote |
